Ecological Research Series
FEASIBILITY OF USING BACTERIAL STRAINS
(MUTAGENESIS) TO TEST FOR ENVIRONMENTAL
CARCINOGENS
invironmenta! Research Laboratory
Office of Research and Development
U.S. Environmental Protection Agency
Gulf Breeze, Florida 32561
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RESEARCH REPORTING SERIES
Research reports of the Office of Research and Development, U.S. Environmental
Protection Agency, have been grouped into nine series. These nine broad cate-
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vironmental technology. Elimination of traditional grouping was consciously
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The nine series are:
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3. Ecological Research
4. Environmental Monitoring
5. Socioeconomic Environmental Studies
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This report has been assigned to the ECOLOGICAL RESEARCH series. This series
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This document is available to the public through the National Technical Informa-
tion Service, Springfield, Virginia 22161.
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EPA-600/3-78-CW2
APRIL 1978
FEASIBILITY OF USING BACTERIAL STRAINS (MUTAGENESIS)
TO TEST FOR ENVIRONMENTAL CARCINOGENS
by
John E. Evans
Department of Biology
University of Houston
Houston, Texas 77004
Grant No. R-804586
Project Officer
Al W. Bourquin
Environmental Research Laboratory
Gulf Breeze, Florida 32561
ENVIRONMENTAL RESEARCH LABORATORY
OFFICE OF RESEARCH AND DEVELOPMENT
U.S. ENVIRONMENTAL PROTECTION AGENCY
GULF BREEZE, FLORIDA 32561
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DISCLAIMER
This report has been reviewed by the Environmental Research
Laboratory, Gulf Breeze, U.S. Environmental Protection Agency, and
approved for publication. Approval does not signify that the contents
necessarily reflect the views and policies of the U.S. Environmental
Protection Agency, nor does mention of trade names or commercial products
constitute endorsement or recommendation for use.
ii
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FOREWORD
The protection of our estuarine and coastal areas from damage caused
by toxic organic pollutants requires that regulations restricting the intro-
duction of these compounds into the environment be formulated on a sound
scientific basis. Accurate information describing dose-response relation-
ships for organisms and ecosystems under varying conditions is required.
The Environmental Research Laboratory, Gulf Breeze, contributes to this
information through research programs aimed at determining:
0 the effects of toxic organic pollutants on individual species and
communities of organisms;
0 the effects of toxic organics on ecosystem processes and
components ;
0 the significance of chemical carcinogens in the estuarine and
marine environments.
A great deal of information has been published concerning the
presence of carcinogens in the environment. This report compiles and
evaluates reports dealing with mutagenesis testing techniques and their use
in screening for chemical carcinogens.
lomas W. Duke
Laboratory Director
Environmental Research Laboratory
Gulf Breeze, FL 32561
iii
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ABSTRACT
A rapidly growing store of data is available relative to the potential
mutagenicity and carcinogenicity of new products or chemical substances
manufactured for commerce in recent years. Literature regarding mixtures,
such as chemical wastes, however, is scarce and hard to find.
A literature review was undertaken to assess feasibility of using
bacteria as screening agents to detect environmental carcinogens.
Mutagenicity data were included in the study because growing experimental
evidence indicates that most chemical carcinogens are mutagens, and many
mutagens may be carcinogens.
This investigation found that bacterial mutagenesis can be used to
initiate a series of studies designed to screen for potential mutagens and
carcinogens in mixed chemical wastes.
This report was submitted in fulfillment of Grant No. R-804586 by the
University of Houston under partial sponsorship of the U. S. Environmental
Protection Agency. This report covers the period 15 June 1976 to 14 April
1977. Work was completed as of 1 May 1977.
iv
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CONTENTS
Foreword iii
Abstract iv
Tables vi
1. Introduction 1
2. Conclusions 2
References 18
Appendices
A. Partial List of Persons Concerned with the
Monitoring of Waters - Ames Testing. ... 24
B. Partial List of Persons Concerned with
Environmental Monitoring 28
C. Partial List of Persons Concerned with
Screening Mixed Chemical Wastes for
Mutagenic or Carcinogenic Activity . . . .32
D. Selected References Concerned with Mutagenesis
as a Screening Tool . 35
Microbiol Assay Systems for Environmental
Carcinogens and/or Mutagens 35
Other Assay Systems for Environmental
Carcinogens and/or Mutagens 81
Reports, Letters and Workshops 91
Evaluation of Assay Systems for Environmental
Carcinogens and/or Mutagens 95
Miscellaneous 101
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TABLES
Number Page
1 Microbiol assay system for mutagens and carcinogens. 3
2 Genetic lesions detected by various test systems . . 5
3 Correlation of animal carcinogenicity and bacterial
mutagenicity with and without metabolic activation . 7
4 Response in the six short-term tests to eight
carcinogenic and non-carcinogenic pairs 9
5 Percentage of accurate predictions for 58 carcinogens
and 62 non-carcinogens in six short-term tests ... 10
6 Potential mutagens and/or carcinogens in complex
mixtures 11
7 Some considerations in choosing a study design to
evaluate potential mutagens and/or carcinogens in
mixed chemical wastes 15
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SECTION 1
INTRODUCTION
We can no longer treat environmental mutagenicity and/or
carcinogenicity as an irrelevance (Bridges, 1972).
Prevention of disease is one of the most powerful motivations for
improving the environment; and among the growing roster of environmental
diseases, one is beginning to emerge as predominant: cancer (Commoner,
1975).
The purpose of this study was to assess from the literature the
feasibility of using bacterial mutants in a screening test for carcinogens in
mixed chemical wastes, sometimes associated with the occurrence of cancer
in man, e.g., petrochemical effluents (IARC MONOGRAPHS, X:12, 1976).
The rationale for including mutagenicity data in the study is based on
the growing volume of experimental evidence indicating that most chemical
carcinogens are mutagens, and many mutagens may be carcinogens. But,
whatever the exact correlation between carcinogenicity and mutagenicity may
be, the connection is of highly practical significance in that mutagenicity
testing procedures are used and have a demonstrated predictive value for
chemically induced carcinogenicity (IARC MONOGRAPHS, XI:21, 1976; Ames,
1974; Ames, 1972).
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SECTION 2
CONCLUSIONS
LITERATURE REVIEW
An urgency attached to the comparatively new and growing field of
chemical and genetic toxicology renders duplication of research a waste and
a hazard. A real need exists for literature relative to chemical mutagenicity
and carcinogenicity to be readily available in -a concise and systematic
format in publications devoted to that area of study (Wassom, 1973; Wassom
and Mailing, 1976).
The Environmental Mutagenicity Information Center, formed in 1969,
reports that literature in this field is found in approximately 2000 different
periodicals and publications. In its on-going attempt to collect, store, and
provide infromation by improved methods, the Center gained the services of
the Oak Ridge National Laboratory's Computer Center "Name Match" program
(Wassom et al., 1976; Sobels et al., 1976).
Among the journals devoted primarily to mutagenicity and carcino-
genicity is MUTATION RESEARCH, ENVIRONMENTAL MUTAGENICITY AND
RELATED SUBJECTS, REVIEWS IN GENETIC TOXICOLOGY, and GENETIC
TOXICITY AND TESTING. Varied related information, providing insight
into the numerous methods and analyses available for use in detecting and
enumerating environmental mutagens, is presented in the four volumes of
CHEMICAL MUTAGENS: PRINCIPLES AND METHODS FOR THEIR
DETECTION. The International Agency for Research on Cancer (IARC),
Lyon, France, reports its findings regarding the properties and potential
carcinogenicity of specific chemical substances in IARC MONOGRAPHS.
Microbiol Mutagenicity Assay Systems
Epidemiological studies document man's increasing exposure to mutagens
and potential carcinogens. Analyses contribute this increase to pollution
from chemicals, chemical by-products, and naturally occurring substances in
the environment. The genetic hazards associated with this building
environmental crisis require a re-thinking of the old and development of
new attitudes and methods for detection and assessment (Legator,
Zimmering, and Connor, 1976; SCAND. REV., 1976).
The framework for testing and evaluation of chemical mutagens and/or
potential carcinogens is guided by three general principles:
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1) No chemical mutagen and/or carcinogen shall be used or released
in the environment if a satisfactory substitute exists.
2) The extent of screening procedures should be related to the
degree to which man is likely to be exposed.
3) Mutagens and/or carcinogenic substances may be used with
appropriate safety measures if the benefits are judged to outweigh
the hazards. (Adapted from Bridges, 1974)
A variety of assay systems has been developed for detecting chemical
mutagens and/or carcinogens, but few have been validated. Table 1 is a
partial listing of microbiol assay systems (Miller and Miller, 1971).
TABLE 1. MICROBIQL ASSAY SYSTEM
FOR MUTAGENS AND/OR CARCINOGENS3
Test System
Reference
Salmonella typhimurium (Ames)
Salmonella typhimurium (host-mediated)
E. coli (Bridges)
E. coli (T4 bacteriophage)
E. coli (prophage induction)
B_. subtilis (transforming DNA)
B. subtilis (inhibition)
B_. subtilis (spores)
Klebsiella pneumoniae
Ames, Lee and Durston.
PROC. NAT. ACAD. SCI., 70,
782-786, 1973.
Legator and Mailing. CHEM.
MUTAGENS: PRIN. METHODS
THEIR DETECTION, 2, 569-
589, 1971.
Bridges. LAB. PRACT., 21,
413-419, 1972.
Hartman, et al., SCIENCE 172,
1058-1060, 1971.
Goldschmidt, Miller and Matney,
MICROS. GENET. BULL., 41,
3-4, 1976.
Freese and Strack. PROC.
NAT. ACAD. USA, 48, 1796-
1803, 1962.
Kada. MUTAT. RES., 38, 34,
1976.
MacGregor and Sacks. MUTAT.
RES., 38, 271-286, 1976.
Kramers, Knaap and Voogd.
MUTAT. RES., 31, 65-68,
1975. ~
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TABLE 1. MICROBIOL ASSAY SYSTEMS (cont.)
Test System
Reference
Citobacter freundii
Dictyostelium discoideum
Streptomyces coelicolor
Saccharomyces cerevisiae
Saccharomyces cerevisiae
Saccharomyces pombe
Aspergillus nidulans
Neurospora crassa
Drosophila
Kramers, Knaap and Voogd.
MUTAT. RES., 31, 65-68,
1975.
Liwerant and Pereira Da Silva.
MUTAT. RES., 33, 135-146,
1975.
Carere, et al., MUTAT. RES.,
38, 136, 1976.
Parry. LAB PRACT., 21, 417-
419, 1972.
Chambers. SCIENCE, 83, s!3,
1976.
Loprieno. MUTAT. RES., 29,
237, 1975.
Kafer, Marshall and Cohen.
MUTAT. RES., 38, 141, 146,
1976.
de Serres. CHEM. MUTAGENS.
PRIN. METHODS THEIR DETEC-
TION, 2, 311, 342, 1971.
Zimmering. ANN. N.Y. ACAD.
SCI., 269, 26-33, 1975.
Drosophila is included because it is sensitive and inexpensive.
A comparison of various types of genetic lesions induced by mutagens
and/or carcinogens and detected by various assay procedures is presented
in Table 2 (Legator, Zimmering, and Connor, 1976).
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TABLE 2. GENETIC LESIONS DETECTED BY VARIOUS TEST SYSTEMS
Mutations
Forward Specific
and/ or loci
reverse (multiple)
Systems
Hicrobial
a . Procaryote
1. S. typhimurium
2. E. eoli
b . Fungal
1. Neurospora
2. Aspergillus
3. Yeast
Plant
a. Vicia
b. Tradescantia
Insects
a. Drosophila
b. Habrobracon
c. Bombyx
In vitro mammalian
cell systems
a. Chinese hamster
b. Mouse lymphoma
In vivo mammaliam systems
a. Mouse
b. Rat
Man
X
X
X
X X
X X
X
X X
X X
X X
X
X
X
Chromosomal aberrations
Dominant Trans-
lethal location
X
X
X
X X
X
X
X
X X
X X
X X
Deletions
and
duplica-
tions
X
X
X
X
X
X
X
X
X
Nondis-
j unction
X
X
X
X
X
X
X
X
X
Induced Test sys-
recombi- terns for
nation detectomg
metabolites
X
X
X
X
X X
X X
X
X
X
* From Legator, Zimmering and Connor, 1976.
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Table 3 (McCann et al., from Bridges, 1976) is of particular interest
with respect to the relationship between carcinogenicity and mutagenicity.
Eighty-seven and seven-tenths percent of all carcinogens were detected as
positive in the Salmonella system. Using E. coli, Rosenkranz showed 85%
of the carcinogens tested to be positive (Rosenkranz, 1976).
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TABLE 3. CORRELATION OF ANIMAL CARCINOGENICITY AND BACTERIAL
WITH AND WITHOUT METABOLIC ACTIVATION
Group of compounds
Aromatic amines, etc.
Alkyl halides, etc.
Polycyclic aromatics
Esters, epoxides, carbamates, etc.
Nitro aromatics and heterocycles
Miscellaneous organics
Nitrosamines
Fungal toxins and antibotics
Mixtures (cigarette smoke condensate)
Miscellaneous heterocycles
Miscellaneous nitrogen- compounds
Azo dyes and diazo compounds
Common laboratory biochemicals
Total
Carcinogens
detected as
bacterial mutagens
23/25
17/20
26/27
13/18
28/28
1/6
20/21
8/9
1/1
1/4
7/9
11/11
-
157/178
Non-carcinogens
not mutagenic
to bacteria
10/12
1/3
7/9
5/9
1/4
13/13
2/2
5/5
-
7/7
2/4
2/3
46/46
101/117
MUTAGENICITY
Compounds of
uncertain carcinogenicity
detected as mutagens
5/7
1/1
1/1
0/1
0/2
0/1
1/1
-
-
-
-
3/3
-
11/17
a McCann et al., from Bridges, 1976.
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Purchase et al. (1976) evaluated six short-term carcinogenicity tests.
Their results are presented in Tables 4 and 5. They "clearly establish that
the Ames test and the cell transformation assay are both able to detect a
high percentage of a wide range of carcinogens."
8
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TABLE 4. RESPONSE IN THE SIX SHORT-TERM TESTS TO EIGHT
CARCINOGENIC AND NON-CARCINOGENIC PAIRS3
Ames Cell Rabin's Subcu- Sebaceous Tetra- Animal
test trans- test taneous gland zolium carcino-
Test compound formation implants suppression reduction genicity
4-Nitroquinoline-N-oxide + + + + + + +
3-Methyl-4-nitroquinoline-N-oxide -
Benzidine + + + + - +
3,3',5,5'-Tetramethylbenzidine + - -
2-Acetylaminofluorene + + + - +
4-Acetylaminofluorene + b b b -
9,10-Dimethylanthracene + + - + + + +
Anthracene - - + -
Dimethylcarbamoyl chloride + + - + + +
Dimethylformamide - - - -
l-Fluoro-2,4-dinitrobenzene + + - + + - +
1,3-Dinitrobenzene - +
p-Naphthylamine + - + - + + +
Ot-Naphthylamine - - -
Nitrosofolic acid + + + - - +
Diphenylnitrosamine + + +
Number of pairs correctly identified 8724 5 3
a From Purchase et al., 1976.
b Not tested
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TABLE 5. PERCENTAGE OF ACCURATE PREDICTIONS FOR 58
CARCINOGENS AND 62 NON-CARCINOGENS
IN SIX SHORT-TESTS3
1
2
3
4
5
6
1
2
3
4
5
6
CARCINOGENS
Ames test
Cell transformation
Rubin's test
Subcutaneous implants
Sebaceous gland suppression
Tetrazolium reduction
NON-CARCINOGENS
Ames test
Cell transformation
Rubin's test
Subcutaneous implants
Sebaceous gland suppression
Tetrazolium reduction
Per Cent
91
91
71
37
67
40
93
97
71
95
64
73
From Purchase et al., 1976.
One method of environmental screening for mutagens and/or
carcinogens involves the use of different bacterial strains to detect specific
changes in the DNA. The assessment of mutagenic and/or carcinogenic
activity by bacterial mutagenesis may be carried out in one of three ways
or combinations thereof: a) without activation by liver homogenates, b) by
activation with liver homogenates, and c) in a host-mediated assay. Such
tests as a and b are relatively quick, easy, and inexpensive methods to
indicate whether "an agent is a mutagen and/or potential carcinogen.
Green, Muriel, and Bridges (1976) found a modified Luria-Delbruck
fluctuation test of value when an increase in sensitivity is required to
detect mutagens and/or potential carcinogens.
It appears that no bacterial system by itself will be an ideal test for
any one substance, but that one system may complement another, e.g.,
Ames test (Salmonella) and Bridges (E. coli). Further, the testing proce-
10
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dures may be expanded. For example, in the three-tier approach to muta-
genicity and/or carcinogenicity screening, a substance shown in initial
testing to be positive or negative is further evaluated in other assay
systems on a quantitative basis related to its potential risk to man; in other
words, a hazard or benefit assessment (Bridges, 1974).
Microbiol Mutagenicity Assay Systems for Mixed Chemical Wastes
Currently, most mutagenic and/or carcinogenic test systems have been
used to assay selected chemicals and/or groups of pure chemicals for their
potential hazardous effects (McCann et al., 1975; McCann and Ames, 1976;
and Epstein and Legator, 1971). Attention to assessment of mixed chemical
wastes is overdue (Clive, 1977). It appears to be-a new problem area that
has been slow to develop (de Serres, 1977).
Table 6 lists some types of complex mixtures that were screened for
mutagenic and/or carcinogenic substances.
TABLE 6. POTENTIAL MUTAGENS AND/OR
CARCINOGENS IN COMPLEX MIXTURES
Nature of Mixture
References
Atmospheric Mutagens
Food Additives
Natural Substances
Oil Spills
Fishbein, L. CHEM. MUTA-
GENS: PRIN. METHODS THEIR
DETECT. 4, 219-319, 1976.
Newell, G., 1977.
communication.
Personal
Brusick, D., 1977. Personal
communication.
Butterworth, B. E., 1977. Per-
sonal communication.
Shahin, M. M. and R. C. von
Borstel. MUTAT. RES., 38,
215-374, 1976.
Clark, A. M. MUTAT. RES.,
32, 361-374, 1976.
Clark, C. H. MUTAT. RES.,
31, 63-64, 1975.
Payne, J. F. SCIENCE, 196:
10, 1977.
11
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TABLE 6. (Cont.)
Nature of Mixture
References
Marine Environment
Products of Synthetic Fuels
(EDC tar)
*Mixed Chemical Wastes (effluents)
Cigarette Smoke Condensates
Parry, J. M., D. J. Tweats
and M. A. J. Al-Mossawi.
NATURE, 364: 538-540, 1976.
Rao, T. K., et al. Eighth
Annual Meeting Environ.
Mutagen Soc., 47-48, 1977.
Rubin, I. B., et al. ENVIRON.
RES., 12, 358-365, 1976.
Epler, J. L. Proc. Symp.
Management of Residuals from
Synthetic Fuels Production,
1976.
Epler, J. L. Eighth Annual
Meeting Environ. Mutagen Soc.,
47, 1977.
Commoner, B., 1977. Personal
communication.
Vithayathil, A., 1977. Personal
communication.
Terraso, M., 1977. Personal
communication.
Commoner, B. In IDENTIFI-
CATION AND ANALYSIS OF
ORGANIC POLLUTANTS IN
WATER. Edited by L. H.
Keith. Ann Arbor: Ann Arbor
Science, 1977.
Vithayathil, A., 1977. Personal
communication.
Commoner, B., Chem. Congress
paper, 1975.
Kier, L. D., E. Yamasaki and
B. N. Ames. PROC. NAT.
ACAD. SCI. USA, 71, 4159-
4163, 1974.
*The prime interest of this study
12
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TABLE 6. (Cont.)
Nature of Mixture
References
Urine and Blood
Urine
Soot
Tar Sands
Hutton, J.J., and C. Hackney.
CANCER RES., 35, 2461-2468,
1975.
Bock, F. G., A. P. Swain and
R.L. Stedman. J. NAT. CANCER
INST., 49, 477-483, 1972.
Kubota, H., W. H. Griest, and
M. R. Guerin. Paper at the
9th Conf. Trace Substances in
Environ. Health, 1975.
Wynder, E.L. and D. Hoffman.
BR. J. CANCER 24, 574-587,
1970.
Wynder, E. L. and G. Wright
CANCER, 10, 255-271, 1957.
Legator, M. S., T. H. Connor
and M. Stoeckel. SCIENCE,
188, 1118-1119, 1975.
Legator, M.S., T. Connor and
M. Stoeckel. ANN. N.Y. ACAD.
SCI., 269, 16-20, 1975.
Legator, M. S., M. Stoeckel
and T. Connor. MUTAT. RES.,
26, 456, 1974.
Durston, W. E., and B. N.
Ames. PROC. NAT. ACAD.
SCI. USA, 71, 737-741, 1974.
Commoner, B., 1977. Personal
communication.
Tilly,. W. G., 1977. Personal
communication.
von Borstel, R. C., 1977.
Personal communication.
13
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TABLE 6. (Cont.)
Nature of Mixture
References
Vinyl Chloride Industry Waste Products
Hair Dyes
Flame Retardants
Waters
Rannug, U., and C. Ramel.
MUTAT. RES., 38, 113, 1976.
Mohn, G. R., and F. J. de
Serres. MUTAT. RES., 38,
116-117, 1976.
Shafer, N., and R.W. Shafter.
N. Y. ST. J. MED., 76, 394-
396, 1976.
Ames, B. N., H. O. Kammen
and E. Yamasaki. PROC.
NAT. ACAD. SCI. USA, 72,
2423-2427, 1975.
Prival, M.J., et al. SCIENCE,
195, 76-78, 1977.
Blum, A., and B. N. Ames.
SCIENCE 195, 17-23, 1977.
McCann, J. See Appendix A.
In the Ames test system (Ames et al., 1973), three factors limit the
detection of chemical mutagens: 1) the concentration of the mutagen and/or
potential carcinogen is too low compared to the amount of inert material in
the mixed waste, 2) the mixed waste contains toxic agents that kill the
genetic indicator organism and prevent the growth of mutant colonies, and
3) the mixture contains a concentration of histidine which interferes with
the scoring of histidine revertants when Salmonella typhimurium strains are
used (Bartsch, 1977). The second and third limitations can be overcome
by appropriate fractionation procedures and the first, partially by concen-
tration methods. The results presented in Table 6 have taken these points
into account in most cases, e.g., fractionation (Epler, 1976 in Rubin et al.,
1976).
In this connection, Clark (1977) raises two questions: 1) Do
synergistic or antagonistic reactions complicate the situation in testing
mixed wastes? 2) Do detoxification processes occur in mixed chemical
wastes? To these a third might be added: Do conversion processes occur
in mixed wastes, e.g., conversion of non-carcinogens to carcinogens?
In dealing with mixtures, Parry (1977) reports the liquid fluctuation
test to be of greater value than the plate assay, but recommends a
microbiol screen consisting of both a plate assay using Salmonella and a
liquid fluctuation test in E. coli.
14
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Marquardt and Siebert (1977) emphasize the importance of a basic
philosophy in prescreening for carcinogenicity. They suggest:
1) It has not been possible to develop a single method that will give
full information about the genetic activity of a substance.
2) It has not been possible to develop a battery of mutagenicity
tests that can be used in every single case schematically.
3) It is important to test both dimensions of mutational events:
a) The chromosomal-level induction of chromosome aberrations.
i i
b) The molecular-level induction of definite types of molecular
mutations.
Table 7 lists considerations to study design for the screening of mixed
chemical wastes.
TABLE 7. SOME CONSIDERATIONS IN CHOOSING A STUDY
DESIGN TO EVALUATE POTENTIAL MUTAGENS AND/OR
CARCINOGENS IN MIXED CHEMICAL WASTES
1. Establish a basic research philosophy for prescreening for mutagens
and/or carcinogens, e.g., standardization. (Marquardt and Siebert,
1977)
2. Is the prescreening concerned with a fractionated or unfractionated
mixed waste? e.g., protocol to be used. (Tilly, 1977; Clark, 1977)
3. Determine the toxicity and/or solubility of the substance, e.g., kind
of test to be used.
4. Is a specific mutagen known to be present or is the test being carried
out as a screening assay without prior suspicion as to the nature of
the substance? e.g., kind of test to be used. (Clark, 1977)
5. Consider the pharmacokinetics of the substance. (Marquardt and
Siebert, 1977).
6. Is screening to be limited to the Ames test or is it to be extended
with complimentary test, fluctuation tests, tier analysis, e.g., in
the case of negatives and false positives. (Parry, 1977; Bridges,
1977; Green, Muriel and Bridges, 1976)
7. Arrange for disposal of hazardous materials: TAKE ADEQUATE
SAFETY MEASURES. (Tarr, 1977; Matney. 1977).
15
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PREDICTIVE VALUE OF SHORT TERM MUTAGENICITY/CARCINOGENICITY
TESTING
At least five distinct considerations must be taken into account in
evaluating the potential hazard of a substance: 1) Is the substance
mutagenic and/or carcinogenic? 2) Is the agent likely to be mutagenic
and/or carcinogenic to man? 3) What dose of the mutagen and/or
carcinogen is being received, or will likely be received at a risk to the
population or individual? 4) What is the risk of exposure to the substance?
5) What is the acceptable risk? (Bridges 1971)
Answers to these questions cannot be obtained by short term testing
alone. The recognition of problems relative to short term testing led
Bridges (1974) to propose a tier system of testing (de Serres, 1976a).
On the other hand, it has been reported recently that short-term
testing has a high predictive value in assaying for mammalian carcinogens.
Purchase (1976) states that the Ames test and a cell transformation assay
are both sufficiently sensitive to carcinogenicity.
The predictive value of short-term tests, including assays in microbiol
systems, had been discussed widely (Legator and Zimmering, 1975; Dean,
1976; McCann et al., 1975; McCann and Ames, 1976; Sobels, 1976; Rochkov
et al., 1976; Bartsch, 1976; Purchase, 1976; Matter, 1976; de Serres,
1976b; Bridges, 1976a, b).
SUMMARY
This study has noted the debate and salesmanship active in the
growing field of genetic toxicology. However, the growing awareness and
world-wide concern over this problem are refreshing.
Increased research aimed at improvements and conveniences for man,
not least of which are new energy sources, is proliferating new substances
that enter the environment in the form of marketable products or disposable
wastes. A rapidly growing store of data is available relative to the
potential mutagenicity and/or carcinogenicity of given products or
substances, but literature dealing with work on mixtures, such as chemical
wastes, is difficult to find.
Testing of mixed chemical wastes should focus on: 1) a long-range
objective--to establish a screen sufficiently sensitive (toward 100%) to detect
potential mutagens and/or carcinogens; 2) a short-range objective—to
design an inexpensive tool that can be used to reduce pollution, even as
little as 20% (Terraso).
Intensive study should be undertaken concerning numerous potentially
hazardous mixtures being released in the environment in voluminous
quantities each day from untold numbers of known and unknown sources.
16
-------
This monumental task could begin with experimentation using the Ames
test, which has been validated as relatively easy, quick and an inexpensive
method.
It is difficult to select a specific mutagenicity test appropriate for
pre-screening pure substances. Choosing an assay system for mixed
substances is involved. Particular data regarding a test gives it greater
relevance than another in a given situation, i.e., those systems which a)
permit the identification of the nature of induced genetic changes and b)
demonstrate that the change is transmitted to subsequent generations.
Mutagenicity testing using organisms that are well understood genetically,
e.g., Escherichia coli, Salmonella typhimurium, Saccharomyces and
Drosophila, meet the requirements outlined here. (IARC MONOGRAPHS XI:
22, 1976).
This study has found it feasible to use bacterial mutagenesis to initiate
a series of studies designed to screen for potential mutagens and/or
carcinogens in mixed chemical wastes.
17
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18
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Green, M. H. L., W. J. Muriel and B. A. Bridges. Use of a
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Hartman, P. E., et al. Hycanthone:
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A Frameshif t Mutagen.
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IARC MONOGRAPHS. EVALUATION OF CARCINOGENIC RISK OF
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EVALUATION OF CARCINOGENIC RISK OF
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20
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41. Kafer, E., P. Marshall and G. Cohen. Well-marked Strains of
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42. Kier, L. D., E. Yamasaki and B. N. Ames. Detection of Mutagenic
Activity in Cigarette Smoke Condensates. PROC. NAT. ACAD. SCI.
USA, LXXI: 4159-4163, 1974.
43. Kramers, P. G. N., A. G. A. C. Knaap and C. E. Voogd. Lack of
Mutagenicity of Chlormequat Chloride in Drosophila and in Bacteria.
MUTAT. RES., XXXI: 65-68, 1975.
44. Kubota, H., W. H. Griest and M. R. Guerin. Determination of
Carcinogens in Tobacco Smoke and Coal-derived Samples-trace Poly-
nuclear Aromatic Hydrocarbons. Presented to Ninth Conference on
Trace Substances in Environmental Health, Columbia, Missouri, June 9,
1975.
45. Legator, M. S., T. H. Connor and M. Stoeckel. Detection of
Mutagenic Activity of Metronidazole and Niridazole in Body Fluids of
Humans and Mice. SCIENCE, CLXXXVIII: 1118-1119, 1975.
46. Legator, M. S., T. Connor and M. Stoeckel. The Detection of
Mutagenic Substances in the Urine and Blood of Man. ANN. N. Y.
ACAD. SCI., CCLXIX: 16-20, 1975.
47. Legator, M. S., and H. V. Mailing. The Host-mediated Assay, a
Practical Procedure for Evaluating Potential Mutagenic Agents in
Mammals. CHEM. MUTAGENS: PRIN. METHODS THEIR DETECT., II:
569-589, 1971.
48. Legator, M. S., M. Stoeckel and T. Connor. Techniques for Isolating
Mutagenic Substances From Urine and Blood of Treated Mammals Using
Histidine Auxotrophs of Salmonella typhimurium as the Indicator
Organism. MUTAT. RES., XXVI: 456, 1974.
49. Legator, M. S., and S. Zimmering. Integration of Mammalian,
Microbial and Drosophila Procedures for Evaluating Chemical Mutagens.
MUTAT. RES., XXIX: 181-188, 1975.
50. Legator, M. S., S. Zimmering and T. H. Connor. The Use of Indirect
Indicator Systems to Detect Mutagenic Activity in Human Subjects and
Experimental Animals. CHEM. MUTAGENS: PRIN. METHODS THEIR
DETECT., IV: 171-191, 1976.
51. Liwerant, I. J., and L. H. Pereira Da Silva. Comparative Mutagenic
Effects of Ethyl Methane-Sulfonate, N-methyl-N'-nitro-N-nitrosoguani-
dine, Ultraviolet Radiation and Caffeine on Dictyostelium discoideum.
MUTAT. RES., XXXIII: 135-146, 1975.
21
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52. Loprieno, N., et al. The Use of Yeast Systems in Environmental
Mutagenesis. MUTAT. RES., XXIX: 237, 1975.
53. MacGregor, J. T., and L. E. Sacks. The Sporulation of Bacillus
sub tills as the Basis of a Multigene Mutagen Screening Test. MUTAT.
RES., XXXVIII: 271-286, 1976.
54. Matter, B. E. Problems of Testing Drugs for Potential Mutagenicity.
MUTAT. RES., XXXVIII: 243-258, 1976.
55. McCann, J., and B. N. Ames. Detection of Carcinogens as Mutagens
in the Salmonella/microsome Test. Assay of 300 Chemicals:
Discussion. PROC. NAT. ACAD. SCI. USA, LXXIII: 950-954, 1976.
56. McCann, J., and B. N. Ames. The Salmonella/microsome Mutagenicity
Test: Predictive Value for Animal Carcinogenicity. To appear in
ORIGINS OF HUMAN CANCER, PROC. OF THE CONFERENCE. New
York: Cold Spring Harbor Laboratory, 1976.
57. McCann, J., et al. Detection of Carcinogens as Mutagens in the
Salmonella/microsome Test: Assay of 300 Chemicals. PROC. NAT.
ACAD. SCI. USA, LXII: 5135-5139, 1975.
58. McCann, J., et al. Taken from Bridges, B. A., Short Term
Screening Test for Carcinogens. NATURE, CCLXI: 195-200, 1976.
59. Miller, E. C., and J. A. Miller. The Mutagenicity of Chemical
Carcinogens: Correlations, Problems and Interpretations. CHEM.
MUTAGENS: PRIN. METHODS THEIR DETECTION, I: 83-119, 1971.
60. Mohn, G. R., and F. J. de Serres. On The Mutagenic Activity of
Hair Dyes. MUTAT. RES., XXXVIII: 116-117, 1976.
61. Parry, J. M., Mitotic Recombination in Yeast as a Test of Genetic
Damage. LAB. PRACT., XXI: 417-419, 1972.
62. Parry, J. M., D. J. Tweats and M. A. J. Al-Mossawi. Monitoring the
Marine Environment for Mutagens. NATURE, CCCLXIV: 538-540, 1976.
63. Payne, J. F. Oil spills: Effects of Petroleum on Marine Organisms.
SCIENCE, CXCVI: 10, 1977.
64. Prival, M. J., et al. Tris (2,3-dibromopropyl) Phosphate: Mutagenicity
of a Widely Used Flame Retardant. SCIENCE, CXCV: 76-78, 1977.
65. Purchase, I. F. H., et al. Evaluation of Six Short Term Tests for
Detecting Organic Chemical Carcinogens and Recommendations for Their
Use. NATURE, CCLXIV: 624-627, 1976.
66. Rannug, U., and C. Ramel. The Mutagenicity of Waste Products from
the Vinyl Chloride Industries. MUTAT. RES., XXXVIII: 113, 1976.
22
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67. Rao, T. K., et al. Correlation of Mutagenic Activity of Energy
Related Effluents with Organic Constituents. PROC. EIGHTH ANNUAL
MEETING ENVIRON. MUTAGEN SOC., 47-48, 1977.
68. Rosenkranz, H. S. Cited in Bridges, B. A, Short Term Screening
Tests for Carcinogens. NATURE, CCLXI: 195-200, 1976.
69. Rubin, I. B., et al. Fractionation of Synthetic Crude Oils from Coal
for Biological Testing. ENVIRON. RES., XII: 358-365, 1976.
70. Shafer, N., and R. W. Shafer. Potential of Carcinogenic Effects of
Hair Dyes. N. Y. ST. J. MED., 394-396, 1976.'
71. Shahin, M. M., and R. C. von Borstel. Genetic Activity of the Anti-
microbial Food Additives Af-2 and H-193 in Saccharomyces cerevisiae.
MUTAT. RES., XXXVIII: 215-224, 1976.
72. Sobels, F. H., Some Thoughts on the Evaluation of Environmental
Mutagens. MUTAT. RES., XXXVIII: 361-366, 1976.
73. Sobels, F. H., et al. The New Section of Mutation Research. Genetic
Toxicology Testing. MUTAT. RES., XL: 1-2, 1976.
74. Wassom, J. S. The Literature of Chemical Mutagenesis. CHEM.
MUTAGENS: PRIN. METHODS THEIR DETECT., Ill: 271-287, 1973.
75. Wassom, J. S., and H. V. Mailing. Suggested Format for Articles to
be Submitted to "Genetic Toxicology Testing," MUTAT. RES., XL:
3-8, 1976.
76. Wassom, J. S., et al. Specialized Information Center in Toxicology.
I. Environmental Mutagen Information Center. In Legator, M. S., et
al. FIRST ANNUAL COURSE IN THE PRIN. PRACT. GENETIC
TOXICOL., University of Texas Medical Branch, Galveston, Texas,
1976.
77. Wynder, E. L., and D. Hoffmann. The Epidermis and the Respiratory
Tract as Bioassay Systems in Tobacco Carcinogenesis. BR. J.
CANCER, XXIV: 574-587, 1970.
78. Wynder, E. L., and G. Wright. A Study of Tobacco Carcinogens. I.
The Primary Fractions. CANCER, X: 255-271, 1957.
79. Zimmering, S. Utility of Drosophila for Detection of Potential Environ-
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1975.
23
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APPENDIX A
PARTIAL LIST OF PERSONS
CONCERNED WITH THE MONITORING
OF WATERS - AMES TESTING
(Prepared by Dr. Joyce'McCann)
People Interested in Mutagenicity of Water Resources
(Rivers, Lakes, Drinking Water, Waste Water etc.)
Person
Argardy, Dr. Franklin
Vice President, URS Corp.
155 Bovet Road
San Mateo, CA 94402
Asketh, Dr. Phoebe
Environmental Research and
Technology, Inc.
696 Virginia Road
Concord, MA 01742
Butler, Dr. Janis
Analytical & Research Chemists
and Biologists
Wilson Laboratories
631 East Crawford
P. O. Box 28
Salina, KA 67401
Chriswell, Dr. Colin D.
Assistant Chemist II
316 Metallurgy
Ames Laboratory, Department of
Energy
Iowa State University
Ames, IA 50011
Area of Interest
Consulting firm on pollution
Detection of mutagens in air
and water environments
Drinking water analyses;
industrial waste
Analysis of water concentrates
using GC mass spectrophoto-
meter
24
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Clowes, Dr. Royston C.
Department of Biology
The University of Texas at Dallas
Box 688
Richardson, TX 75080
Fordham, Dr. W. D.
Associate Professor of Chemistry
Farleigh Dickinson University
Teaneck-Hackensack Campus
Teaneck, NJ 07666
Gough, Dr. Michael
Assistant Professor
Department of Microbiology
School of Basic Health Sciences
Health Sciences Center
State University of New York
Stony Brook, NY 11794
Grabow, Dr. Wilhelm O. K.
National Institute for Water
Research
Council for Scientific and
Industrial Research
P. O. Box 395
Pretoria 0001, South Africa
Kelly, Mr. Thomas J. Jr.
59 Tyler Street
Hyde Park, MA 02136
Kpol, Dr. H.
Rifksinstitut voor Drinkwater-
voorziening
Parkweg 13
Den Hague, The Netherlands
McCormick, Dr. Neil G.
Research Microbiologist
Biotechnology Group
Food Sciences Laboratory
Department of the Army
U.S. Army Natick Research and
Development Command
Natick, MA 01760
Moore, Dr. Richard L.
Faculty of Medicine
Division of Pathology
The University of Calgary
2920 24 Avenue N.W.
Calgary, Canada T2N 1N4
Efficiency of local water
purification and mutagenic
effects of chloramine
treatment
Detection and isolation of
carcinogens from Hackensack
River
Analysis of storm water
runoffs, sewage
Water analysis
Fresh water testing; frog
mutations
Detection and isolation of
carcinogens in drinking
water
Biodegrade nitroaromatics
from H2O discharges
Water quality study -- rivers
in Alberta, Canada
25
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Ogg, Dr. James E.
College of Veterinary Medicine
and Biomedical Sciences
Department of Microbiology
Colorado State University
Fort Collins, CO 80523
Pelon, Dr. William
Department of Tropical Medicine
and Medical Parasitology
Louisiana State University Medical Center
1542 Tulane Avenue
New Orleans, LA 70112
Poppel, Mr. David
Graduate Research Assistant
Department of Botany
The University of Massachusetts
Amherst, MA 01002
Roberts, Ms. Lesley Joyce
Research Assistant
Indiana Public Interest Research
Group of Bloomington, Inc.
703 East 7th
Bloomington, IN 47401
SOi.)sey, Dr. Mark
Assistant Professor of Environ-
mental Microbiology
Department of Environmental
Sciences and Engineering
The School of Public Health
The University of North Carolina
Chapel Hill, NC
Stang, Mr. William J.
Chief, Microbiology Section
Environmental Protection Agency
Office of Enforcement
National Enforcement Investigations
Center
Building 53, Box 25227
Denver Federal Center
Denver, CO 80225
Star key, Mr. Roland J. Jr.
Graduate Student
Ecology Laboratory
Room 308, Disque Hall
Department of Biological Sciences
Drexel University
Philadelphia, PA 19104
Mutagenic chemicals in waste
water
Detection of carcinogens in
water samples
Detection of mutagens in
river water
Water quality in regional
water resources
Detection of mutagens/
carcinogens in water and
wastewater
Mutagens/carcinogens in
water
Occurrence of mutagenic
agents in the aquatic
environment
26
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Stewart, Mr. Ken
c/o Dr. Leah Koditschek
Department of Microbiology
Montclair State College
State of New Jersey
Upper Montclair, NJ 07043
Tardiff, Dr. Robert G.
Executive Director
Board on Toxicology and Environ-
mental Health Hazards
National Academy of Sciences/
National Research Council
2101 Constitution Avenue, N.W.
Washington, D.C. 20418
Wilson, Dr. John E.
School of Public Health and
Community Medicine
Department of Environmental
Health, SC-34
University of Washington
Seattle, WA 98195
Recovery and viability of E.
coli in polluted estuarine
sediment. Assay for muta-
genic activity with Salmonella/
Microsome test
Mutagenic activity of drinking
water concentrates
Water analysis
27
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APPENDIX B
PARTIAL LIST OF PERSONS
CONCERNED WITH ENVIRONMENTAL MONITORING
(Prepared by Dr. William R. Lower)
Laboratory
Abrahamson, Dr-. S.
Department of Zoology
University of Wisconsin
Madison, WI 53706
Bartling, Mr. G.
Cancer Research Center
P. O. Box 1268
Columbia, MO 65201
Bishop, Dr. Jack
Division of Mutagenesis
National Center for Toxicological
Research
Mail Code 8
Jefferson, AK 72079
DeMarini, Dr. D. M.
Department of Biological Sciences
Illinois State University
Normal, IL 69761
Epler, Dr. James L.
Unit Leader, Biology Division
Oak Ridge National Laboratory
Oak Ridge, TN 37830
Evans, Dr. John E.
Department of Biology
University of Houston
Houston, TX 77004
Area of Interest
Drosophila, mutagenesis
testing
Salmonella: environmental
Development and validation of
mutagenesis protocols-proving
animal dose and response data
Water of lakes and cigarette
smoke. Lower eucaryotes
as test systems.
Microbial system, Drosophila,
mammalian cells
Ames testing of mixed chemical
wastes
28
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Fevers, Mr. Ritchie
Division of Mutagenesis
National Center for Toxicological
Research
Mail Code 8
Jefferson, AK 72079
Flessel, Dr. Peter
Environmental Biochemistry Group
Air and Industrial Hygiene
Laboratory
California State Department of
Health
2151 Berkeley Way
Berkeley, CA 94704
Franklin, Dr. Ralph
Soil Scientist
Environmental Programs
Division of Biomedical and Environ-
mental Research
Department of Energy
Washington, DC 20545
Gentile, Dr. J. M.
Department of Biological Sciences
Hope College
Holland, MI 49423
Grant, Dr. William F.
Genetics Laboratory
MacDonald Campus of McGill
University
Ste. Anne de Belleone
Quebec, Canada HOA ICO
Hardigree, Dr. Alice
Biology Division
Oak Ridge National Laboratory
P. O. Box Y
Oak Ridge, TN 37830
Hooper, Dr. Kim
Department of Biochemistry
University of California
Berkeley, CA 94704
Johnson, Dr. F. M.
Chemistry and Life Sciences
Division
Research Triangle Institute
Research Triangle Park, NC 27709
Ames assay, air and industrial
samples, heavy metal muta-
genesis
Changes in ecological para-
meters, particularly in energy
facilities or fuel cycles
Plant vs. animal activation
studies; mutagenesis of
naturally occurring microbial
populations
Cytogenetics of pesticides
Water, pesticides, mutagenic
and carcinogenic potency:
Salmonella system
Bioassay-environmental
analysis
29
-------
Laimer, Dr. F. W.
Biology Division
Oak Ridge National Laboratory
Oak Ridge, TN 37830
Lower, Dr. William R.
Environmental Trace Substances
Research Center
University of Missouri, Columbia
Columbia, MO 65201
Ma, Dr. Te-Hsiu
Department of Biological Science
Western Illinois University
Macomb, IL 61455
Nauman, Dr. Charles H.
Biology Department
Brookhaven National Laboratory
Upton, NY 11973
Pelroy, Dr. Richard
Battell North West
Richland, WA 99352
Plewa, Dr. Michael J.
100 Environmental Research
Laboratory
Institute for Environmental
Studies
University of Illinois
Urbana, IL 61801
Rao, Dr. T. K.
Biology Division
Oak Ridge National Laboratory
P. O. Box Y
Oak Ridge, TN 37830
Rogers, Dr. Sam
Chemistry Department
Montana State University
Bozeman, MT 59715
Sandhu, Dr. Shahbeg
Research Biologist
Health Effects Research Laboratory
Protection Agency
Research Triangle Park, NC 27711
Gene mutation and mitotic
recombination assays with
yeast applications to moni-
toring synthetic fuel
technologies
Environmental monitoring,
heavy metal mutagenesis
Tradescantia, corn, soy-
bean, Peromyscus, domestic
animals, Drosophila
Tradescantia, chromosome
damage, air and water
pollutants
Tradescantia, chemical
mutagen/physical mutagen
somatic, mutation induction
Plant activation, Zea maize
wx locus assay, pesticide
evaluation
Salmonella typhimurium, E.
coli, energy related -
environmental effluents
Chemistry of rafter dust,
Tradescantia, microbial
systems
Cellular toxicity, mutagenesis
and cellular neoplastic trans-
formation (oncogenesis)
30
-------
Schairer, Dr. Lloyd A.
Biology Department
Brookhaven National Laboratory
Upton, NY 11973
Schmidt-Collerus, Dr. Josef
Denver Research Institute
University of Denver
Denver, CO 80200
Stebbings, Dr. James H.
Health Division MS881
Los Alamos National Laboratory
Los Alamos, NM 87454
Sumner, Dr. Darrell
CIBA-GEIGY Corporation
Greensboro, NC 27420
Tomkins, Dr. Darrell J.
Department of Pediatrics
McMaster University Medical Center
Hamilton, Ontario Canada L8S 4J9
Vyse, Dr. E. R.
Department of Biology
Montana State University
Bozeman, MT 59715
•Warren, Dr. G. R.
Chemistry Department
Montana State University
Bozeman, MT 59715
Zimmering, Dr. Sam
Division of Biological and
Medical Sciences
Brown University
Providence, RI 02912
Tradescantia test system in
the lab as well as in the
mobile monitoring vehicle -
field testing
Human population studies
Pesticide metabolism
Human and plant populations
Drosophila - air monitoring,
pesticide testing
Microbial systems
Mutagenicity testing of envi-
ronmental compounds in Dro-
sophila and improvement of
techniques for mutagenicity
testing in Drosophila
31
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APPENDIX C
PARTIAL LIST OF PERSONS CONCERNED WITH
SCREENING MIXED CHEMICAL WASTES
FOR MUTAGENIC OR CARCINOGENIC ACTIVITY
(Prepared by Dr. John E. Evans)
Person
Bridges, Professor Bryn A.
Director, MRC Cell Mutation Unit
University of Sussex
Falmer, Brighton
BN1 9QG England
Brusick, Dr. David
Director, Department of Genetics
Litton Bionetics
5516 Nicholson Lane
Kensington, MD 20795
Chrisp, Dr. C. E.
Radiobiology Laboratory
University of California
Davis, CA 95616
Clark, Professor A. M.
Department of Biology
The Flinders University
of South Australia
Bedford Park, South Australia 5042
Epler, Dr. James L.
Unit Leader, Biology Division
Oak Ridge National Laboratory
Oak Ridge, TN 37830
Area of Interest
Mixtures
Air samples
Coal ash
Mixed wastes
Energy systems
32
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Lower, Professor William R. Air samples
Group Leader, Environmental
Trace Substances Research Center
University of Missouri
Route 3
Columbia, MO 65201
Ma, Professor Te-Hsiu Gaseous pollutants
Department of Biological Sciences Water solutions
Western Illinois University
Macomb, IL 61455
Parry, Professor James M. Hydro-carbon mixtures
Department of Genetics
University College of Swansea
Singleton Park
Swansea SA2 8PP, U.K.
Terraso, Dr. Michael F. Mixed chemical wastes
Laboratory Director
Harris County Pollution Control
Department
107 North Munger
Box 6031
Pasadena, TX 77506
Thilly, Professor William G. Mixed chemical wastes
Department of Nutrition and
Food Science
Rm E18-664
Cambridge, MA 02139
Tokiwa, Professor Hiroshi Air samples
Fukuoka Environmental Research
Center, 39 Mukaeda
Dazaifu-machi, Chikushi-gun
Fukuoka, 818-01, Japan
Urwin, Dr. Colin Cutting oils
Huntingdon Research Centre
Huntingdon, Cambs., U.K.
Venitt, Dr. S. Food color mixtures
Division of Chemical Carcinogenesis
Institute of Cancer Research
Pollards Wood Research Station
Nightengales Lane
Chalfont St. Giles,
Bucks, HP8 4SP, U.K.
33
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Vithayathil, Dr. Antony T- Mixed chemical wastes
Project Coordinator Air samples
Center for the Biology of Natural
Systems
Washington University
Box 1126
St. Louis, MO 63130
von Borstel, Professor R. C. Tar sands
Department of Genetics Mixed chemical wastes
The University of Alberta
Edmonton, Canada T6G 2E9
34
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APPENDIX D
SELECTED REFERENCES CONCERNED WITH
MUTAGENESIS AS A SCREENING TOOL
(Prepared by Dr. John E. Evans)
MICROBIOL ASSAY SYSTEMS FOR ENVIRONMENTAL CARCINOGENS AND/OR
MUTAGENS
Agnet, Y., J. L. Dorange and P. Dupuy
Mutagenicity of Peracetic Acid on Salmonella typhimurium. MUTAT. RES.,
XXXVIII: 119, 1976.
An abstract
Mutagenicity testing by procedure of Ames (Salmonella)
Alper, M. D., and B. N. Ames
Positive Selection of Mutants With Deletions of Gal- chl Region of the
Salmonella Chromosome as a Screening ProceduFe lor Mutagens That
Cause Deletions. J. BACT., CXXI: 259-266, 1975. 32 refs.
This paper presents a positive selection procedure for mutants with long
deletions in the gal region of the chromosomes of Salmonella typhimurium
and Escherichia cpli. The technique is of value in the screening of
mutagens lor their ability to generate long deletions in the bacterial
deoxyribonucleic acid.
Ames, B. N.
A Bacterial System for Detecting Mutagens and Carcinogens. ENVIRON.
SCI.: AN INTERDISCIPLINARY MONOGRAPH SERIES, 57-66, 1972.
12 refs.
Characteristics of the Ames Mutagenicity Test are discussed, e.g.,
simplicity, sensitivity, comprehensiveness and strain characteristics.
Mutagenicity testing procedure is given.
35
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Ames, B. N.
A Combined Bacterial and Liver Test System for Detection and Classification
of Carcinogens as Mutagens. GENETICS, LXXVIII: 91-95, 1974. 8
refs.
A general discussion paper dealing with a system for detection of mutagens
and carcinogens. They postulate that carcinogens cause cancer by
somatic mutation and suggest" that this combined detection system is a
simple procedure for detecting carcinogens.
Mutagenicity testing by procedure of Ames.
Ames, B. N., H. O. Kamman and E. Yamasaki
Hair Dyes are Mutagenic: Identification of a Variety of Mutagenic
Ingredients. PROC. NAT. ACAD. SCI. USA, LXXII: 2423-2427, 1975.
36 refs.
Hair dying chemicals are carcinogens or mutagens as shown by the S.
typhimurium tester strains.
Ames, B. N., F. D. Lee and W. E. Durston.
An Improved Bacterial Test System for the Detection and Classification of
Mutagens and Carcinogens. PROC. NAT. ACAD. SCI. USA, LXX:
782-786, 1973. 18 refs.
An imporved S. typhimurium tester strain deficient in lipopolysaccharide,
known as deep rough, has been constructed for detection of carcinogens as
mutagens.
The techniques for using the strains for detecting mutagens are shown to
be extremely sensitive and convenient. The specificity of frameshift
mutagenesis is clarified. A test is described, comparing mutagenic killing
in deep rough strains with and without DNA excision repair, and a test
using forward mutagenesis in a deep rough strain lacking excision repair.
Ames, B. N., J. McCann and E. Yamasaki.
Methods for Detecting Carcinogens and Mutagens With the Salmonella/
mammalian-microsome Mutagenicity Test. MUTAT. RES., XXXI: 347-
364, 1975. 29 refs.
Various facets of the Salmonella/mammalian microsome mutagenicity test are
described and discussed, including the standard plate test, the use and
storage of the bacterial tester strains, preparation and use of the liver
homogenates (S-9), and the methods of inducing the rats for elevated
microsomal enzyme activity. Application and interpretation of results is
discussed.
Mutagenicity testing by procedure of Ames (Salmonella).
36
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Ames, B. N., P. Sims and P. L. Grover.
Epoxides of Carcinogenic Polycylic Hydrocarbons are Frameshift Mutagens.
SCIENCE, CLXXVI: 47-49, 1972. 20 refs.
K-region epoxides of the carcinogens benz[a]anthracene, dibenz[a,h]-
anthracens, and 7-methylbenz[a]anthracene are mutagenic in strains of S.
typhimurium designed to detect frameshift mutagens. Parent hydro-
carbons , K-region diols and phenols and some other epoxides are inactive
as mutagens in these tests. Polycyclic hydrocarbon epoxides, and other
presumed proximal carcinogens, are discussed as examples of intercalating
agents with reactive side chains. It has been shown previously that
intercalating agents with reactive side chains are potent frameshift
mutagens.
Mutagenicity testing by procedure of Ames.
Ames, B. N., and H. J. Whitfield, Jr.
Frameshift Mutagenesis in Salmonella. COLD SPRING HARBOR SYMPOSIA,
XXXI: 221-225, 1966. 17 refs.
A basic discussion of frameshift mutation in Salmonella is presented,
describing ICR mutagens, a group of new acridine-like compounds which
are powerful mutagens in bacteria. Evidence is presented, suggesting
that these compounds add and/or delete nucleotides from DNA.
Mutagenicity testing by procedure of Ames.
Ames, B. N., and C. Yanofsky
The Detection of Chemical Mutagens With Enteric Bacteria. CHEM.
MUTAGENS: PRIN. METHODS THEIR DETECT., I: 267-282, 1971. 19
refs.
Any test system for mutagens should be calibrated against the known
mutagens to determine the ease and sensitivity of the test in detecting
these compounds before trying new substances. We believe bacteria are
the system of choice for mass screening of new compounds on the basis of
simplicity, sensitivity, economy, and range of compounds detected.
Characteristics of the bacterial mutagenicity test are described.
Mutagenicity testing by the procedure of Ames.
Ames, B. N., et al.
Carcinogens as Frameshift Mutagens: Metabolites and Derivatives of 2-
acetylamino Fluorene and Other Aromatic Amine Carcinogens. PROC.
NAT. ACAD. SCI. USA, LXIX: 3128-3132, 1972. 66 refs.
Certain metabolites of carcinogenic substances, 2-acetyl-aminofluorene,
nitros and derivatives of 5 other aromatic amines are frameshift mutagens.
It is suggested that carcinogens are carcinogenic as a result of a reactive
intercalation into DNA. The utility of a set of bacterial strains for
detecting carcinogens as mutagens is shown.
Mutagenicity screening by procedure of Ames.
37
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Ames, B. N., et al.
Carcinogens are Mutagens: A Simple Test System Combining Liver
Homogenates for Activation and Bacteria for Detection. PROC. NAT.
ACAD. SCI. USA, LXX: 2281-2285, 1973. 23 refs.
Carcinogens and mutagens cause cancer by somatic mutation. Eighteen
carcinogens are shown to be activated by liver homogenates, forming
potent frameshift mutations in S. typhimurium. We believe that these
carcinogens have in common a ring system sufficiently planar for a
stacking interaction with DNA base pairs and a part of the molecule
capable of being metabolized to a reactive group: these structural
features are discussed in terms of the theory of frameshift mutagenesis.
We propose that these carcinogens, and many others that are mutagens,
cause cancer by somatic mutation. A simple, inexpensive and extremely
sensitive test for detection of carcinogens as mutagens is described. It
consists of the use of a rat or human liver homogenate for carcinogen
activation and a set of Salmonella histadine mutants for mutagen detection.
The homogenate, bacteria and a TPHN-generating system are all incubated
together on a petri plate. With the most active compounds, as little as a
nanogram can be detected.
Mutagenicity testing by procedure of Ames (Salmonella).
Andrews, A. W., E. S. Zawistowski and C. R. Valentine.
A Comparison of the Mutagenic Properties of Vinyl Chloride and Methyl
Chloride. MUTAT. RES., XL: 273-276, 1976. 9 refs.
A screening program for environmental gases using the Ames assay has
shown that vinyl chloride and methyl chloride are highly mutagenic.
Mutagenicity testing by procedure of Ames.
Anton, D. N. and L. V. Orce.
Envelope Mutation Promoting Autolysis in S. typhimurium. MOLEC. GEN.
GENET., CXLIV: 97-105, 1976.
Two strains independently isolated in S. typhimurium display abnormal
autolytic activity when nutrient broth becomes alkaline. They also show
increased sensitivity to deoxycholate, EDTA, and sodium dodecly sulfate.
Response to acridine orange remains normal. In both strains a single
stable mutation is responsible for all the changes.
Mutagenicity testing by procedure of Ames.
Bamford, D., et al.
Mutagenicity and Toxicity of Amitrole. III. Microbial Tests. MUTAT.
RES., XL: 197-202,1976. 15 refs.
Amitrole inhibits bacterial growth both in E. coli and S. typhimurium at a
concentration of 0.5% in minimal medium.
38
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Mutagenicity was tested by differential growth comparisons on E. coll
strains defective in DNA polymerase I and a revertant. Known mutagens
were used as positive controls.
Mutagenicity testing by procedure of Ames.
Bardodej, Z.
Metabolic Studies and the Evaluation of Genetic Risk from the Viewpoint of
Industrial Toxicology. MUTAT. RES., XLI: 7-14, 1976. 43 refs.
The paper is concerned with important industrial chemicals, e.g., solvents,
and monomers used in the production of plastics, which have been found
to be more dangerous than had been suspected. Some of them are
mutagens and carcinogens. Mutagenicity testing by procedures of Ames
and using Drosophila is mentioned.
Bartsch, H., A. Camus and C. Malaveille.
Comparative Mutagenicity of N-nitrosamines in a Semi-Solid and in a Liquid
Incubation System in the Presence of Rat or Human Tissue Fractions.
MUTAT. RES., XXXVII: 149-162, 1976.
The rat liver microsome-mediated mutagenicities of a series of N-nitroso-
dialkylamines and heterocyclic N-nitrosamines were determined in a liquid
incubation system using S. typhimurium TA1530. The influence on
mutation frequency of the concentration of co-factors for mixed-function
oxidase and composition and molarity of the buffer was investigated,
using N-nitrosomorpholine as substrate. The mutagenicity of the N-
nitroso compounds in the liquid incubation system under optimal reaction
conditions at equimolar concentration was compared quantitatively with
that obtained in a soft-agar incorporation assay.
The plate incorporation assay is more effective in detecting chemicals whose
metabolic conversion into mutagens occurs at a low rate. Incorporation of
liver microsomal enzymes in a soft-agar layer prolongs their viability for
up to several hours.
Mutagenicity testing by procedure of Ames (Salmonella)
Bartsch, H., and R. Montesano.
Mutagenic and Carcinogenic Effects of Vinyl Chloride. MUTAT. RES.,
XXXII: 93-114, 1975. 100 refs.
The available data concerning the biological hazards of VCM show that this
compound is toxic, mutagenic and carcinogenic in man, as well as in
animals.
The mutagenic action of VCM in microbial systems has been demonstrated.
Mutagenicity testing by procedure of Ames.
Bartsch, H., et al.
Tissue-Mediated Mutagenicity of Vinylidene Chloride and 2-Chlorobutadiene
in S. typhimurium. NATURE, CCLV: 641-643, 1975. 20 refs.
39
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We have examined the mutagenicity of VDC and 2-chlorobutadiene in S.
typhimurium strains, using a tissue-mediated assay which has been found
effective in detecting the mutagenicity of various carcinogens, such as
mtrosamines, vinyl chloride and many others.
Mutagenicity testing by the procedure of Ames.
Benditt, E. P.
The Origin of Atherosclerosis. SCI. AM., CCXXXVI: 74-85, 1977. 5
refs.
The monoclonal hypothesis, which holds that the proliferating cells of an
atherosclerotic plaque all stem from one mutated cell, suggests new lines
of research on the causes of coronary disease.
Mutagenicity testing by procedure of Ames (Salmonella)
Blum, A., and B. N. Ames
Flame-Retardant Additives as Possible Cancer Hazards. SCIENCE, CXCV:
17-23, 1977. 53 refs.
The flame retardant in children's pajamas is a mutagen.
Mutagenicity testing by procedure of Ames.
Braun, R., and J. Schoneich
The Influence of Ethanol and Carbon Tetrachloride on the Mutagenic
Effectivity of Cyclophosphamide in the Host-Mediated Assay with S.
typhimurium. MUTAT. RES., XXXI: 191-194, 1975. 10 refs.
Synergistic effects of the type described here are of interest with respect
to chemical mutagenesis in man. A modern trend in medicine is the
simultaneous administration to patients of two and more drugs. Further-
more, patients may obtain and use drugs from irregular sources in
addition to those prescribed or may abuse drugs during therapeutic
treatments. In the cases described here uncontrolled potentiation of
mutagenic effects might be possible and should be taken into considera-
tion.
Mutagenicity testing by procedure of Ames.
Brem, H., A. B. Stein and H. S. Rosenkranz
The Mutagenicity and DNA-Modifying Effect of Haloalkanes. CANCER RES.,
XXXIV: 2576-2579, 9 refs.
A series of haloalkanes, some of them widely used in industry and in the
home, are shown to be mutagenic for S. typhimurium and preferentially to
inhibit the growth of DNA polymerase-~deficient E. coli. It was found that
the relative activities of the test substances differed when examined in
these systems and that one of the agents was active in the pol Aa-
system only. In view of these results it is suggested that both assays be
used in routine screening of environmental agents.
40
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Mutagenicity testing by procedure of Ames and DNA polymerase-deficient E.
coli.
Bridges, B. A.
Simple Bacterial Systems for Detecting Mutagenic Agents. LAB. PRACT.,
XXI: 413-419, 1972. 8 refs.
Bacteria may be used to detect specific types of mutational damage. Most
mutagens, however, are not very specific and a more useful system is one
that responds to a wide variety of mutagenic agents. Detailed
descriptions are given of techniques that can be used with the bacterium
E. coli WP2 which mutates from tryptophan requirement to independence.
A number of strains deficient in repair functions are available which give
useful information about the type of DNA damage and the mechanism of
mutagenesis with a particular agent.
Mutagenicity testing - E. coli.
Bridges, B. A., R. E. Dennis and R. J. Munson
Differential Induction and Repair of Ultraviolet Damage Leading to True
Reversions and External Suppressor Mutations of an Ochre Codon in E.
coli B/r WP2. GENETICS, LVII: 897-908, 1967. 28 refs.
Evidence is presented that a number of E. coli strains have chain-
terminating codons at their auxotrophic loci. They may mutate to proto-
trophy either by true reversion at the chain-terminating codon or by
mutation at suppressor loci. The two types of prototroph may be
distinguished by the ability of the latter to support growth of T4 phage
also carrying chain-terminating mutations. In E. coli B/r WP2 Try-,
which appears to have an ochre codon, both types of mutation arise
spontaneously.
Mutagenicity testing - E. coli.
Bridges, B. A., R. E. Dennis and R. J. Munson.
Mutation in E. coli B/r WP2 Try- by Reversion or Suppression of a Chain-
Terminating CocTon. MUTAT. RES., IV: 502-504, 1967. 17 refs.
We conclude from our results that E. coli B/r WP2 carries a chain-
terminating mutation, possibly an ochre (UAA codon), at one of its
tryptophan loci. Bacteria may mutate to prototrophy either by a
presumed true reversion at this locus or by an external ochre suppressor
mutation.
Mutagenicity testing - E. coli.
Bridges, B. A., J. Law and R. J. Munson.
Mutagenesis in E. coli. II. Evidence for a Common Pathway for Muta-
genesis by Ultraviolet Light, Ionizing Radiation and Thymine
Deprivation. MOLEC. GEN GENETICS, GUI: 266-273, 1968. 27 refs.
41
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Both thymine starvation and gamma radiation, like ultraviolet light, produce
base change mutations to prototrophy in E. coli and EXr+ phenotype is
involved in the mutation process. DNA strand" breakage is a direct or
indirect consequence of all three treatments suggesting that the filling of
gaps in DNA by a process involving the EXr gene product may be a
common step in mutagenesis.
Mutagenicity testing - E. coli.
Bridges, B. A., and R. P. Mottershead.
Mutagenic DNA Repair in E. coli. MOLEC. GEN. GENET., CXLIV: 53-58,
1976. 28 refs.
The POLC temperature-sensitive DNA polymerase III mutation from E. coli
BT1026 has been transduced into E. coli WP2 and WP2 WRA. In
excision-deficient CM741 UV-induced Trp+ mutations" progressively lost
their photoreversibility during post-irradiation incubation at 34°.
Immediately after transfer to 43°, however, there was no further loss of
reversibilty although post-replication strand joining still occurred and
uptake of 3H-thymidine into DNA continued for 20 to 30 min. In
excision-proficient CM731, UV lesions capable of leading to Str. mutations
disappeared during post-irradiation incubation at restrictive temperature
and there was no increase in the number remaining after exposure to
photoreversing light. In contrast, at permissive temperature, premuta-
tional lesions were not lost and became progressively converted into
non-photoreversible mutations. It is concluded that a function of the
POLC gene is necessary for error-prone repair to occur -and that this
function is defective at 43° in the enzyme specified by the POLC allele
from BT1026. This function seems not to be essential for most post-
replication or excision repair or for normal DNA replication and may be
particularly involved in the insertion of incorrect bases during error-
prone repair.
Mutagenesis testing E. coli.
Bridges, B. A., R. P. Mottershead and C. Collella.
Induction of Forward Mutations to Colicin E2 Resistance in Repair Deficient
Strains of E. coli: Experiments with Ultraviolet Light and Captan.
MUTAT. RES., XXI: 303-313, 1973. 8 refs.
The present experiments confirm the previous observation made with spot-
test technique that captan produces excisable DNA damage in bacteria
that leads to the formation of mutations via a pathway dependent upon the
EXRA+ gene.
Mutagenicity testing - E. coli.
Bridges, B. A., and R. J. Munson.
Mutagenesis in E. coli: Evidence for the Mechanism of Base Change
Mutation by~ Ultraviolet Radiation in a Strain Deficient in Excision-
repair. PROC. ROY. SOC. B., CLXXI: 213-226, 1968. 23 refs.
42
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The mutagenic action of UV radiation has been studied upon E. coli WP 2
Try HCR growing exponentially at 37°C. Although this strain is unable
to excise pyrimidine dimers from its DNA, it showed no detectable
reduction in growth rate after exposure to a dose of UV calculated to
produce several dozen pyrimidine dimers per chromosome. As judged by
photoreversibility of mutations to prototrophy, dimers at mutable sites
may persist for up to about 4 generation times after UV and may give
rise to mutations with a low probability in each replication cycle during
this period. The slow disappearance of dimers takes place whether or not
DNA replication is inhibited and indirect evidence suggests that excision-
repair may not be involved. Mutations are established only when DNA
replication is taking place and are not expressible on unsupplemented
medium until approximately one generation time after being established.
Mutagenicity testing - E. coli.
Bridges, B. A., et al.
Mutagenicity of Dichlorvos and Methyl Methane-Sulphonate for E. coli WP 2
and Some Derivatives Deficient in DNA Repair. MUTAT. RES., XIX:
295-303, 1973. 26 refs.
The mutagenic and lethal action of methyl methanesulphonate and dichlorvos
has been studied on E. coli WP 2 and some derivatives deficient in DNA
repair genes. The EXRA+ and RECA+ alleles were necessary for
significant mutagenesis by either compound, and the UVRA gene affected
neither the lethal nor mutagenic responses. Increased sensitivity to both
compounds was shown by the EXRA and VRAEXRA strains and in a more
pronounced way by the UVRA POLA, RECA and UVRAEXRAPOLA strains.
Bacteria deficient at the POLA locus were 2 and 3 times more mutable by
DDVP and MMS respectively. Single strand breaks were detectable by
alkaline sucrose gradient centrifugation after both MMS and DDVP
treatment of POLA bacteria.
Mutagenicity testing in E. coli.
Bridges, B. A., et al.
Repair-Deficient Bacterial Strains Suitable for Mutagenicity Screening:
Tests With the Fungicide Cap tan. CHEM.-BIOL. INTERACT., X:
77-84, 1972. 19 refs.
A spot test with selected repair-deficient strains of E. coli is described
which not only provides a sensitive assay for the mutagenic activity of
chemicals, but also gives useful information about the characteristics of
the mutagenic process. The production of this volatile mutagen is
greater at alkaline pH. The excisable DNA damage produced by the
mutagen does not depend on EXRA+ and RecA+ repair functions for its
mutagenicity.
Mutagenicity testing by E. coli.
43
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Brock, R. D.
Differential Mutation of the B-galactosidase Gene of E. coli. MUTAT. RES.,
XI: 181-186, 1972. 11 refs. ~
A range of mutagenic agents has been tested using the B-galactosidase
locus of E. coli. Treatment with alkylating agents diethyl sulphate, ethyl
methanesulphonate and N-methyl-N'-nitro-N-nitrosoguanidine induced a
higher frequency of mutation when applied to the active gene than when
applied to the inactive gene. X-Rays and base analogues 5-bromodeoxy-
uridine and 2-aminopurine had the same mutagenic efficiency for both
active and inactive genes.
Mutagenicity testing - E. coli.
Brown, J. P., and R. J. Brown.
Mutagenesis by 9,10-anthraquinone Derivatives and Related Compounds in
S. typhimurium. MUTAT. RES., XL: 203-224, 1976. 51 refs.
Ninety 9,10-anthraquinone derivatives and related anthracene derivatives
were screened for mutagenicity with 5 S. typhimurium tester strains with
and without mammalian microsomal activation. About 35% of the compounds
tested are considered to be mutagenic. Three patterns of mutagenesis
were apparent.
Mutagenicity testing - Procedure of Ames.
Carere, A., et al.
Mutational Studies With Some Pesticides in Streptomyces coelicolor and
Salmonella typhimurium. MUTAT. RES., XXXVIII: 136, 1976.
An abstract
Mutagenicity testing by procedure of Ames (Salmonella) and in Streptomyces
coelicolor.
Carere, A., et al.
Point Mutations Induced by Pharmaceutical Drugs. MUTAT. RES., XXIX:
235, 1975.
To rapidly test the mutagenic activity of pharmaceutical drugs, two genetic
systems have been set up in the filamentous bacterium Streptomyces
coelicolor.
An abstract.
Mutagenicity testing - S. coelicolor.
Chambers, C., and S. K. Dutta.
Mutagenic Tests- of Chlordane on Different Microbial Tester Strains.
SCIENCE, LXXXIII: s!3, 1976.
Three different microbial tester strains of Saccharomyces cereviseae D3, D4
and D5 to measure mitotic recombination and mitotic gene conversion
44
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events; and three tester strains of S. typhimurium strains TA1535, TA100
and TA1538 for detecting base-pair substitution and frameshifts were used
to test the potential mutagenic effects of chlordane, a chlorinated
cyclodiene.
Mutagenicity testing by the procedure of Ames (Salmonella) and in S.
cereviseae.
Combes, R. D.
Inability of Genetic Systems of B. subtilis to Detect a Mutagenic Effect of
Low Frequency Ultrasound. J. APPL. BACT., XXXIX: 219-226, 1975.
21 refs.
Possible mutagenic effects of low frequency ultrasound have been assessed
with genetic systems of B. subtilis. Ultrasound was unable to cause a
detectable increase in the spontaneous frequency of back-mutation irre-
spective of the degree of killing. Similar treatments were incapable of
producing mutagenic lesions that could be detected by the system of
transformation after in vitro treatment of DNA. Transforming activity
and molecular weight could be reduced without a corresponding decline
in linkage between two contiguous markers. It is concluded that muta-
genic effects of ultrasound could not be detected by these genetic
systems.
Mutagenicity assay in B. subtilis.
Commoner, B.
Chemical Carcinogens in the Environment. Paper presented at the First
Chemical Congress of the North American Continent, Mexico City,
Mexico, December 1, 1975. 8 refs.
A paper on environmental carcinogens, e.g., petrochemical effluents and air
pollutants.
Mutagenicity testing by procedure of Ames (Salmonella).
Commoner, B., A. J. Vithayathil and J. I. Henry.
Detection of Metabolic Carcinogen-fed Rats by Means of Bacterial Muta-
genesis. NATURE, CCXLIX: 850-852, 1974. 9 refs.
Thus, metabolic intermediates of AAF and DAB can be detected in the urine
of rats fed on diets that contain these carcinogens by means of tests
based on mutagenicity towards a strain of S. typhimurium, while the
urine of rats on normal diets yields no significant response in these tests.
Mutagenicity testing by procedure of Ames.
Connor, T. H., et al.
The Contribution of Metronidazole and Two Metabolites to the Mutagenic
Activity Detected in Urine of Treated Humans and Mice. CANCER
RES., XXXVII: 629-633,1977. 12 refs.
45
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The urine of two patients receiving therapeutic doses of the trichomonacide,
metronidazole, was analyzed for mutagenic activity using the histidine
auxotroph TA1535 of S. typhimurium. The activity detected in the urine
was significantly higher than could be accounted for by the presence of
the administered drug. Chromatographic analysis of the urine indicated
the presence of the metabolite, which, when tested in vitro with AT1535
was found to be ten times more active than metronidazole. An additional
urinary metabolite was found to be inactive when similarly tested. The in
vitro mutagenic activity of metronidazole and the two metabolites were
unchanged by the addition of phenobarbital-or Arclor-induced rat liver
homogenate to the test system. Metronidazole and the hydroxymethyl
metabolite reverted S. typhimurium TA100 but not TA1537, TA1538 or
TA98, and the acetic acid metabolite failed to revert any of the tester
strains. Findings using mice indicate the production of metabolites from
the parent compound by the liver of the intact animal which could not be
determined by use of the standard in vitro liver homogenate system.
Mutagenicity testing by procedure of Ames.
Corran, J.
The Induction of Supersuppressor Mutants of B. subtilis by Ethyl Methane-
sulphonate and the Posttreatment Modification of Mutation Yield.
MOLEC. GEN. GENETICS, GUI: 42-57, 1968. 24 refs.
Supersuppressor mutants have been induced in a strain of B. subtilis with
the chemical mutagen ethyl methanesulphonate. The yield of mutants
recovered is dependent on the degree of supplementation of the selective
plating medium with minute quantities of either nutrient broth or the
previously required growth supplements. The optimal quantities of these
medial additives have been established and the superiority of nutrient
broth described. This "broth effect" has been shown to be due to
components of the nutrient broth other than the previously required
growth substances.
Mutagenicity tested in B. subtilis.
Couch, D. B. and M. A. Friedman.
Interactive Mutagenicity of Sodium Nitrite, Dimethylamine, Methylurea and
Ethylurea. MUTAT. RES., XXXI: 109-114, 1975. 20 refs.
Groups of mice were treated per os with sodium nitrite either alone or in
combination with nitrosatable ammo compounds and tested in the host-
mediated assay. When mice were treated with sodium nitrite in combina-
tion with dimethylamine a small but significant increase in mutant
frequency was observed. Ethylurea or methylurea in combination with
sodium nitrite induced 10- or 850-fold increases in MF, respectively. The
response to methylurea was dose-dependent with a 6- and 30-fold increase
in MF at 5.4 and 11.5 mg/kg NaNO2 and a 6-fold increase at 108 mg/kg
methylurea. That this response reflected gastric nitrosation was shown
by the disappearance of the response if NaNO2 administration preceded
methylurea treatment by 10 min. High MF's were observed if NaNO2 was
administered 10 or 20 min. after methylurea.
Mutagenicity testing by procedure of Ames.
46
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Czy gan, P., et al.
Microsomal Metabolism of Dimethylnitrosamine and the Cytochrome P-450
Dependency of Its Activation to a Mutagen. CANCER RES., XXXIII:
2983-2986, 1973. 17 refs.
Oxidative demethylation of the secondary carcinogen dimethylnitrosamine by
the isolated mouse liver microsomes and the activation of DMN to a
bacterial mutagen showed similar kinetics. The rates of demethylation
and DMN activation increased following induction of the cytochrome P-450
mixed-function oxidase system by polychlorinated biphenyls. Both the
oxidative demethylation and the activation of DMN to a mutagen were
inhibited by carbon monoxide, and the inhibition was maximally reduced
by monochromatic light at 450 nm. These observations indicate that both
microsomal metabolism and activation of DMN to a mutagen are cytochrome
P-450 dependent.
Mutagenicity testing - procedure of Ames.
DeLuca, J. G., et al.
Comparative Mutagenicity of ICR-191 to S. typhimurium and Diploid Human
Lymphoblast. MUTAT. RES., XLVI: 11-18,,1977. 16 refs.
Concentration-dependent mutagenicity of ICR-191 has been measured in S.
typhimurium strain TA98 and in a diploid human cell line. In both cell
systems, approximately equigenerational exposure produced mutation
linearly related to concentration in the lower range of ICR-191 concen-
trations tested. Saturation behavior was observed in the human cell
assay but not in the bacterial assay. However, a 25-fold greater
concentration of ICR-191 was required to induce a significant rise in the
mutant fraction in the S. typhimurium assay than in the human cell
assay. These differences may 5e linked to the differences in the
biochemical events required for mutation or in the time of exposure to
ICR-191.
Mutagenicity testing by procedure of Ames (Salmonella).
Durston, W. E., and B. N. Ames
A Simple Method for the Detection of Mutagens in Urine: Studies With the
Carcinogen 2-acetylaminofluorene. PROC. NAT. ACAD. SCI., USA,
LXXI: 737-741, 1974. 25 refs.
The addition of commercial p-glucuronidase to the petri plates along with
the urine, liver homogenate and bacteria allows detection of metabolites
that are excreted in urine as p-glucoronide conjugates. By this method
mutagenic activity is readily demonstrated with urine of rats administered
as little as 200 ug of the carcinogen. In this case the major urinary
metabolite that is detected appears to be a glucuronide conjugate.
47
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Ellenberger, J., and G. Mohn.
More about Intrasanguineous Mutagenicity Testing. MUTAT. RES., XXIX:
235, 1975.
The usefulness of the multi-purpose strain E. coli K-12 GalRs i8/arg56/
nad113 has been investigated. A comparison ~bT the retention by the
liver between a deep rough strain of S. typhimurium is made.
An abstract.
Mutagenicity testing - E. coli and S. typhimurium.
Epler, J. L.
Comparative Mutagenesis. Biology Division, Oak Ridge National Laboratory,
Oak Ridge, Tennessee. 11 refs.
The major goal of this mutagenesis research group is to provide a means of
testing the mutagenicity of those compounds produced by various existing
or proposed methods of energy generation.
To approach the problems of testing large numbers of compounds, we set
up a form of the "tier system" utilizing Salmonella, E. coli, yeast, human
leukocytes, mammalian cells and Drosophila.
Mutagenicity testing by the procedure of Ames (Salmonella), in E. coli, in
Drosophila and in tissue culture.
Epler, J. L., et al.
Feasibility of Application of Mutagenicity Testing to Aqueous Environmental
Affluents. EIGHTH ANNUAL MEETING ENVIRON. MUTAGEN SOC.
Colorado Spring, Colorado, 1977, p. 47.
An abstract.
The Salmonella test system developed by Ames was applied as a prescreen
for ascertaining the biohazard of complex environmental aqueous effluents.
Mutagenicity testing by procedure of Ames (Salmonella)
Fahrig, R.
Development of Host-Mediated Mutagenicity Tests-Yeast Systems. II.
Recovery of Yeast Cells out of Testes, Liver, Lung and Peritoneum of
Rats. MUTAT. RES., XXXI: 381-394, 1975. 8 refs.
All studies in the host-mediated assay using yeast cells have been
performed with the diploid yeast strains D-3 and D-4 of S. cerevisiae,
suited for the observation of mitotic recombination and gene conversion.
Results underline the importance of the problem of organ-specific activity
of mutagens for the host-mediated assay in particular and mutagenicity
testing in general.
Mutagenicity testing in a yeast system (host mediated).
48
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Ficsor, G., et al.
An Organ-Specific Host-Mediated Microbial Assay for Detecting Chemical
Mutagens in Vivo: Demonstration of Mutagenic Action in Rat Testes
Following Streptozotocin Treatment. MUTAT. RES., XIII: 283-287,
1971. 8 refs.
A method is described in which tester bacteria enclosed in diffusion bags
are implanted in the testes or in the peritoneal cavities of rats subse-
quently injected with the chemical mutagen, Streptozotocin. Three hours
after Streptozotocin treatment, the bacteria are recovered and plated on
appropriate media to determine the frequency of induced mutations. The
MF among bacteria obtained from both the testes and peritoneal cavities of
streptozotocin-treated rats was manifold greater than among bacteria
obtained from control animals.
Mutagenicity testing by procedure of Ames--host mediated.
Frantz, C. N., and H. V. Mailing
The Quantitative Microsomal Mutagenesis Assay Method. MUTAT. RES.,
XXXI: 365-380, 1975. 18 refs.
Mammals can convert some non-mutagenic compounds to highly mutagenic
metabolites. Such promutagens will not be detected by mutagenicity
screening techniques which use microorganisms to detect genetic damage
unless mammalian metabolism is first allowed to act on the chemicals.
Also, the active mutagen metabolites may be short-lived, such as
alkylating agents which combine with many common chemical groups, so
that the organism must be in close spatial and temporal contact with the
metabolism of the promutagen in order to detect mutagenic activity.
Mutagenicity testing -- procedure of Ames.
Frease, E., and H. B. Strack
Induction of Mutations in Transforming DNA by Hydroxylamine. PROC.
NAT. ACAD. USA, XLVIII: 1796-1803, 1962. 23 refs.
This paper reports that the mutagenic reactivity of DNA bases is greatly
increased when the strands are partially or completely separated. Proto-
troph transforming DNA of B. subtilis was treated with HA. The
recipients were tryptophan-dependent bacteria that cannot grow on
indole. They were plated on a medium containing indole and other
nutrients required for mutant isolation, except tryptophan.
Mutagenicity testing -- B. subtilis transforming DNA.
Garner, R. C., E. C. Miller and J. A. Miller.
Liver Microsomal Metabolism of Aflatoxin B! to a Reactive Derivative Toxic
to S. typhimurium TA1530. CANCER RES., XXXII: 2058-2066, 1972.
45 refs.
49
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On the basis of the data presented, it is tentatively suggested that the
derivative that is toxic to S. typhimurium TA1530 and the one that reacts
with nucleic acids are identical. The possible relationship of this
derivative to the hepatocarcinogenicity of aflatoxin BI is discussed.
Mutagenicity testing by procedure of Ames.
Garner, R. C., A. L. Walpole and F. L. Rose.
Testing of Some Benzidine Analogues for Microsomal Activation to Bacterial
Mutagens. CANCER LETTERS, I: 39-42, 1975. 13 refs.
Analogues of benzidine were assayed for mutagenic activity towards S.
typhimurium TA1538 in the presence and absence of a liver enzyme
preparation. Purified 3,3'-dichloro-benzidme and the technical grade
material had some direct mutagenic activity, but this was increased over
50-fold by addition of a liver mixed function oxidase preparation. In the
presence of the liver preparation, 3,3'-dichlorobenzidine as approximately
10 times more active than benzidine, while SjS'^S'-tetrafluorobenzidine
was of approximately equipotency. On the other hand, S^'^S'-tetra-
mcthylbenzidine had no mutagenic activity alone or in conjunction with a
liver preparation; 3,3'-Dianisidine had slight mutagenic activity in the
presence of liver but none in its absence.
Mutagenicity testing by procedure of Ames.
Goldschmidt, E. P.. R. Miller and S. T. Matney
Induction of Prophage in a Lysogen of a Deep Rough Strain of E. coli: A
Possible Method for Detecting Carcinogens. MICROB. GENET. BULL.,
XLI: 3-4, 1976.
A brief note on a possible method for detecting carcinogens.
Mutagenicity testing and prophage induction.
Goldschmidt, E. P., et al.
Isolation of Deep Rough Mutants of E. coli Suitable for Testing Carcinogens
for Mutagenesis. MICROB. GENET. BULL., XXXIX: 19-20, 1975.
A brief note on a method used to isolate deep rough mutants of E. coli.
Mutagenicity testing in E. coli.
Grant, E. L., et al.
Mutagenicity and Putative Carcinogenicity Tests of Several Polycyclic
Aromatic Compounds Associated With Impurities of the Insecticide
Methoxychlor. MUTAT. RES., XL: 225-228, 1976. 7 refs.
Several polycyclic hydrocarbons, which are associated as impurities in
commercial samples of the insecticide methoxychlor, have been tested in
the Ames mutagenicity test with strains of S. typhimurium, TA1535,
TA1537, TA1538 and TA98. Activation by liver microsomes induced with
either phenobarbitol or Aroclor was examined. The only active compound
50
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was 3,6,11,14-tetra-methoxydibenzo (g,p)chrysene, mutagenic to strain
TA98.
Mutagenicity testing by procedure of Ames.
Green, M. H. L., and W. J. Muriel.
Mutagen Testing Using TRP+' Reversion in E. coli. MUTAT. RES.,
XXXVIII: 3-32, 1976. 25 refs.
A detailed paper discussing four ways of performing mutational screening
tests, using E. coli strain WP2: spot tests, treat and plate tests,
simplified fluctuation test and use of a liver microsomal fraction. The
merits, defects and pitfalls of the system are described. The E. coli
system is to be regarded as complimentary to the S. typhimurium test
system.
Mutagenicity testing in E. coli.
Green, M. H. L., and W. J. Muriel.
Use of Repair-Deficient E. coli Strains and Liver Microsomes to Characterize
Mutagenesis by DimetHylnitrosamine. CHEM.-BIOL. INTERACT., XI:
63-65, 1975. 10 refs.
DMN mutagenesis using suitable E. coli strains was examined. It was
confirmed that DMN is not mutagenic when incubated with liver microsomes
in soft agar, although it is mutagenic using the Mailing system of incuba-
tion with microsomes in liquid and bubbling air through the mixture.
This aeration did not seem helpful and the method described was adapted.
Mutagenicity testing in E. coli.
Green, M. H. L., W. J. Muriel and B. A. Bridges
Use of a Simplified Fluctuation Test to Detect Low Levels of Mutagens.
MUTAT. RES., XXXVIII: 33-42, 1976. 10 refs.
As a mutagen screening procedure a modification of the Luria and Delbruck
fluctuation test was used in which the individual tubes are scored by eye
for the presence or absence of a mutation.
The test is simple and extremely sensitive, detecting concentrations of
mutagens up to 100-fold lower than conventional tests.
Measuring mutation to tryptophan independence in E. coli strain WP2 it was
found that methyl methanesulphonate, mitomycin C, dichlorvos and
K2CrO4 are all positively mutagenic in the test, whereas NiCl2 is
negative. Chronic exposure to low levels of mutagens using this method
appears to induce more mutations than might be predicted.
Mutagenicity testing in E. coli.
51
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Green, M. H. L., et al.
Mutagenic DNA Repair in E. coli. V. Mutation Frequency Decline and Error-
Free Post-Replication Repair in an Excision-Proficient Strain. MUTAT.
RES., XLII: 33-44,1977. 36 refs.
Mutation frequency decline is an irreversible loss of newly-induced sup-
pressor mutations occurring in excision-proficient E. coli during a short
period of incubation in minimal medium before plating on broth or
Casamino acids-enriched selective agar.
Mutagenicity testing-- E. coli.
Guerin, M. R., and J. L. Epler.
Determining Emission Measurements Needs for an Emerging Industry-
Advanced Fossil Fuels Utilization. (Paper presented at the First
Conference on Determining Fugitive Emissions Measurements Needs,
Hartford, Connecticut, May 17, 1976). 25 refs.
The paper presents one approach to establishing reliable methods and
generating data of value in prioritizing environmental and health studies.
Measurements needs are identified through an experimental assessment of
existing methods.
Mutagenicity testing by procedure of Ames (Salmonella)
Hardigree, A. A., and J. L. Epler
Mutagenicity of Plant Flavonols in Microbial Systems. EIGHTH ANNUAL
MEETING ENVIRON. MUTAGEN SOC. Colorado Springs, Colorado,
1977, p. 48.
An abstract.
Extraction techniques yielding partially purified preparations of flavonols
from natural products are being carried out and coupled to bioassays for
mutagenic activity(s) present in the crude materials.
Mutagenicity testing by procedure of Ames (Salmonella)
Hartman, P. E., et al.
Hycanthone: A Frameshift Mutagen. SCIENCE, CLXXII: 1058-1060, 1971.
22 refs.
Rapid spot-test screening of antischistosomal agents reveals that hycanthone
is a potent frameshift mutagen while the closely related compound,
miracil D, is nonmutagenic in Salmonella. Both hycanthone and miracil D
are frameshift mutagens for T4 bacteriophage during growth in E. coli.
Mutagenicity testing in Salmonella, T4 bacteriophage - E. coli.
52
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Hauser, R., and B. E. Matter.
Localization of E. coli K-12 in Livers of Mice Used for an Intra-Anguineous
Host-Mediated Assay. MUTAT. RES., XLVI: 45-48, 1977. 7 refs.
The intrasanguineous host-mediated assay is a considerable improvement of
the technique devised for combination of mammalian metabolism and micro-
organisms for mutagenicity testing. After intravenous injection of E. coli
K-12 into rats and mice, sufficient numbers of bacteria are recoverable
from the liver within a period of 180 min to be screened for mutation
induction. Since the liver is the main organ carrying out drug-
metabolism, this method turned out to be more sensitive compared to the
intraperitoneal host-mediated assay, i.e., some mutagenic compounds are
already detectable at relatively low dose-levels.
Mutagenicity testing -- E. coli.
Herbold, B., and W. Buselmaier.
Comparative Investigations With Different Bacterial Strains. MUTAT. RES.,
XXXVIII: 118, 1976.
An abstract.
Mutagenicity testing by the procedure of Ames (Salmonella)
Herbold, B., and W. Buselmaier
Induction of Point Mutations by Different Chemical Mechanisms in the Liver
Microsomal Assay. MUTAT. RES., XL: 73-84,1976. 10 refs.
A selection of chemical agents with different mechanisms of chemical
mutability was tested with the liver microsomal assay, using different S.
typhimurium tester strains. The tested agents were all well-known
mutagens and divided as alkylating agents, anti-metabolites, acridines and
those that form radicals in the cell. All of the mutagens except
amethopterine gave positive results, showing that this system is very
sensitive.
In comparing the strains and mutagens a correlation was noted between the
diameter of the molecule and the permeability of the bacterial cell
membrane.
Mutagenicity testing by procedure of Ames (Salmonella).
Hince, T. A., and S. Neale
Physiological Modification of Alkylating-Agent Induced Mutagenesis. I.
Effect of Growth Rate and Repair Capacity on Nitrosomethyl-Urea-
Induced Mutation of E. coli. MUTAT. RES., XLVI: 1-10, 1977. 41
refs.
The effects of repair capacity and growth rate on the induction of mutations
by N-methyl-N-nitrosourea was investigated using the trpE reversion
system of E. coli WP2 and some repair-deficient derivatives isogenic for
this gene. In all these strains reducing the growth rate prior to MNUA-
53
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treatment caused a reduction in the mutational response, however major
differences were observed between strains.
Mutagenicity testing in E. coli.
Hong, J.-S. and B. N. Ames
Localized Mutagenesis of Any Specific Small Region of the Bacterial Chromo-
some. PROG. NAT. ACAD. SCI. USA, LXVIII: 3158-3162, 1971. 29
refs.
A method called localized mutagenesis is described for the isolation of
temperature-sensitive and other types of mutations in any specific small
region of the bacteral chromosome. The principle of this method is to
mutate the transducing DNA rather than the bacterial DNA. One can
select for the introduction of this mutated DNA into any particular region
of the bacterial chromosome by transducing an auxotrophic marker in that
region to prototrophy, thereby introducing new mutations in the neighbor-
hood. This method has been used to isolate many different temperature-
sensitive mutations in genes of unknown function in particular regions of
the chromosome. Since the method is very simple, it can be used to
saturate any region of the map with mutations in essential genes, or for
various types of genetic manipulations. Although hydroxylamine-
mutagenized phage P22 and S. typhimurium have been used, the method
should be applicable to other mutagens and bacteria and transducing
phage.
Mutton, J. J. and C. Hackney.
Metabolism of Cigarette Smoke Condensates by Human and Rat Homogenates
to Form Mutagens Detectable by S_. typhimurium TA1538. CANCER
RES., XXV: 2461-2466, 1975. 19 refs.
Nineteen fractions of whole condensate of smoke from the University of
Kentucky Reference Cigarette IRI were tested for mutagenicity in vitro
using a bacterial indicator system.
Mutagenicity testing -- procedure of Ames.
Imray, F. P. and D. G. Macphee.
Spontaneous and Induced Mutability or Frameshift Strains of S. typhimurium
carrying UvrB and PolA Mutations. MUTAT. RES., XXXIV: 35-42,
1976. 18 refs.
Three strains of S. typhimurium carrying frameshift mutations affecting the
histidine genes showed increased, sensitivity to mutagenesis by ICR-191 if
they were made deficient in excision repair by deleting the UVRB gene.
One frameshift strain also showed increased sensitivity to mutagenesis by
ICR-191 when it carried either of two different polA alleles, whereas the
hisD3052 and hisC207 frameshifts reduced sensitivity to mutagenesis in the
presence of these alleles. Studies of spontaneous back mutation to
prototrophy revealed significant mutator effects of the polAl mutation on
reversion of the hisD3052 frameshift and of the polA3 mutation on rever-
54
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sion of the hisD3076 frameshift. Other smaller imitator effects of the
polA alleles on reversion of the his may also be present.
Mutagenicity testing -- procedure of~Ames.
Ishidate, M., Jr., K. Yoshikawa and M. Nakadate.
Studies on Screening Methods for Carcinogens in Vitro: Comparative
Studies on Chromosomal Aberration and Bacterial Mutation Induced by
N-acylated N-nitroso Compounds. MUTAT. RES., XXXVIII: 339-340,
1976.
A comparative study of N-acylated N-nitroso compounds, using the
mammalian cytogenetic assay, the rec assay with B. subtilis and the point
mutation assay in E. coli and/or S. typhimurium.
Ishizawa, M. and H. Endo.
Mutagenesis of Bacteriophage T4 by a Carcinogen, 4-nitroquinoline 1-oxide.
MUTAT. RES., XII: 1-8, 1971. 34 refs.
The mutagenic behavior of 4-nitroquinoline I-oxide was investigated in
bacteriphage T4. It was mutagenic for intracellular but not for extra-
cellular phages. Mutations induced in the rll region of T4 by treatment
of intracellular phages with the carcinogen were classified. More than
half the mutants were of the transition type revertible with the base
analogues, but nearly all failed to respond to hydroxylamine mutagenesis.
None of the induced mutants was capable of reverting with the carcinogen
or prof la vine.
Mutagenicity testing -- T4 bacteriophage.
Isono, K., and J. Yourno
Chemical Carcinogens as Frameshift Mutagens: Salmonella DNA Sequence
Sensitive to Mutagenesis by Polycyclic Carcinogens. PROC. NAT.
ACAD. SCI. USA, LXXI: 1612-1617, 1974. 23 refs.
Other investigators have shown that several polycyclic carcinogens are
frameshift mutagens in Salmonella. Mutagenic potency of these compounds
is assessed by ability to induce reversion of histidine-requiring frameshift
mutants to prototrophy.
Mutagenicity testing ~ procedure of Ames.
Kada, T.
Rec Assay with Cold Incubation With and Without Metabolic Reactivation in
Vitro. MUTAT. RES., XXXVIII: 34, 1976.
Improvement in the sensitivity by the above procedures with cold incubation
allowed us to carry out the rec assay in combination with activation with
rat liver homogenate in vitro.
Mutagenicity in B. subtilis.
55
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Kafer, E., P. Marshall and G. Cohen.
Well-Marked Strains of Aspergillus for Tests of Environmental Mutagens:
Identification of Induced Mitotic Recombination and Mutation. MUTAT.
RES., XXXVIII: 141-146,1976. 17 refs.
Induction of mitotic recombination in diploids of A. nidulans is used as an
indicator of mutagenic effects, and the induced"segregants are identified
either as mitotic crossovers or as products resulting from chromosomal
segregation. However, for 'these last systems, better strains are
available which can facilitate identification of the various types of induced
segregants and help elucidate the effects of the environmental mutagen.
Mutagenicity procedures -- Aspergillus.
Kappas, A., et al.
Benomyl -- A Novel Type of Base Analogue Mutagen? MUTAT. RES., XL:
379-382, 1976. 16 refs.
It is believed that the action of benomyl may be understood if it is seen as
a novel type of mutagen needing to be incorporated into DNA but once
incorporated, seen by the cell as a non-pairing purine with a large alkyl
or aryl group attached.
Mutagenicity testing by the procedure of / ies (Salmonella) and in E. coli.
Kee, S. }., and J. E. Haber.
Cell Cycle-Dependent Induction of Mutations Along a Yeast Chromosome.
PROG. NAT. ACAD. SCI. USA, LXII: 1179-1183, 175. 20 refs.
The relation between DNA replication and the action of the mutagen N-
methyl-N'-nitro-N-nitrosoguanidine has been studied in S. cerevisiae.
The frequencies of reversion to prototrophy of six autotrophic markers
located along one arm of chromosome VII were examined as a function of
the vegetative cell cycle. Exponentially growing cells were treated with
nitrosoguanidine and then separated by zonal rotor centrifugation into
fractions equivalent to stages in the cell cycle. The frequency of
reversion of five of the six markers is greatest during the period of DNA
replication. Each marker has a single point of maximum reversion,
approximately 10-fold greater than the frequency observed at other points
in the cell cycle. For any one marker the effect of nitrosoguanidine is
restricted to an interval shorter than the period of DNA replication. The
two markers most distant from each other, ade5 and leul, both have their
highest reversion frequency early during DNA replication. The results
indicate that nitrosoguanidine acts primarily during DNA replication and
that different markers appear to be affected at different intervals during
the DNA biosynthetic period.
Mutagenicity testing in yeasts.
56
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Kier, L. D., E. Yamasaki and B. N. Ames.
Detection of Mutagenic Activity in Cigarette Smoke Condensates. PROC.
NAT. ACAD. SCI. USA, LXXI: 4159-4163, 1974. 23 refs.
The S. typhimurium microsomal test system for mutagenic activity was used
to "detect the presence of mutagenic compounds in the smoke condensates
of several types of cigarettes. The condensates were shown to contain
compounds which could cause frameshift mutations when activated by
microsomal enzymes. Most of the activity of the whole condensate was in
basic fractions and in a weakly acidic fraction.
Mutagenicity testing -- procedure of Ames.
Kondo, S., et al.
Base-Change Mutagenesis and Prophage Induction in Strains of E. coli With
Different DNA Repair Capacities. GENETICS, LXVI: 187-217, 1970.
58 refs.
The method adopted in these experiments to probe mutagenesis was to
compare mutation frequencies with various agents in E. coli strains
possessing different radiosensitivities due to different DNA repair
capacities.
Mutagenicity testing by phage induction in E. coli.
Kramers, P. G. N.
The Mutagenicity of Saccharin. MUTAT. RES., XXXII: 81-92', 1975. 46
refs.
Seventeen different reports are available dealing with the mutagenic effects
of saccharin. Many are incomplete. Mainly tested as its sodium salt,
saccharin has been found to be weakly mutagenic in Salmonella at very
high doses, in Drosophila at moderate doses, and in mice at moderate to
high doses. The compound is a weak chromosome breaker in onion root
tips and in Chinese hamster cells. For most of these, and for other test
systems as well, a number of doubtful or negative results have also been
reported. Altogether the evidence for chromosome-breaking properties is
stronger than for the induction of point mutations.
Contradictions might be related to the occurrence of impurities.
Mutagenicity testing in Salmonella (Ames test), Drosophila and mice.
Kramers, P. G. N., A. G. A. C. Knaap and C. E. Voogd.
Lack of Mutagenicity of Chlormequat Chloride in Drosophila and in Bacteria.
MUTAT. RES., XXXI: 65-68, 1975. 11 refs.
Based on these data and on the suspicion that CCC, since it is a
quaternary ammonium compound, could have alkylating properties, it was
considered worthwhile to test the compound for mutagenicity.
Mutagenicity testing in Drosophila, Klebsiella pneumoniae and Citrobacter
f reundii.
57
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Legator, M. S., T. H. Connor and M. Stoeckel
Detection of Mutagenic Activity of Metronidazole and Niridazole in Body
Fluids of Humans and Mice. SCIENCE, CLXXXVIII: 1118-1119, 1975.
6 refs.
After humans were treated at therapeutic doses with the trichomonacide
metronidazole and the antischistosomal agent niridazole, mutagenic activity
was demonstrable in their urines when tested with the histidine auxotroph
°f Salmonella typhimurium. Both compounds were active in the host-
mediated assay in mice, and evidence of activity was found in the blood
and urine of mice treated with niridazole but not with metronidazole.
Mutagenicity testing by procedure of Ames (Salmonella).
Legator, M. S., T. Connor and M. Stoeckel
The Detection of Mutagenic Substances in the Urine and Blood of Man.
ANN. N. Y. ACAD. SCI., CCLXIX: 16-20, 1975. 10 refs.
This report describes the analysis of body fluids of individuals exposed to
selected drugs, and it is anticipated that this technique combined with
cytogenetic and repair studies will greatly extend our ability to detect
mutagenic agents in the human population.
Mutagenicity testing by procedure of Ames (Salmonella).
Legator, M. S., and H. V. Mailing.
The Host-Mediated Assay, a Practical Procedure for Evaluating Potential
Mutagenic Agents in Mammals. CHEM. MUTAGENS: PRIN. METHODS
THEIR DETECT., II: 569-589,1971. 35 refs.
1 this assay, the mammal, during treatment with a potential chemical
mutagen, is injected with an indicator microorganism in which mutation
frequencies can be measured. After a sufficient time period, the micro-
organisms are withdrawn from the animal and the induction of mutants
determined. The comparison between the mutagenic action of the
compound (a) on the microorganism directly and (b) in the host-mediated
assay indicated whether (1) the host can detoxify the compound or (2)
mutagenic products can be formed as a result of host metabolism.
Mutagenicity testing by procedure of Ames (Salmonella) and a heterokaryon
of Neurospora crassa.
Legator, M. S., M. Stoeckel and T. Connor
Techniques for Isolating Mutagenic Substances From Urine and Blood of
Treated Mammals Using Histidine Auxotrophs of S. typhimurium as the
Indicator Organisms. MUTAT. RES., XXVI: 456, 1974.
An abstract
Mutagenicity testing by procedure of Ames (Salmonella)
58
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Legator, M. S., S. Zimmering and T. H. Connor
The Use of Indirect Indicator Systems to Detect Mutagenic Activity in
Human Subjects and Experimental Animals. CHEM. MUTAGENS: PRIN.
METHODS THEIR DETECT., IV: 171-191, 1976. 22 refs.
A discussion of host-mediated assay relative to other mutagenicity screens.
Mutagenicity testing by procedure of Ames (Salmonella).
Legator, M. S., et al.
Mutagenic Effects of Captan. ANN. N. Y. ACAD. SCI., CLX: 344-351,
1969. 15 refs.
Captan has proved fungicidal against a wide variety of plant and animal
pathogens. This fungicide and its related compounds are widely used as
agricultural sprays, seed treatments and as protectants in paints,
plastics, leather, and fabrics. A low toxicity has been reported in
laboratory and farm animals. Although Captan has been in wide use for
over decade, comparatively little is known about the genetic effect of
this compound. The present study has undertaken to determine possible
mutagenic effects of Captan. The mutagenic activity was evaluated in
bacteria, in a heteroploid human embryonic lung cell line and in a cell
line derived from the kidney of the rat-kangaroo.
Mutagenicity testing in E. coli, cell line, L-132.
Longnecker, D. S., et al.
Trial of a Bacterial Screening System for Rapid Detection of Mutagens and
Carcinogens. CANCER RES., XXXIV: 1658-1663,1974. 7 refs.
A bacterial test system for detection of mutagens and carcinogens based on
a DNA polymerase-deficient mutant strain of E. coli was applied to the
study of several newly synthesized nitrosamines ana other compounds.
Mutagenicity testing in E. coli.
Loprieno, N., et al.
The Use of Yeast Systems in Environmental Mutagenesis. MUTAT. RES.,
XXIX: 237, 1975.
Two alkylating monofunctional agents were used to induce genetic effects
such as gene conversions and gene recombinations in diploid strains of S.
cerevisiae and S. pombe and gene mutation in a haploid strain of S.
pombe i
Mutagenicity testing in yeast.
McCalla, D. R., and D. Voutsinos
On The Mutagenicity of Nitrofurans. MUTAT. RES., XXVI: 3-16, 1974.
36 refs.
59
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Twenty-two nitrofurans were tested for ability to induce revertants " of E.
coli WP2 and its urvA-derivative from tryp- to tryp+. All proved to Ee
mutagenic while two furan analogues proved to be inactive. Test strains
containing exrA- or recA- genes were not induced to mutate, suggesting
that mutants arise ifPthe other strains during repair of damage to DNA
by the "error-prone" repair system.
Two mutant strains isolated from WP2 uvrA- on the basis of resistance to
nitrofurazone were not mutated by nitrofurazone or N-(4-(5-nitro-2-
furyl)-2-thiazolyl) formamide indicating that the ultimate mutagens are
likely to be a reduction product rather than the nitrofurans per se.
Several of the nitrofurans cause induction of prophage leading to mass lysis
in E. coli T44 (2)A, a strain which is known to be very sensitive to heat
and"certain chemicals.
Mutagenicity testing in E. coli.
McCalla, D. R., D. Voutsinos and P. L. Olive.
Mutagen Screening With Bacteria: Nitridazole and Nitrofurans. MUTAT.
RES., XXXI: 31-37, 1975. 21 refs.
The mutagenic activity of nitrofuran derivatives and of niridazole is easily
demonstrated by spot tests using E. coli WP2 and its uvrA derivative but
not by spot tests using the S. typhimurium strains developed by Ames.
Quantitative tests show that S. typhimurium TA1538 is weakly induced to
revert by nitridazole. However, the maximum yield of revertants is well
below that obtained with E. coli WP2 uvrA. None of the Salmonella
strains respond to the three nitrofurans tested even in quantitative tests.
Those strains contain the reductase required for metabolic activation of
the nitrofurans and treatment of a uvr+ Salmonella strain with niridazole
or with nitrofurazone causes single-strand breaks in DNA.
Mutagenicity testing by procedure of Ames (Salmonella) and in E. coli.
McCann, J.
Mutagenesis, Carcinogenesis and the Salmonella Test. CHEM. TECHNOL.,
(November): 682-687, 1976. 11 refs.
A talk presented by Dr. McCann in which she discusses the Salmonella test,
how and why it works in testing environmental chemicals and modifications
of the test itself.
Mutagenicity testing by procedure of Ames (Salmonella).
McCann, J. and B. N. Ames.
A Simple Method for Detecting Environmental Carcinogens as Mutagens.
ANN. N. Y. ACAD. SCI., CCLXXI: 5-13, 1976. 29 refs.
The development of this test system, recent improvements in the test, and
evidence indicating that the test is reliable and efficient for the detection
of carcinogens as mutagens are summarized in this brief review.
60
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McCann, J. and B. N. Ames.
Detection of Carcinogens as Mutagens in the Salmonella/Microsome Test:
Assay of 300 chemicals: Discussion. PROG. NAT. ACAD. SCI. USA,
LXXIIL: 950-954, 1976. 71 refs.
About 300 carcinogens and non-carcinogens of a wide variety of chemical
types have been tested for mutagenicity in the simple Salmonella/micro-
some test. The test uses bacteria as sensitive indicators of DNA damage,
and mammalian liver extracts for metabolic conversion of carcinogens to
their active mutagenic forms. There is a high correlation between
carcinogenicity and mutagenicity: 90% (157/175) of the carcinogens were
mutagenic in the test, including almost all of the known human
carcinogens that were tested. Carcinogens negative in the test and
apparent false positives are discussed.
There is evidence that chemical carcinogens and radiation, likely to initiate
most human cancer and genetic defects, do so by damage to DNA.
Mutagenicity testing by procedure of Ames (Salmonella).
McCann, J. and B. N. Ames.
Dscussion Paper: The Detection of Mutagenic Metabolites of Carcinogens in
Urine With the Salmonella/Microsome Test. ANN. N. Y. ACAD. SCI.,
CCLXIX: 21-25, 1975. 20 refs.
It is recommended that the Salmonella/microsome in vitro test be used for
the immediate screening of industrial chemicals, food additives, drugs and
other chemicals to which humans are exposed until more extensive animal
tests are conducted.
Mutagenicity testing by procedure of Ames (Salmonella).
McCann, J. and B. N. Ames.
The Salmonella/Microsome Mutagenicity Test: Predictive Value for Animal
Carcinogenicity. To appear in ORIGINS OF HUMAN CANCER,
Proceedings of the Conference, Cold Spring Harbor Laboratory, New
York, 1976. 62 refs.
A discussion of the Ames Mutagenicity Test (Salmonella) relative to
carcinogenicity.
McCann, J., et al.
Detection of Carcinogens as Mutagens: Bacterial Tester Strains With R
Factor Plasmids. PROC. NAT. ACAD. SCI. USA, LXXII: 979-983,
1975. 31 refs.
This paper extends the utility of the previously described method by
introducing two new bacterial strains which can detect many carcinogens
not detected before or with less sensitivity. The new strains TA100 and
TA98 contain an R factor plasmid. The R factor increases mutagenesis
with certain mutagens, but not others. Mutagens that become more
effective work through an error-prone recombinational repair.
Mutagenicity testing by the procedure of Ames.
61
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McCann, J., et al.
Detection of Carcinogens as Mutagens in the Salmonella/Microsome Test:
Assay of 300 Chemicals. PROC. NAT. ACAD. SCI. USA, LXXII:
5135-5139, 1975. 72 refs.
About 300 carcinogens and non-carcinogens of a wide variety of chemical
types have been tested for mutagenicity in the simple Salmonella/micro-
some test. The test uses bacteria as sensitive indicators for DNA
damage, and mammalian liver extracts for metabolic conversion of
carcinogens to their active mutagenic forms. Quantitative mutagenicity
data from linear dose-response curves are presented. There is a high
correlation between carcinogenicity and mutagenicity.
Mutagenicity testing by procedure of Ames (Salmonella).
McCann, T., et al.
Mutagenicity of Chloroacetaldehyde, a Possible Metabolic Product of 1,2-
dichloroethane (Ethylene Bichloride), Chloroethanol (Ethylene
Chlorohydrin), Vinyl Chloride, and Cyclophosphamide. PROC. NAT.
ACAD. SCI. USA, LXXII: 3190-3193, 1975. 60 refs.
Chloroacetaldehyde is mutagenic in the previously described bacterial test
system and is of interest because it is a possible metabolite in mammals of
the large volume industrial chemicals, 1,2-dichloroethane and vinyl
chloride and of the antineoplastic agent Cyclophosphamide. Chloro-
acetaldehyde reverts a new Salmonella bacterial tester strain TA100.
Chloroacetaldehyde is shown to be hundreds of times more- effective in
reversion of TA100 than is chloroethanol, a known metabolic precursor of
Chloroacetaldehyde and a possible metabolite of dichloroethane and vinyl
chloride, or than vinyl chloride, which is itself mutagenic for TA100.
Chloroethanol is shown to be activated by rat liver homogenates to a more
highly mutagenic form with reversion properties similar to Chloro-
acetaldehyde .
Mutagenicity testing by procedure of Ames (Salmonella).
McCuen, R. W., G. Stohrer and F. M. Sirotnak.
Mutagenicity of Derivatives of the Oncogenic Purine N-Oxides. CANCER
RES., XXIV: 378-384, 1974. 42 refs.
Acetoxy esters of purine N-oxides inactivate and induce mutations in B.
subtilis-transforming DNA. The esters were the chemical models available
for the sulfate esters believed to be formed in vivo. There is a
reasonable correlation between the mutagenicity of various acetoxy esters
and the oncogenicity of the parent N-oxide derivatives. The acetoxy
esters of 3-hydroxyxanthine and 3-hydroxy-l-methylguanine were the
most potent mutagens. The acetoxy ester of 7-hydroxyxanthine was also
a strong mutagen. Most of the 3-acetoxyxanthine-induced mutations
spontaneously reverted to wild type. It was concluded that mutation
induction in transforming DNA by the acetoxy esters of purine N-oxides
occurs by both transition and trans version base-pair substitution.
Mutagenicity testing in B. subtilis (transforming DNA).
62
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MacGregor, J. T., and L. E. Sacks.
The Speculation of B. subtilis as the Basis of a Multi-gene Mutagen
Screening Test. MUTAT. RES., XXXVIII: 271-286, 1976. 60 refs.
The sporulation system of B. subtilis provides the basis for detection of a
wide variety of mutagens.
The effectiveness of the test, relative to other test systems, remains to be
determined.
Mutagenicity testing in a sporulating system (B. subtilis).
MacPhee, D. G.
Salmonella typhimurium his G46 (R-Utrecht): Possible Use in Screening
Mutagens and Carcinogens. APPL. MICROBIOL., XXVI: 1004-1005,
1973. 3 refs.
S. typhimurium LT2 his G46 becomes a more sensitive strain for assaying
mutagens and carcinogens when it carries the resistance transfer factor
R-Utrecht.
Mutagenicity testing by procedure of Ames (Salmonella).
Maher, V. M., et al.
Mutations and Decreases in Density of Transforming DNA Produced by
Derivatives of the Carcinogens 2-acetyl-aminogluorene and N-methyl-4-
aminoazobenzene. MOL. PHARMACOL., IV: 411-426, 1968. 50 refs.
The observations in this paper, while suggestive of a role for mutation in
carcinogenesis by AAF and MAB, also emphasize the problems inherent in
the interpretation of such data on the mutagenic activity of chemical
carcinogens. Reactive compounds, such as the alkylating agents and the
esters studied above, react not only with DNA, but also with RNA,
protein and probably other constitutents. Hence, the ability of a
carcinogen to induce mutations, even in a system that avoids. metabolism
of the agent, cannot provide proof that a mutational mechanism is
involved in the carcinogenic process it induces. Nevertheless, assays for
mutagenesis in nonmetabolizing systems appear to be useful tools in
searches for the ultimate biologically reactive forms of chemical
carcinogens.
Mutagenicity testing in B. subtilis (transforming DNA).
Malaveille, C., et al.
Comparative Mutagenicity Studies With S. typhimurium of Dimethylnitrosa-
mine (DMN) and Diethylnitrosamine (DEN), After Metabolic Activation
With Liver and Lung Microsomes. MUTAT. RES., XXXIX: 238, 1975.
An abstract on mutagenicity
Mutagenicity testing by procedure of Ames (Salmonella).
63
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Mailing, H. V.
Dimethylnitrosamine: Formation of Mutagenic Compounds by Interaction With
Mouse Liver Microsomes. MUTAT., RES., XIII: 425-429, 1971. 20
refs.
Dimethylnitrosamine (DMN) is a potent carcinogen in several rodents. The
carcinogenicity of the compound appears to be organ- and species-specific
and depends on the route of administration.
Mutagenicity testing by procedure of Ames (Salmonella).
Meadows, M. G., S.-K. Quah and R. C. von Borstel.
Mutagenic Action of Hycanthone and IA-4 on Yeast. J. PHARMACOL. EXP.
THER., CLXXXVII: 444-450, 1972. 22 refs.
Two antischistosomal compounds, hycanthone and IA-4, were tested for
their mutagenicity in the yeast S. cerevisiae. The test system included
measurement of survival of the yeast and reversion of the mutants hisl-7
hom3-10 and lysl-1. Reversion of the mutant- hisl-7 indicates that
mutagenicity isriy base substitution, reversion of hom3-10 suggests that
mutagenicity is by base additions or deletions, and reversion of lysl-1
may be by forward mutation to supersuppression (probably due to Dase
substitution, base addition or base deletion) or by reversion of the super-
suppressible locus itself (believed to be by base substitution).
Hycanthone at pH 5.9 and 7.0 depresses survival and reverts all three
markers in our test system. IA-4 at pH 5.9 is not mutagenic in our
experiments, although it does depress survival slightly.
Mutagenicity testing in yeasts.
Milvy, P., and A. J. Garro.
Mutagenic Activity of Styrene Oxide (1,2-epoxyethly-benzene), a Presumed
Styrene Metabolite. MUTAT. RES., XL: 15-18, 1976. 12 refs.
Styrene, in contrast to vinyl chloride which is mutagenic per se for S.
typhimurium, did not exhibit mutagenic activity. Inhaled styrene vapor
is however rapidly metabolized. Earlier toxicological studies in man
indicated that the metabolism of styrene did not appear to be harmful and
its current threshold limit value (TLV) is 100 ppm, 8 h time weighted
average (Federal Register 39 [1974] 23543). However, considering the
correlation between mutagenic and carcinogenic activities which are now
emerging, and the established carcinogenic activity in man of the related
monomer vinyl chloride, for which a TLV of 1 ppm recently has been set,
we suggest that inhaled styrene vapor may be activated to a potentially
carcinogenic compound and that exposure at the currently acceptable
levels of styrene may pose a health threat to workers.
Mutagenicity testing by procedure of Ames (Salmonella).
64
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Mohn, G. R., and F. J. De Serres.
On The Mutagenic Activity of Some Hair Dyes. MUTAT. RES., XXXVIII:
116-117, 1976.
An abstract.
Mutagenicity testing by procedure of Ames (Salmonella) and in E. coli.
Mohn G., et al.
Mutagenicity Studies in Microorganisms in Vitro, with Extracts of Mammalian
Organs, and With the Host-Mediated-Assay. MUTAT. RES., XXIX:
221-233, 1975. 20 refs.
The paper is restricted to a few points of practical importance concerning
differential DNA repair, plate tests versus liquid tests, new developments
of the host-mediated assay, and interactions between mutagenic chemicals.
Monti-Bragadin, C., M. Tamaro and E. Banfi.
Mutagenic Activity of Platinum and Ruthenium Complexes. CHEM.-BIOL.
INTERACT., XI: 469-472, 1975. 7 refs.
cis-Dichlorodiammineplatinum(11) ( cis-PtCl2(NH3)2) and dichlorotetrakis
(dimethylsulfoxide) ruthenium(ll) TRuCl2 (DMSO)4) have been tested as
mutagens for strains of S. typhimurium carrying the his G46 missense
mutation. Their activity, which has been compared with the activity of
mitomycin C, depends on the presence in the test bacteria of the pKMlOl
plasmid and is affected by the function of the excision repair system. It
seems that each drug interacts with DNA by a different mechanism.
Mutagenicity testing by procedure of Ames (Salmonella).
Murayama, I.
Mutation by Mitomycins in the Ultraviolet Light-Sensitive Mutant of E. coli.
MUTAT. RES., XVIII: 117-119, 1973. 16 refs.
This paper presents evidence that monofunctional mitomycins induced
mutation in UV-sensitive strains with much higher frequency than that in
wild-type bacteria, while MRC did not induce mutation in these Uvr-
strains.
Mutagenicity testing in E. coli.
Nakajima, T., and S. Iwahara.
Mutagenicity of Dimethylnitrosamine in the Metabolic Process by Rat Liver
Microsomes. MUTAT. RES., XVIII: 121-127, 1973. 10 refs.
The mutagenicity of dimethylnitrosamine for bacteria was investigated by
means of the metabolic activation process of the compound with rat liver
microsomes.
Three strains of streptomycin (SM)-dependent E. coli having tetracycline
(TC)-resistance factor (Sd- E. coli (TC) were derived for this study.
65
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The reverse mutation in these strains from SM dependence to non-
dependence was used as the marker for mutagenicity. The drug
resistance factor (R factor) which was transferred to these strains was
used in order to get around the bacterial contamination throughout the
experiments. The study of the mutagenicity of DMN metabolites has been
made by incubating DMN with rat liver microsomes and cofactor system in
the presence of indicator bacterial cells.
The reverse mutation was markedly induced for all of three strains in the
complete incubation mixture but it was not observed when the cofactor
system was ommitted or the liver microsomal suspension was replaced by
the kidney cell sap. When the indicator bacterial cells were added to the
mixture in which DMN was previously incubated with the microsomes and
cofactor system, the mutagenicity was extremely decreased.
Mutagenicity testing in E. coli.
Neale, S.
Mutagenicity of Nitrosamides and Nitrosamidines "in Microorganisms and
Plants. MUTAT. RES., XXXII: 229-266, 1976. 232 refs.
Nitrosamides, nitrosamidines and nitrosamines, which comprise one of the
most potent groups of carcinogens known, are also highly matagenic.
Non-mammalian systems, with the exception of Drosophila, generally lack
the metabolic activity required to convert compounds such as the
nitrosamines to active mutagens or carcinogens; the mutagenic action of
those nitroso compounds which require metabolic activation has been
reviewed separately in this series by Montesano and Bartsch who
discussed in detail the role of nitroso compounds in carcinogenesis.
Nitrosamides and nitrosamidines elicit exceptionally high mutagenic
responses in non-mammalian systems.
Nelson, W. H., et al.
Thermal Effects on Genetic Events in Microbial Tester Strains. SCIENCE,
LXXXIII: s54, 1976.
It is apparent that these microbial tester strains are ideal to distinguish
between heat versus microwave induced biological change.
An abstract.
Mutagenicity testing in E. coli and S. typhimurium.
Nishioka, H.
Mutagenic Activities of Metal Compounds in Bacteria. MUTAT. RES., XXXI:
185-189, 1975. 11 refs.
Fifty-Six metal compounds were tested by the rec assay. Compounds
showing positive results in the assay such as potassium dichromate,
ammonium molybdate and sodium arsenite were then examined as to their
capacities to induce reversions in E. coli Trp- strains possessing
different DNA repair pathways.
Mutagenicity testing in E. coli and B. subtilis.
66
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Oesch, F.
Differential Control of Rat Microsomal "Aryl Hydrocarbon" Monooxygenase
and Epoxide Hydratase. J. BIOL. CHEM., CCLI: 79-87, 1976. 70
refs.
In this paper is reported the following:
1. There are striking similarities in the postnatal control of epoxide
hydratase and monooxygenase in rats with respect to both endogenous
and exogenous factors. This could be taken to indicate that the two
microsomal systems, epoxide hydratase and a rate-limiting entity of the
multicomponent monooxygenase, are under common biosynthetic control,
and a selective induction might be intrinsically impossible.
2. Dissociation of epoxide hydratase and monooxygenase induction was
achieved by transplacental treatment of fetal rat liver with some, but not
all, inducers.
3. Biological relevance of selective induction was assessed by monitoring
the ability of corresponding liver preparations to lead to altered accumu-
lation of benzo[a]pyrene metabolites mutagenic for S. typhimurium
TA1537.
Mutagenicity testing by procedure of Ames (Salmonella).
Parry, J. M.
Mitotic Recombination in Yeast as a Test of Genetic Damage. LAB.
PHACT., XXI: 417-419, 1972. 16 refs.
In the presence of mutagenic agents, heteroallelic diploid cultures of the
yeast Saccharomyces cerevisiae produce prototrophic recombinants by a
process of mitotic gene conversion. This process is characterized by a
lack of specificity with regard to the mode of action of the mutagen.
Thus mitotic gene conversion provides a convenient technique for the
detection of possible mutagenic activity, using a eukaryotic organism. A
simple technique suitable for the detection of the genetic activity of
environmental chemicals is described.
Mutagenicity testing in yeast.
Parry, J. M., D. J. Tweats and M. A. J. Al-Mossawi.
Monitoring the Marine Environment for Mutagens. NATURE, CCCLXIV:
538-540, 1976. 17 refs.
Our assay detects mutagens in the tissue of the mussel Mytilus edulis in
areas of obvious industrial pollution.
Mutagenicity testing by procedure of Ames (Salmonella) and in E. coli.
Payne, J. F.
Oil Spills: Effects of Petroleum on Marine Organisms. SCIENCE, CXCVI:
10, 1977.
Mutagenicity testing by procedure of Ames (Salmonella).
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Prival, M. J. et al.
Tris (2,3-Dibromopropyl) Phosphate: Mutagenicity of a Widely Used Flame
Retardant. SCIENCE, CXCV: 76-78, 1977. 15 refs.
Tris (2,3-dibromopropyl) phosphate, a widely used flame-retardant additive
for textiles, is mutagenic to histidine-requiring strains of £5.
typhimurium. Extracts of fabrics treated with this compound are also
capable of inducing mutations in these bacterial strains.
Mutagenicity testing by procedure of Ames (Salmonella).
Rannug, U., R. Gothe and C. A. Wachtmeister.
The Mutagenicity of Chloroethylene Oxide, Chloroacetaldehyde, 2-chloro-
ethanol and Chloroacetic Acid, Conceivable Metabolites of Vinyl
Chloride. CHEM.-BIOL. INTERACT., XII: 251-263, 1976. 28 refs.
The ability of four conceivable metabolites to cause base-pair substitution
directly in S. typhimurium TA1535 has been compared. The main
comparison was performed at initial concentrations from 0.1 to 1.5 mm.
In this region, however, a mutagenic effect was observed only with
chloroethylene oxide and Chloroacetaldehyde, the former being approxi-
mately 20 times more effective than the aldehyde when compared on a
molar basis. 2-chloroethanol and chloroacetic acid were studied also at
higher concentration, and a weak mutagenic response was found with 1M
2-chloroethanol solution. With chloroacetic acid no enhancement of the
mutation frequency could be detected.
Chloroethylene oxide was found to be approximately 450 times more effective
as a mutagen than Chloroacetaldehyde when the comparison is based on
exposure doses. Similarly, chloroethylene oxide was 10,000-15,000 times
more effective as a mutagen than ethylene oxide, used as a positive
control.
Mutagenicity testing by procedure of Ames (Salmonella).
Rannug, U., and C. Ramel.
The Mutagenicity of Waste Products from the Vinyl Chloride Industries.
MUTAT. RES., XXXVIII: 113, 1976.
An abstract.
Mutagenicity testing by procedure of Ames (Salmonella).
Rao, T. K., et al.
Correlation of Mutagenic Activity of Energy Related Effluents With Organic
Constituents. EIGHTH ANNUAL MEETING ENVIRON. MUTAGEN SOC.
Colorado Springs, Colorado, 1977, pp. 47-48.
An abstract.
We have applied the short-term testing to crude products and effluents from
the synthetic fuel technologies. Class fractionation and column chromato-
graphy of the test materials and the coupled bioassays can be used to
identify the most active fractions.
Mutagenicity testing by procedure of Ames (Salmonella).
68
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Rasmussen, R. E., and I. Y. Wang.
Dependence of Specific Metabolism of Benzo[a]pyrene on the Inducer of
Hydroxylase Activity. CANCER RES., XXXIV: 2290-2295, 1974. 24
refs.
The data presented here indicate that PB and polycyclic hydrocarbons
induced mixed-function oxidases in rat liver which had different
specificities toward BP. The observed differences in the mutagenic
activity of BP when metabolized by PB- or 3-MC-induced enzymes were in
part due to differences in the induced level of epoxide hydrase. It
cannot be ruled out that other metabolites of BP may also be responsible
for some of its mutagenic and carcinogenic effects, but our results
strongly favor the long-held idea that the K region is probably involved.
Mutagenicity testing by procedure of Ames (Salmonella).
Rosenkranz, H. S., Jr., W. T. Speck and J. E. Stambaugh.
Mutagenicity of Metronidazole: Structure-Activity Relationships. MUTAT.
RES., XXXVIII: 203-206,1976. 14 refs.
Recent reports of the mutagenicity of metronidazole for bacterial species
have caused concern regarding the safety of this widely used antipro-
tozoan and antibacterial agent. Because it might be possible to
synthesize derivatives of metronidazole devoid of genetic activity yet still
retaining chemotherapeutic effectiveness, it was thought of interest to
examine the mutagenic activity of several simple derivatives of
metronidazole.
Mutagenicity testing by procedure of Ames (Salmonella).
Rubin, I. B., et al.
Fractionation of Synthetic Crude Oils from Coal for Biological Testing.
ENVIRON. RES., XII: 358-365, 1976. 18 refs.
A separation procedure that has been used extensively for the reproducible
fractionation of cigarette smoke condensate for carcinogenic properties has
been applied to coal liquefaction products. Two types of product oils,
one a light oil and the other a heavy tar, have been processed success-
fully by this procedure. Mutagenicity of the major fractions of the light
oil product was tested by microbiological techniques using several strains
of £5. typhimurium, and some mutagenic effect was shown by four of the
fractions! The possible carcinogenicity and mutagenicity of the individual
fractions are discussed in relation to the reported effects of corresponding
cigarette smoke condensate fractions.
Mutagenicity testing by procedure of Ames (Salmonella).
Ryttman, H., and G. Zetterberg.
Induction of Mitotic Recombination With N-methyl-N'-nitro-N-nitrosoguanidine
(MNNG) in Saccharomyces cerevisiae. A Comparison Between Treat-
ment in Vitro and in the Host-Mediated Assay. MUTAT. RES.,
XXXIV: 201-216, 1976. 29 refs.
69
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Two methods, treatment in vitro and the host-mediated assay method, were
compared in their ability to demonstrate the induction by MNNG of mitotic
recombination in a diploid strain of S. cereyisiae. MNNG had a strong
activity in vitro but not in the host-mediated assay at the concentrations
tested. When the genetic effects of MNNG have been tested in different
test systems, sometimes negative, sometimes positive results have been
obtained. The relevance of different tests for risk evaluation is
discussed, and it is concluded from the data on MNNG that tests on whole
mammals may sometimes give false negative results because the cells tested
are in parts of the body less accessible to the mutagen. Increasing doses
of MNNG by treatment in vitro gave decreasing frequencies of mitotic
recombination, indicating damage to the recombinational system in the
cells. Dose-response relationships for recombination and mutation are
discussed.
Mutagenicity testing in S. cerevisiae.
Seller, J. P.
Toxicology and Genetic Effects of Benzimidazole Compounds. MUTAT.
RES., XXXII: 151-168,1975. 90 refs.
Benzimidazoles have been tested for mutagenicity in a variety of test
systems. The first investigations were made with microorganisms and
only lately have mammals been used to assess mutagenic activity for these
compounds. The mutation of E. coli to streptomycin resistance has been
used to reveal the weak mutagenic properties of benzimidazole. With the
S. typhimurium strains of Ames, it was found that benzimidazole acts as a
b~ase-substituting agent.
A discussion of the toxicity of benzimidazole compounds.
Shahin, M. M.
The Non-Mutagenicity and -recombinogenicity of Vinyl Chloride in the
Absence of Metabolic Activation. MUTAT. RES., XL: 269-272, 1976.
7 refs.
In view of the fact that most carcinogens are also mutagens, it appears
desirable to determine whether or not the carcinogen vinyl chloride is
capable of interfering with the genetic material. We have tested the
ability of this compound to induce reversion and mitotic recombination in
the yeast S. cerevisiae.
Mutagenicity testing in Saccharomyces cerevisiae.
Shahin, M. M., and R. C. von Borstel.
Genetic Activity of the Antimicrobial Food Additives Af-2 and H-193 in
Saccharomyces cerevisiae. MUTAT. RES., XXXVIII: 215-224, 1976.
27 refs.
The genetic activity of the antimicrobial food additives AF-2 and H-193 has
been investigated in S. cerevisiae. The strains chosen for the studies
were D5 for the induction of mitotic recombinational events and XV185-14C
70
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for the induction of reversion of the mutants. When three concentrations
of AF-2 were used in the reversion system of strain XV185-14C, there
was an increase in the frequency of hom+ and his-i- revertants as a
function of incubation time, while the lysine mutant exhibited a very low
frequency of induced reversion. When AF-2 and H-193 were compared at
the same concentration and exposure time, AF-2 exhibited a higher
genetic activity in both systems than H-193. However, H-193 was
genetically more active in inducing revertants than AF-2, when the
comparison was made at the -same survival level. Cells of both haploid
and diploid strains were found to be more sensitive to inactivation by
AF-2 than by H-193. The haploid strain was more sensitive to both
compounds than the diploid strain.
Mutagenicity testing in S. cere visiae.
Shahin, M. M., and R. C. von Borstel
Mutagenic and Lethal Effects of a-Benzene Hexachloride, Dibutyl Phthalate
and Trichloroethylene in Saccharomyces cere visiae. To be published in
MUTAT. RES.
§• cerevisiae strain XV185-14C for reversion studies was used to investigate
the genetic activity of a-benzene hexachloride dibutyl phthalate and
trichloroethylene. The results indicate that none of the three compounds
was genetically active when yeast cells were treated in phosphate buffer
(pH 7.0) in the absence of metabolic conversion. However, in the
presence of the 9000 g supernatant of mice liver homogenate, NADP,
glucose-6-phosphate, phosphate buffer (pH7.4), MgCl2 KC1, the
components which were used for the metabolic conversion, trichloroethy-
lene proved to be a powerful mutagen. It increases the frequency of
homoserine, histidine and lysine revertants over those of the control
levels. Trichloroethylene appears to induce frameshift as well as base
substitution mutations.
Mutagenicity testing in yeasts.
Sharma, C. B. S. R., and R. K. Sahu.
Cytogenetic Hazards from Agricultural Chemicals. I. A Preliminary Study
on the Responses of Root Meristems to Exotoxin from B. thuringiensis
a Constituent of a Microbial Insecticide, Thuricide. MUTAT. RES.,
XLVI: 19-26, 1977. 46 refs.
It is reported for the first time that the exotoxin, thuringiensin A, from
Bacillus thuringiensis, a component of the insecticide thuricide, inhibits
spindle and cytokinesis and induces micronuclei, chromocentric nuclei and
minor deviations in spindle biprophases and bimetaphases. Spindle seems
to have been inhibited even in bimetaphase. Microtubular systems and
chromosomes are implicated as the primary targets. Most effects resemble
those of caffeine, colchicine, aminopyrin, chloral hydrate and vinblastine
to different extents, and are therefore suggestive of the anti-neoplastic
and mutagenic potentialities of the exotoxin. The extensive use of
thuricide on crop plants in view of its mutagenic potential, may be
hazardous. The results also suggest that the exotoxin may be used as a
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pretesting agent in chromosome analysis and as a candidate-tagging tool
for synchronization and cell cycle analysis, besides its probable utility in
studies on cancer cells.
Shirasu, Y., et al.
Mutagenicity Screening of Pesticides in the Microbial System. MUTAT.
RES., XL: 19-30,1976. 24 refs.
A survey on the mutation induction capacity was made in the microbial
system on 166 pesticides, including 57 fungicides, 63 herbicides and 46
insecticides. The screening methods consisted of the rec-assay
procedure, a sensitivity test utilizing H17 Rec+ and M45 Rec- strains of
§.• subtilis, as well as the reversion assays on plates utilizing auxotrophic
strains of E. coli (WP2) and S. typhimurium. Chemicals inducing
reversions were detected only among those showing positive effects in the
rec-assay but not among negative samples. In addition to Captafol,
Captan, Dexon and NBT of which mutagenicities have been previously
reported, Dichlorvos, Flopet, 2-hydrazinoethanol (HEH), 5-nitro-l-
naphthanitrile (NNN) and Vamidothion were found to be mutagens in our
systems.
Mutagenicity testing by procedure of Ames -- Salmonella, B. subtilis and in
E. coli.
Siebert, D.
A New Method for Testing Genetically Active Metabolites. Urinary Assay
With Cyclophosphamide (Endoxan, Cytoxan) and Saccharomyces
cerevisiae. MUTAT. RES., XVII: 307-314, 1973.
Cylcophosphamide (Endoxan, Cytoxan), a cytostatic substance, was tested
for its genetic activity in S. cerevisiae. The test system used was
induction of (1) back mutation and (2) mitotic gene conversion. Given
directly to yeast, cyclophosphamide showed no genetic effect. After oral
application to BD rats the urine showed medium mutational activity but
strong convertogenic activity up to a 100-fold increase of induced
convertants. In the host-mediated assay (injection of yeast into the
ventral cavity), cyclophosphamide was only weakly active.
Mutagenicity testing in S. cerevisiae.
Siebert, D., and G. Eisenbrand.
Genetic Effects of Some New Bifunctional and Water-Soluble Analogs of the
Anti-Cancer Agent l,3-Bis(2-chloroethyl)-l-nitrosourea (BCNU) in S.
cerevisiae. MUTAT. RES., XLII: 45-50, 1977. 10 refs.
A series of l-(2-chloroethyl)-l-nitrosoureas were examined for their genetic
activities. BCNU was simultaneously tested as an established, clinically
used reference compound. A diploid strain of S. cerevisiae, heteroallelic
at the gene loci ade2 and trp5 was used as a test system for the
induction of mitotic gene conversion (intragenic recombination).
Mutagenicity testing in S. cerevisiae.
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Siebert, D., F. K. Zimmermann and E. Lemperle.
Genetic Effects of Fungicides. MUTAT. RES., X: 533-543, 1970. 39 refs.
Fourteen fungicides have been tested for genetic activity on diploid cells of
the ascomycete S. cerevisiae. The test system used was induction of:
(1) mitotic gene conversion at 2 different loci; and (2) cytoplasmic
respiratory-deficient mutants. Two fungicides turned out to be strongly
active in inducing mitotic gene conversion when applied as commercial
preparations; Orthophaltan and Polyram-combi and poly-ethylenebis.
Cignolin, used in dermatology, did not induce mitotic gene conversion but
induced bytoplasmic respiratory-deficient mutation at frequencies close to
100%. With four more fungicides, only a weak apparent induction of gene
conversion could be observed: Antracol, Basfungi and polypropylenebis,
Dithane-Ultra and Captan.
Mutagenicity testing in S. cerevisiae.
Simmon, V. F., and R. G. Tardiff.
Mutagenic Activity of Drinking Water Concentrates. Source unknown.
An abstract concerned with drinking water concentrates.
Mutagenicity testing by procedure of Ames (Salmonella).
Skopek, T. R., et al.
A Quantitative Forward Mutation Assay in Salmonella typhimurium Using
8-azaguanine Resistance as a Genetic Marker. PROC. NAT. ACAD.
SCI., Preprint. 15 refs.
A quantitative forward mutation assay has. been developed using S.
typhimurium in which resistance to the purine analog 8-azaguanine (SAG)
is used as a genetic marker. Resistance to SAG results from the loss of
xanthine-guanine-phos-phoribosyl transf erase (XGPRT), an enzyme
responsible for the transport and phosphoribosylation of xanthine,
guanine, and 8 AG. Here we present the assay protocol, the concentra-
tion dependent toxicity and mutagenicity of four known mutagens. p-
propio=lactone (pPL) and reconstruction experiments tested the assay or
possible bias. The relative merits of forward versus reverse mutation
assays are discussed.
Mutagenicity testing by procedure of Ames (Salmonella).
Speck, W. T., and H. S. Rosenkranz.
Mutagenicity of Azathioprine. CANCER RES., XXXVI: 108-109, 1976. 9
refs.
Azathioprine is mutagenic for S. typhimurium. Demonstration of this
mutagenic effect requires a period of anaerobic incubation of the bacteria
with the test agent.
Mutagenicity testing by procedure of Ames (Salmonella).
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Speck, W. T., A. B. Stein and H. S. Rosenkranz.
Mutagenicity of Metronidazole: Presence of Several Active Metabolites in
Human Urine. J. NAT'L CANCER INST., LVI: 283-291, 1976. 10
refs.
Mutagenic activity was found in the urine of 10 patients given therapeutic
dosages of metronidazole orally or per vagina. Paper chromatographic
separation revealed that mutagenicity in the urine was associated with
unmodified metronidazole and at least four of its known urinary
metabolites. Activity was also recovered in a region of the chromatogram
heretofore not assigned to a metronidazole metabolite.
Mutagenicity testing by procedure of Ames — Salmonella.
Stolz, D. R., R. D. Bendall and C. T. Miller.
Mutagenic Effect of Nialamide on Salmonella typhimurium. MUTAT. RES.,
XL: 305-308, 1977. 6 refs.
The mutagenicity of an antidepressant drug, nialamide, was studied with S.
typhimurium TA1535-8. Nialamide was mutagenic for strain TA1535 in tKe
absence of rat liver extracts.
Mutagenicity testing by procedure of Ames (Salmonella).
Straus, D. S.
Induction by Mutagens of Tandem Gene Duplications in the glyS Region of
the Escherichia coli Chromosome. GENETICS, LXXVIII: 823-830,
1974. 24 refs.
Four mutagens have been found to increase the frequency of tandem gene
duplications in the glyS region of the E. coli chromosome. This result
was obtained by quantitating the spontaneous and mutagen-induced
reversion frequency of a glycyl-tRNA synthetase (gly-S) mutant.
Following mutagenesis, as many as 0.2% of the survivors were observed to
contain duplications in the gly-S region. In addition, several classes of
stable revertants of the glyS mutant have been identified.
Mutagenicity testing in E. con.
Tanooka, H.
Development and Applications of Bacillus subtilis Test Systems for
Mutagens, Involving DNA-Repair Deficiency and Suppressible
Auxotrophic Mutations. MUTAT. RES., XLII: 19-32, 1977. 27 refs.
A mutagen-tester of B. subtilis was constructed and tested with known
carcinogens. The parental strain HA101 of Okubo and Yanagida carrying
suppressible nonsense mutations in his and met genes was transformed to
carry an excision-repair deficiency mutation. The constructed strain
TKJ5211 showed a 20-30-fold higher sensitivity for His+ reversion than
the parental strain when treated with UV and UV-mimetic chemicals but
unchanged mutation frequency with X-rays and methyl methanesulfonate.
The tester strain was used in a spot test of 30 selected chemicals and
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also for testing with liver homogenate activation. The results showed an
almost equivalent but somewhat broader detection spectrum than the S.
typhimurium TA100 system. Another test method used a pair of B.
subtilis strains differing in their DNA-repair capacity, i.e., the most
UV-sensitive mutant HU-15 and a wild-type strain, to detect repair-
dependent DNA damage produced by chemicals. Spores could be used in
either test.
Mutagenicity testing in Salmonella (Ames) and B. subtilis.
Tazima, Y., T. Kada and A. Murakami.
Mutagenicity of Nitrofuran Derivatives, Including Furylfuramide, a Food
Preservative. MUTAT. RES., XXXII: 55-80, 1975. 113 refs.
Strong mutagenic as well as carcinogenic activities were revealed for several
nitrofuran derivatives and these caused doubt about the use of furyl-
furamide as a food preservative.
Mutagenicity testing in Salmonella (Ames) and E. coli and B. subtilis.
Teranishi, K., K. Hamada and H. Wantanabe.
Quantitative Relationship Between Carcinogenicity and Mutagenicity of Poly-
aromatic Hydrocarbons in Salmonella typhimurium Mutants. MUTAT.
RES., XXXI: 97-102, 1975. 14 refs.
Mutagenic activities of various polyaromatic hydrocarbons in air pollutants,
which are different in carcinogenic activities from each other, were
examined with a set of four strains of S. typhimurium. All the
compounds tested were converted to frameshift mutagens when they were
metabolized by rat liver homogenate. There was a clear quantitative
correlation between carcinogenicity and mutagenicity of PAHs tested in
strain TA1538 using the rat liver enzyme induced with both dibenz(a,h)-
anthracene and phenobarbital. On the other hand, such a correlation was
not obvious in strain TA1537.
Mutagenicity in Salmonella, procedure of Ames.
Terrasso, M.
Analysis of Samples From Industrial Sources in Houston Ship Channel Area.
Analysis of data
Mutagenicity procedure of Ames (Salmonella).
Ueno, Y., and K. Kubota.
DNA-Attackmg Ability of Carcinogenic Mycotoxins in Recombination-Deficient
Mutant Cells of Bacillus subtilis. CANCER RES., XXXVI: 445-451,
1976. 24 refs.
Thirty mycotoxins and five chemically modified toxins were tested for DNA-
attacking ability in the rec assay using the recombination-deficient mutant
of B. subtilis M45 (rec-) and the parent strain.
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Six Penicillium toxins, five Aspergillus toxins and two Fusarium toxins were
positive. Among these 13 compounds, eight have been reported to be
carcinogenic in animals.
Correlation between the rec effect and in vivo carcinogenicity of mycotoxins
is discussed.
Mutagenicity testing in Bacillus subtilis.
Venitt, S., and C. T. Busheil.
Mutagenicity of the Food Color Brown FK and Constitutents in Salmonella
typhimurium. MUTAT. RES., XL: 309-316, 1977. 11 refs.
The food color Brown FK is a mixture of p-sulphophenylazo derivatives of
m-toluylenediamine and m-phenylenediamine and is used in the UK for
coloring kippers. Brown FK and its constituents were assayed for
mutagenicity in S. typhimurium TA1535, TA1537 and TA1538. Samples of
brown typhimurium TA1535, TA1537 and TA1538. Samples of brown FK
from three manufacturers were mutagenic in TA1538 when activated by a
rat-liver supernatant fraction.
Mutagenicity testing by procedure of Ames (Salmonella).
von Borstel, R. C., and S. Igali.
Mutagenicity Testing of Antischistosomal Thioxanthenones and Indazoles on
Yeast. J. TOXIC. ENVIRON. HEALTH, I: 281-291, 1975. 27 refs.
Two antischistosomal thioxanthenones, and four antischistomal indazoles have
been tested for mutagenicity on stationary phase cells of the yeast
Saccharomyces cerevisiae. It was shown that, although there are some
gaps m the data, Hycanthone and IA-6 are mutagenic at pH 7.0,
hycanthone is mutagenic at 5.9 and none of the other compounds is
mutagenic at either pH. An excision-repair deficient strain of yeast is no
more sensitive than other strains. It was found from time-concentraton
studies on lethality that an inverse relation held: cells exposed to a
mutagenic compound are more sensitive when time of exposure was varied
and concentration of the compound was held constant, and cells exposed
to a nonmutagenic compound are more sensitive when concentration is
varied and time of exposure held constant. When the compounds were
tested on growing cells of yeast in rich media, none of the compounds is
mutagenic, although some are lethal. The kinetic behavior in reversion of
yeast exposed to these compounds shows marked departures from similar
reversion studies where yeast is exposed to radiation, implicating
different physiological mechanisms for the alteration or responses of yeast
cells exposed to the different mutagens.
Mutagenicity testing in yeasts.
Voogd, C. E.
The Mutagenic Action of some Nitrothiazoles and Nitroghiophenes. MUTAT.
RES., XXXVIII: 117, 1976.
An abstract
Mutagenicity testing in Klebsiella pneumoniae.
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Wang, C. Y., K. Murasoka and G. T. Bryan.
Mutagenicity of Nitrofurans, Nitrothiophenes, Nitropyrroles, Nitroimidazole,
Aminothiophenes, and Aminothiazoles in Salmonella typhlmurium.
CANCER RES., XXXV: 3611-3617, 1975. 30 refs.
Thirty-two heterocyclic compounds, including 24 nitroheterocycles, and
seven aminoheterocycles and derivatives and one thiophene lacking in a
nitro group were tested for mutagenic activity in S. typhimurium TA98
and TA100. All the nitroheterocycles, including nitrofurans, nitrothio-
phenes, nitropyrroles and one nitroimidazole, were mutagenic in TA100.
Thirteen were also mutagenic in TA98, 5-Nitro-2-furoic acid, a noncar-
cinogen, was mutagenic in TA100. Seven carcinogenic nitroheterocycles,
aminothiophenes and aminothiazole derivatives, and one thiophene without
a nitro group were not mutagenic. Both TA98 and TA100 were uvrB and
lacked the ability of excision repair of DNA. Among the 24 mutagenic
nitroheterocycles, only 13 compounds exhibited bacterial killing effects,
suggesting that more than one mechanism may be involved in the inter-
action of nitroheterocycles with bacterial DNA.
Mutagenicity testing by procedure of Ames (Salmonella).
Weekes, U., and D. Brusick.
In Vitro Metabolic Activation of Chemical Mutagens. II. The Relationships
Among Mutagen Formation, Metabolism and Carcinogenicity for Dimethyl-
nitrosamine and Diethylnitrosamine in the Livers, Kidneys and Lungs
of balb/cj, C57BL/6J and RF/J Mice. MUTAT. RES., XXXI: 175-183,
1975. 23 refs.
The metabolic activation of dimethylnitrosamine and diethylmtrosamine to
mutagenic intermediates was studied using an in vitro genetic assay which
measured the relative concentration and rate of formation of the active
intermediates. Microsomal preparations from the livers, lungs and
kidneys of male mice were compared for their ability to activate the two
carcinogens to mutagens. It was demonstrated that quantitative
differences in activation could be detected between organs of the three
strains and that different organs have characteristic activation kinetics.
Activation kinetics for microsomal metabolism of DMNA by liver, lung and
kidney tissues of male and female mice were also compared.
Mutagenicity testing by procedure of Ames (Salmonella).
Wheeler, L. A.. et al.
Association of Salmonella Mutants With Germfree Rats: Site Specific Model
to Detect Carcinogens as Mutagens. PROC. NAT. ACAD. SCI. USA,
LXXII: 4607-4611, 1975. 23 refs.
An association of the histidine auxotroph of S. typhimurium (strain TA1538)
within the gastrointestinal tract of otherwise germfree Sprague-Dawley
rats is maintained during periods of observation lasting as long as 7
months.
Mutagenicity testing by procedure of Ames (Salmonella).
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Wislocki, P. G., et al.
Mutagenicity and Cytotoxicity of Benzo[a]pyrene Arene Oxides, Phenols,
Quinones, and Dihydrodiols in Bacterial and Mammalian Cells. CANCER
RES., XXXVI: 3350-3357,1976. 43 refs.
Twenty-nine benzo[a]pyrene derivatives were tested for mutagenic activity
without metabolic activation in S^. typhimurium strains TA98, TA100 and
TA1538 and in Chinese hamster V79 cells.
Mutagenicity testing by procedure of Ames (Salmonella) and in mammalian
cells.
Wlodkowski, T. J., and H. S. Rosenkranz.
Mutagenicity of Sodium Hypochlorite for Salmonella typhimurium. MUTAT.
RES., XXXI: 39-42,1975. 14 refs.
Sodium hypochlorite, a standard household item, induces base-substitution
mutations in S. typhimurium. Because of its potent bactericidal effect the
mutagenicity of hypochlorite could best be demonstrated by short-term
exposure to this chemical followed by the addition of ascorbic acid to
decompose the hypochlorite.
Mutagenicity testing by procedure of Ames (Salmonella).
Wong, J. J., and D. P. H. Hsieh.
Mutagenicity of Aflatoxins Related to Their Metabolism and Carcinogenic
Potential. PROC. NATL. ACAD. SCI. USA, LXXIII: 2241-2244, 1976.
41 refs.
Aflatoxins and their animal biotransformatioh products were screened for
carcinogenic potential by using the Ames1 in vitro detection system for
carcinogens as bacterial mutagens. Aflatoxicol, aflatoxins Ql, B2 and PI,
G2, B2a and G2a were all less active than aflatoxin Bl. No compound
possesses activity in the absence of the rat liver preparation. The
relative mutagenic potency observed with this in vitro system qualitatively
correlates with in vivo carcinogenic data.
Mutagenicity testing by procedure of Ames (Salmonella).
Wood, A. W., et al.
Mutagenic and Cytotoxic Activity of Benzo[a]pyrene 4,5-,7,8-, and 9,10-
oxides and the Six Corresponding Phenols. PROC. NAT. ACAD. SCI.
USA, LXXII: 3176-3180, 1975. 30 refs.
The benzo[a]pyrene 4,5-, 7,8-, and 9,10-oxides and the six corresponding
phenols have been tested for mutagenic and cytotoxic activity in bacteria
and in a mammalian cell-culture system.
Mutagenicity testing by the procedure of Ames (Salmonella) and in
mammalian cells.
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Wood, A. W., et al.
Mutagenicity and Cytotoxicity of Benzo[a]pyrene Benzo-Rmg Epoxides.
CANCER RES., XXXVI: 3358-3366, 1976. 34 refs.
Four benzo-ring epoxides of the environmental carcinogen benzo[a]pyrene
(BP) were tested for mutagenic and cytotoxic activity in three strains of
£5. typhimurium and in Chinese hamster V79 cells.
Mutagenicity testing by the procedure of Ames (Salmonella) and in Chinese
hamster cells.
Yahagi, T., et al.
Mutagenicities of Nitrofuran Derivatives on a Bacterial Tester Strain With an
R Factor Plasmid. MUTAT. RES., XL: 9-14, 1976. 12 refs.
Many nitrofuran derivatives are known to be mutagenic on E. coli WP2 but
not on S. typhimurium TA1535, TA1536, TA1537 or TA1538. Ames and
coworkers recently obtained a new tester strain of S. typhimurium,
TA100, by putting an R factor plasmid, pKM 101, into TA1535. It was
found that all the mutagenic nitrofuran derivatives previously found to be
mutagenic on E. coli WP2 were mutagenic on this new strain TA100.
Mutagenicity testing by procedure of Ames (Salmonella and E. coli).
Yahagi, T., et al.
Mutagenicity of Carcinogenic Azo Dyes and Their Derivatives. CANCER
LETTERS, I: 91-96, 1975. 18 refs.
The mutagenicity of N,N-dimethyl-4-aminoazobenzene and N-methyl-4-amino-
azobenzene and their derivatives was shown on S. typhimurium TA100 and
TA98. S-9 Mix, obtained from rat liver after injection of polychlorinated
biphenyl, was obligatory for their mutagenic action. N-Acetoxy-N-methyl-
4-aminoazobenzene and N-benzo-yloxy-N-methyl-4-aminoazobenzene and
their 4'-methoxycarbonyl derivatives were also mutagenic on TA100 and
TA98 and did not require metabolic activation by S-9 Mix. It is
suggested that the carcinogenic effects of azo dyes may involve modifica-
tion of DNA.
Mutagenicity testing by procedure of Ames (Salmonella).
Yahagi, T., et al.
Relationship Between the Carcinogenic and Mutagenic or DNA-Modifying
Effects of Nitrofuran Derivatives, Including 2-(2-furyl)-3-(5-nitro-2-
furyl) Acrylamide, a Food Additive. CANCER RES., XXXIV: 2266-
2273, 1974. 42 refs.
The mutagenic and DNA-modifying effects of 27 nitrofuran derivatives were
studied by means of several rapid microbial assay methods. The muta-
genic effects were tested with the use of E. coli, B/r WP2 try- and WP2
try-, her-; and with S. typhimurium. TA1535, TA1536, TA1537, and
TA1538.
Mutagenicity testing by procedure of Ames (Salmonella and in E. coli).
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Yielding, L. W., W. E. White, Jr., and K. L. Yielding.
Production of Frameshift Mutations in Salmonella by a Light Sensitive Azide
Analog of Ethidium. MUTAT. RES., XXXIV: 351-358, 1976. 12 refs.
Frameshift mutations have been produced in specific repair-negative
Salmonella tester strains by photoaffinity labeling technique using
ethidium azide. Reversions requiring a +1 addition or a -2 deletion were
especially sensitive. Mutagenesis was reduced by the simultaneous
addition of non-mutagenic ethidium bromide, and was prevented by
photolysis of the azide prior to culture addition. Identical tester strains
active in DNA excision repair were not mutagenized by the azide.
Mutagenicity testing by procedure of Ames (Salmonella).
Zetterberg, G., et al..
The Influence of pH on the Effects of 2,4-D (2,4-dichlorophenoxyacetic
acid, Na SALT) on Saccharomyces cerevisiae and Salmonella
typhimurium. MUTAT. RES., XLII: 3-18, 1977. 17 refs.
The genetic effects of 2,4-D have been investigated in cells of the yeast S.
cereyisiae and of the bacterium S. typhimurium in experiments in vitro
and in vivo. Experiments in vitro showed that the killing of both yeast
and bacteria is dependent on the pH in the treatment solution of 2,4-D.
A dose-dependent increase of the frequency of mitotic gene conversion
and mitotic recombination in yeast was observed at pH 4.5 and 4.3. In
experiments in vitro with two strains of Salmonella no significant increase
of the number of revertants to prototrophy was obtained. The positive
correlation between survival of cells and dissociation of 2,4-D in the pH
region 2.8-5.0 indicates that the cells are unable to take up dissociated
2,4-D. Therefore the survival is high at a high pH when most 2,4-D is
in dissociated form, and the survival is low at a relatively low pH when
more of the 2,4-D is in its undissociated form. No genetic effects were
induced by oral administration of tolerable doses of 2,4-D in host-
mediated assays using mice as hosts and yeast or Salmonella as indicator
cells.
Mutagenicity testing in Salmonella (Ames) and S. cerevisiae.
Zimmer, D. M., and B. K. Bhuyan
Mutagenicity of Streptozotocin and Several Other Nitrosourea Compounds in
Salmonella typhimurium. MUTAT. RES., XL: 281-288, 1976. 18 refs.
The following nitrosourea compounds were compared for their ability to
induce mutation in the histidine-requiring auxotroph S. typhimurium
hisG45: MNU, Streptozotocin and its analogs SZA1 and" SZA2 and the
antitumor drugs BCNU, CCNU and DCNU. At equitpxic doses SZ, SZA1,
SZA2 and MNU were almost equally mutagenic causing 150, 42, 140 and
170 mutants/106 survivors at 20% lethal dose, although on a weight basis,
SZ was the most mutagenic of the compounds tested. Our results show
that these nitrosoureas, in common with many other drugs used in
cancer chemotherapy, are highly mutagenic.
Mutagenicity testing by procedure of Ames (Salmonella).
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Zimmermann, F K.
Induction of Mitotic Gene Conversion by Mutagens. MUTAT. RES., XI:
327-337, 1971. 55 refs.
Mitotic gene conversion generates wild-type alleles from a pair of differently
inactive alleles combined in a heteroallelic diploid. If the inactivity of
those alleles causes a nutritional requirement, production of wild-type
recombinants by mitotic gene conversion can be followed, in the yeast S.
cerevisiae, by simply plating cells on selective media. Mitotic gene
conversion can be induced by a large variety of mutagens: ionizing
radiation, UV irradiation, methylating, ethylating, propylating and
butylating agents, as well as by other alkylating agents such as
ethyleneimines, nitrogen mustards, lactones, epoxides, sultones, metabolic
derivatives of carcinogenic, aromatic amines, deaminating nitrous acid,
radical-producing hydroxyurea and the acridine mustard 2-methoxy-6-
chloro-9-(2-chloroethylaminopropylamino) acridine.
Mutagenicity in yeasts.
OTHER ASSAY SYSTEMS FOR ENVIRONMENTAL CARCINOGENS AND/OR
MUTAGENS
Arenaz, P., and B. K. Vig.
Induction of Somatic Mosaicism in the Soybean by Some Carcinogens.
GENETICS, LXXXIII: s3, 1976.
An abstract.
Carcinogenicity testing in plants.
Arlett, C. F.
Mutation Testing With Cultured Mammalian Cells. LAB. PRACT., XXI:
420-423, 1972. 15 refs.
Cultured mammalian cells can provide material for mutagenicity testing which
is relevant to man. The 8-azaguanine resistance system in Chinese
hamster cells which has been studied in detail is especially convenient for
laboratory study because mutations may be scored on the basis of simple
colony counts. A description of the system and its potential for use in
routine mutagenicity testing is provided.
Arlett, C. F.. et al.
A Comparison of the 8-azaguanine and Ouabain-Resistance Systems for the
Selection of Induced Mutant Chinese Hamster Cells. MUTAT. RES.,
XXXIII: 261-278, 1975. 36 refs.
Mutagenicity testing -- hamster cells.
81
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Benedict, W. F.
Morphological Transformation and Chromosome Aberrations Produced by Two
Hair Dye Components. NATURE, CCLX: 368-369, 1976. 12 refs.
A possible carcinogenic hazard from hair dyes has been suggested recently
by mutagenicity studies using the Salmonella tester strains developed in
Ames1 laboratory.
Mutagenicity testing noted by chromosome breaks and rearrangement (mouse
cell line).
Bhattacharya, A. K.
Chromosome Damage Induced by Semicarbazide in Spermatocytes of a
Grasshopper. MUTAT. RES., XL: 237-242, 1976. 7 refs.
Semicarbazide hydrochloride (0.1M in glass-distilled water), on injection,
showed mutagenic action on the spermatocyte chromosomes of the
grasshopper, Spathosternum presiniferum. Aberrations such as chromatid
and chromosome breaks, translocations, fragements and bridges were
encountered. The sex chromosome and the long autosomes were affected.
Semicarbazide, perhaps, reacts with DNA and the chromosome in a way
similar to that of hydroxylamine and hydrazines.
Mutagenicity testing - grasshopper spermatocytes.
Bond, D. T-
A System for the Study of Meiotic Non-Disjunction Using Sordaria
bervicollis. MUTAT. RES., XXXVII: 213-220, 1976. 13 refs.
S. bervicollis is potentially useful in studying abnormal chromosome
segregation, e.g., meiotic non-disjunction.
Does this system have a potential as a rapid screen for carcinogenic
substances?
A system is described for the study of abnormal chromosome segregation in
Sordaria brevicollis. The system utilizes two complementing alleles of the
b1 locus on linkage group II. Abnormal asci containing black disomic
asco-spores were detected which fall into two main categories, (a) Non-
disjunctional asci in which the disomic spores were present together with
an equal number of abortive (nulloromic) spores and (b) asci in which an
extra replication of the chromosomes had occurred resulting in pseudo-
wild types being formed without accompanying spore abortion. Calcula-
tions indicate that the non-disjunctkm frequencies at.the first and second
divisions of meiosis are 4.25 X 10" and 4.35 X 10" respectively. It is
suggested that the system is potentially a valuable one both for the study
of meiotic non-disjunction and other causes of aneuploidy.
Mutagenicity testing -- meiotic non-disjunction in S. brevicollis.
Boyd, J. B., et al.
Mutagen sensitivity in X-linked Mutants of D. melanogaster. GENETICS,
LXXXIII: s9, 1976.
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An Abstract.
Mutagenicity testing -- Drosophila melanogaster.
Brewen, T. G., P. Nettesheim and K. P. Jones.
A Host-Mediated Assay for Cytogenetic Mutagenesis: Preliminary Data on
the Effect of Methyl Methane-sulfonate. MUTAT. RES-., X: 645-649,
1970. 5 refs.
Two necessary prerequisites for easy performance of meaningful quantitative
cytogenetic studies on the effect of potential mutagenic agents on
mammalian cells are a homogeneous population of cells and the ability to
expose these cells to the agents in vivo.
Mutagenicity testing -- cytogenic studies using small lymphocytes.
Bridges, B. A.
Modifications of Cellular Mutagenicity Test Procedures. LAB. PRACT.,
XXI: 424, 1972. 4 refs.
In the host-mediated assay, cells are introduced into a mammalian host
which is treated (by another route) with the agent being tested. After
some hours the mammal is killed and the cells recovered and tested in
vitro .for the presence of newly-induced mutants.
The host-mediated assay is only as good as the cell system it utilizes, and
although in principle any cellular system could be used, so far results
and descriptions of technique have only been published for Salmonella and
Neurospara (Legator and Mailing, 1971).
Bridges, B. A., J. Huckle and M. J. Ashwood-Smith.
X-Ray Mutagenesis of Cultured Chinese Hamster Cells. NATURE, CCXXVI:
184-185, 1970. 7 refs.
The development of quantitative systems for the detection of induced gene
mutations in cultured mammalian cells is likely to facilitate work on
hazards from environmental mutagens and on the mechanisms involved in
mutagenesis.
Mutagenicity testing - Chinese hamster cells.
Capizzi, R. L., et al.
The Detection of Chemical Mutagens Using the L5178Y/Asn-murine Leukemia
in Vitro and in a Host-Mediated Assay. CANCER RES., XXXIV:
3073-3082, 1974. 45 refs.
The induction of asparagine-independent mutants by the action of known
chemical mutagens on the asparagine auxotrophy of the murine leukemia
L5178Y (L5178Y/Asn-) was studied.
Mutagenicity testing in murine leukemia cells.
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Carver, J. H., W. C. Dewey and L. E. Hopwood.
X-Ray-Induced Mutants Resistant to 8-azaguanine. 1. Effects of Cell
Density and Expression Time. MUTAT. RES., XXXIV: 447-464, 1976.
43 refs.
This study has attempted to define more clearly the optimal experimental
procedures in regard to cell density and expression time which are
necessary to avoid many of the problems inherent in the AG assay. With
culturing conditions of the assay protocol better understood, the system
holds promise as a useful tool in investigations of environmental mutagens
(chemical as well as X and UV-radiation).
Mutagenicity testing in Chinese hamster ovary cells.
Carver, J. H., W. C. Dewey and L. E. Hopwood.
X-Ray-Induced Mutants Resistant to 8-azaguanine. II. Cell Cycle Dose
Response. MUTAT. RES., XXXIV: 465-480,1976. 48 refs.
These experiments were undertaken to compare the sensitivity of G.. and S
phase to mutation induction by ionizing radiation. The data indicate that
there are no significant differences in response between these two
phases. Relative to radiation protection standards, doubling dose
estimates from cultured cells agrees reasonably well with in vivo studies.
Chinese hamster cells.
Cole, T-, and C. F. Arlett.
Ethyl Methanesulphonate Mutagenesis with L5178Y Mouse Lymphoma Cells:
A Comparison of Ouabain, Thioguanine and Excess Thymidine
Resistance. MUTAT. RES., XXXIV: 507-526, 1976. 32 refs.
We have performed a limited number of host-mediated assays with these
cells. It is clear that while resistance can be induced for all three
selective agents, many deficiencies of the system are apparent. TdR
toxicity is particularly affected by the passage of cells through the host-
compare the possible influence of growth rate on TdR resistance
discussed. There is a much larger inherent variability following treat-
ment in the mouse in both spontaneous and induced levels of resistant
cells. In view of the fact that we elected to use the subcutanteous route
to administer the EMS, we are unable to assume that the dose per cell in
the peritoneal cavity is constant. Differences in penetration from one
mouse to another may well be responsible for the variability in the
induced frequency of resistant variants.
Mutagenicity assayed in mouse lymphoma cells.
Dean, B. J., and D. Blair.
Dominant Lethal Assay in Female Mice After Oral Dosing With Dichlorvos or
Exposure to Atmospheres Containing Dichlorvos. MUTAT. RES., XL:
57-72, 1976. 18 refs.
This communication describes the assay of dominant lethal mutations in
female mice after oral dosing or inhalation exposure to dichlorvos.
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De Marco, A., et al.
Environmental Mutagens and Environmental Factors that can Modify Their
Action. MUTAT. RES., XXIX, 253-454, 1975.
An abstract concerned with mutagens in the environment and environmental
factors that may increase the frequency of induced mutations.
Mutagenesis testing in Drosophila melangaster.
De Serres, F. J., and H. V. Mailing.
Measurement of Recessive Lethal Damage Over the Entire Genome and at
Two Specific Loci in the ad-3 Region of a Two Component Heterokaryon
of Neurospora crassa. CHEM. MUTAGENS: PRIN. METHODS THEIR
DETECT., II: 311-342,1971. 23 refs.
Lethal mutations over the entire genome and in the ad-3 region described in
the following sections are designed primarily for research programs where
the investigator will not only want to obtain precise quantitative data on
mutation induction but will also want to determine the spectrum of
recessive lethal mutations.
Mutagenicity testing in Neurospora crassa.
Ehling, U. H.
Mutagenicity Testing and Risk Estimation With Mammals. MUTAT. RES.,
XLI: 113-122, 1976. 67 refs.
Mammalian test systems are currently used for mutagenicity screening. The
necessity and the limitations of standardizing these methods are discussed
for the dominant-lethal assay. The development of standards for the
controlled use of chemical mutagens should be guided by the experience
accumulated in radiation genetics. Two methods, the measurement of
specific-locus mutation rates in mice and the direct determination of the
phenotypic damage of dominant genes affecting the skeleton of mice, are
recommended for the assessment of the hazard of chemical mutagens.
Fahmy, O. G., and M. J. Fahmy.
Mutagenic Selectivity of Carcinogenic Nitroso Compounds. II. N,N-dim-
ethylnitrosamine. CHEM.-BIOL. INTERACT., XI: 395-412, 1975. 24
refs.
The genetic properties of the hepatocarcinogen N,N-dimethylnitrosamine
(DMN) were examined in Drosophila for the assessment of the role of
dose, cellular metabolism and genie target in its mutagenicity.
Mutagenicity testing in Drosophila.
Hollaender, A., ed.
Chem. Mutagens: Prin. Methods Their Detect., Vol. II. New York:
Plenum Press, 1971.
85
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Measurement of Recessive Lethal Damage Over the Entire Genome and at
Two Specific Loci on the Ad-3 Region of a Two-Component Heterokaryon
of Neurospora crassa
Aspergillus
Higher Plants
Procedures for Culturing Diploid Cells and Preparation of Meiotic
Chromosomes from Dwarf Species of Hamsters
Induction and Analysis of Gene Mutations in Mammalian Cells in Culture
Inducing Mutations with Chemicals in Habrobracon
The Detection of Mutations in Drosophila melanogaster
Root Tips for Studying the Effects of Chemicals on Chromosomes
Cytogenetic Studies in Animals
Specific Locus Mutation in Mice
Dominant Lethal Mutations in Mammals
The Host-Mediated Assay, a Practical Procedure for Evaluating Potential
Mutagenic Agents in Mammals
Human Population Monitoring
Huberman, E., and L. Sachs.
Mutability of Different Genetic Loci in Mammalian Cells of Metabolically
Activated Carcinogenic Poly cyclic Hydrocarbons. PROC. NAT. ACAD.
SCI. USA., LXXIII: 188-192, 1976. 25 refs.
The relationship between carcinogenesis and mutagenesis in mammalian cells
has been determined with 10 polycyclic hydrocarbons with different
degrees of carcinogenicity.
Mutagenicity testing — mammalian cells.
Huberman, E., et al.
Identification of Mutagenic Metabolites of Benzo[a]pyrene in Mammalian
Cells. PROC. NAT. ACAD. SCI. USA, LXXIII: 607-611, 1976. 27
refs.
The mutagenicity of benzofajpyrene and 15 of its derivatives, which
included phenols, the benzo[a]pyrene-4,5-epoxide (the K-region epoxide),
dihydrodiols, two isomeric 7,8-diol-9,10-epoxides, a 6-methyl derivative,
and a 6-hydroxymethyl derivative, were tested with Chinese hamster V79
cells in order to identify the mutagenic metabolites of benzo[a]pyrene.
Mutations were characterized by resistance to ouabain or 8-azaguanine.
Mutagenicity testing in mammalian cells.
Huberman, E., et al.
Mutagenicity to Mammalian Cells of Epoxides and Other Derivatives of
Polycyclic Hydrocarbons. PROC. NAT. ACAD. SCI. USA, LXVIII:
3195-3199, 1971. 25 refs.
The cytotoxicity and mutagenicity of several polycyclic hydrocarbons and
their K-region derivatives were tested in a clone of Chinese hamster
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cells; the production of clones resistant to 8-azaguanine was used as the
marker for mutagenesis.
Mutagenicity testing -- mammalian cells.
Jorgenson, T. A., et al.
Mutagenic Studies of Aziridine Derivatives Derived from Various Diamines.
MUTAT. RES., XXXI: 115-122,1975. 10 refs.
Various aziridine derivatives derived from diamines were studied in several
biological systems to evaluate their effects on reproduction and as
potential mutagens. Considerable variations in the biological activities of
these compounds were seen among animal species and among the varied
chemical structures. In general, mutagenic responses paralleled the
antifertility effects in mice and houseflies and the anticancer effects in
mice. The lack of an antifertility effect by N,N'-bis(aziridinylacetyl) 01,
8-octamethylenediamine in the rat was quite unexpected in view of its
chemosterilant activity in houseflies and mice.
Mutagenicity testing in Coturnix coturnix japonica.
Kamra, O. P.
On the Different Mutagenic Activities of N-alkyl-N'-nitro-N-nitrosoguani-
dines in Higher Plants. MUTAT. RES., XIII: 327-335, 1971. 38
refs.
Mechanisms of action and the differential mutagenic activities of-nitrosoguani-
dines in higher plants are discussed.
Mutagenicity testing in barley.
Kilbey, B. J., F. J. de Serres and H. V. Mailing.
Identification of the Genetic Alteration at the Molecular Level of Ultraviolet
Light-Induced ad-3B mutants in N. crassa. MUTAT. RES., XII:
47-56, 1971. 19 refs.
The correlation between complementation pattern and genetic alteration at
the molecular level found previously by Mailing and de Serres among NA-
and EMS-induced ad-38 mutants, was also found among UV-induced
mutants. Mutants with non-polarized patterns resulted mainly from base-
pair substitutions, whereas mutants with polarized complementation
patterns and noncomplementing mutants are derived from a variety of
genetic alterations.
Mutagenicity testing in Neurospora crassa.
Kirkland, D. J., and S. Venitt.
Cytotoxicity of Hair Colourant constituents: chromosome Damage Induced by
Two Nitrophenylenediamines in Cultured Chinese Hamster Cells.
MUTAT. RES., XL: 47-56, 1976. 15 refs.
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Two aromatic amines are constituent dyes of many widely used proprietary
hair colorants. Both compounds were cytotoxic to CHMP/E cells following
5 days continuous exposure.
Mutagenicity testing in hamster cells.
Legator, M. S., et al.
Cytogenetic Studies in Rats of Cyclohexylamine, a Metabolite of Cyclamate.
SCIENCE, CLXV: 1139-1140, 1969. 10 refs.
Cyclohexylamine, the major known metabolite of cyclamate, was tested in
vivo for possible cytogenetic effects. In rats injected with this
metabolite, there was a direct relation between dose concentration and
percentage of spermatogonial and bone marrow cells showing chromosomal
breaks. Single chromatid breaks predominated with infrequent exchange
figures.
Levin, W., et al.
Carcinogenicity of Benzo[ajpyrene 4,5-,7,8-, and 9,10- Oxides on Mouse
Skin. PR'OC. NAT. ACAD. SCI. USA, LXXIII: 243-247, 1976. 31
refs.
Benzo[a]pyrene and three arene oxides of benzofajpyrene have been tested
for carcinogenicity in mice by topical application of each compound once
every 2 weeks for 60 weeks. The carcinogenic activities of the three
arene oxides of benzo[a]pyrene were not correlated with their stabilities
or mutagenic activities.
Mutagenicity testing in animals.
Liwerant, I. J., and L. H. Pereira Da Silva.
Comparative Mutagenic Effects of Ethyl Methane-Sulfonate, N-methyl-N1-
nitro-N-nitrosoguanidine, Ultraviolet Radiation and Caffeine on
Dictyostelium discoideum. MUTAT. RES., XXXIII: 135-146, 1975. 22
refs.
A high frequency of morphogenetic mutants of D. discoideum can be
induced by treatment with MNNG under conditions which result in
relatively low cell killing. Six temperature-sensitive growth mutants
induced by this treatment were isolated by replica plating. Among these,
five showed spontaneous reversion rates of 10-4 to 10-5. The mutagenic
activity of EMS, measured for the induction of both morphogenetic and
temperature-sensitive mutants, was weaker than that of MNNG and UV
radiation. High frequencies of morphogenetic mutants were obtained only
with doses of UV irradiation and that resulted in high killing of cells or
spores. Caffeine, at concentrations that slightly decreased the growth
rate of amoebae in axenic medium, induced morphogenetic defects and also
enhanced the mutagenic effect of UV irradiation. However, all the
aggregate-less clones derived from caffeine treatment that were studied
reverted to the wild-type phenotype after a variable number of clonal
re-isolations.
Mutagenicity testing in Dictyostelium discoideum.
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Lyon, M. F., R. J. S. Phillips and A. G. Searle.
A Test for Mutagenicity of Caffeine in Mice. MOL. GEN. GENET., XCIII:
7-13, 1962. 22 refs.
1. The results are given of an experiment comparing the specific locus
mutation and rates in male and in female mice having 0.1% caffeine
dissolved in their drinking-water up to the age of 10 weeks. Their
parents had the same treatment from the time of mating, so that tested
germcells might be exposed to caffeine during embryonic development.
2. The mutation rates in males and females did not differ significantly from
each other, nor from the known spontaneous rate; thus, there was no
evidence for induction of mutations by the caffeine treatment. Neither
was there evidence for the induction of dominant lethals following caffeine
treatment of males.
3. The treatment did not noticeably affect reproduction, but some mice
developed aggressive tendencies towards their cage-mates. Some mice
were kept on 0.1% caffeine throughout life: they continued to breed
satisfactorily on the whole.
Mutagenicity testing in mice.
Machemer, L., and D. Lorke.
Evaluation of the Mutagenic Potential of Cyclohexylamine on Spermatogonia
of the Chinese Hamster. MUTAT. RES., XL: 243-250, 1976. 26 refs.
In a cytogenetic study on the spermatogonia of Chinese hamster, cyclo-
hexylsmine (neutral sulphate) was evaluated for mutagenic effects in
comparison with an untreated control group and a group treated with the
mutagenic compound cyclophosphamide, by assessing spermatogonial
metaphases of treated Chinese hamster for chromosomal structural
changes.
Mutagenicity testing in Chinese hamster cells.
Maier, P., and W. Schmid.
Ten Model Mutagens Evaluated by the Micronucleus Test. MUTAT. RES.,
XL: 325-338, 1976. 38 refs.
Ten mutagenic compounds were subjected to the micronucleus bone marrow
test in the mouse. Dose-effect curves were established for all
compounds. With the exception of CTX, COLC and AM, the drugs also
were subjected to chromosome analyses on Chinese hamster fibroblasts in
vitro.
Mutagenicity testing by micronucleus test.
Manual of the First Annual Course in the Principles and Practices of Genetic
Toxicology. Galveston, Texas: Clinical Cancer Center, The
University of Texas Medical Branch, 1976.
Includes papers contributed by:
Bacterial Systems — T. Matney; B. N. Ames, J. McCann and E. Yamasaki
Body Fluid and Tissue Analysis -- M. S. Legator, T. G. Pullin and T. H.
Connor;
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Cell Transformation Technique — B. R. Brinkley and G. M. Fuller
Cytogenetics — T. S. Hsu and F. E. Arrighi; D. J. Kilian and D.
Picciano; W. Schmid; E. Weber, K. Bidwell and M. S. Legator
Dominant Lethal and Translocation Test - S. Green; A Leonard
Drosophila -- S. Zimmering
Environmental Mutagenicity Information Center
Host Mediated Assay — M. S. Legator; R. Fahrig
Mammalian Cells -- R. J. Klebe
Specific Locus Test -- A. G. Searle
Murnik, M. R.
Mutagenicity of Widely Used Herbicides. SCIENCE, LXXXIII: s54, 1976.
An abstract.
Mutagenicity testing in Drosophila melanogaster.
Ong, T.-M., and H. V. Mailing.
Microsomal Activation of Dimethylnitrosamine to Metabolites Mutagenic in
Neurospora crassa. MUTAT. RES., XXXI: 195-196, 1975. 12 refs.
Studies were carried out to determine if the metabolites formed during
incubation DMN in the liver microsome system could induce adenine-3
(ad-3) mutations in Neurospora crassa.
Mutagenicity testing in Neurospora crassa.
Scalera, S. E., and O. G. Ward.
A Quantitative Study of Ethyl Methanesulfonate-Induced Alkylation of Vicia
faba DNA. MUTAT. RES., XII: 71-79, 1971. 27 refs.
A report of the results of a qualitative and quantitative investigation of the
alkylation products formed by the in vitro treatment of Vicia faba root tip
DNA with EMS.
Mutagenicity testing in Vicia faba.
Sung, Z. R.
Mutagenesis of Cultured Plant Cells. GENETICS LXXXIV: 51-57, 1976. 12
refs.
Experiments were designed to study the effectiveness of the chemical
mutagens ethylmethane sulfonate and nitrosoguanidine on plant cells
growing in liquid suspensions. The compounds tested usually increased
mutation frequency by one order of magnitude over the spontaneously
occurring rate, although the increase ranged from one to 140-fold. Cell
killing was found to be directly correlated with mutation frequency.
Mutagenicity testing in plant culture.
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Urwin, C., J. C. Richardson and A. K. Palmer.
An Evaluation of the Mutagenicity of the Cutting Oil Preservative Groton
BK. MUTAT. RES., XL: 43-46, 1976. 7 refs.
The micronucleus test in rats was used to investigate the mutagenic
potential of Grotan BK, a preserving agent used in industrial cutting
oils.
Micronuclei testing.
Valencia, R. A.
Discussion paper: The Use of Drosophila for Mutagenesis Screening. ANN.
N. Y. ACAD. SCI., CCLXIX: 34-36, 1975.
A discussion of mutagenic screening with Drosophila.
Wild, D.
Mutagenicity Studies on Organophosphorus Insecticides. MUTAT. RES.,
XXXII: 133-150, 1975. 50 refs.
This study uses a variety of screening methods.
Zimmering, S.
Utility of Drosophila for Detection of Potential Environmental Chemical
Mutagens. ANN. N. Y. ACAD. SCI., CCLXIX: 26-33, 1975. 52
refs.
The purpose of the communication is to describe some of the advantages of
Drosophila in testing chemicals for mutagenicity in traditional ways and to
explore the possibilities of expanding its role to include testing of
substances derived directly from humans or the human environment.
Mutagenicity testing in Drosophila.
REPORTS, LETTERS AND WORKSHOPS
Ames, B. N.
Letters: Carcinogenicity Tests. SCIENCE, CXCI: 241-245, 1976. 26
refs.
A letter to the Editor regarding carcinogenicity testing and the relationship
of mutagenicity to carcinogenicity.
Ames, B. N., J. McCann and C. Sawyer.
Letters: Mutagens and Carcinogens. SCIENCE, CXCIV: 132-133, 1976. 6
refs.
In reply to Andrew Sivak's comments regarding the use of the Ames1 test
and the correlation or lack of it between mutagenicity and carcinogenicity.
91
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Auerbach, C.
Mutation Research in Microorganisms. MUTAT. RES., V: 198-199, 1968.
The main object of the meeting was to bring together workers engaged in
the same problems in different countries and on different organisms and
not always publishing in the same journals.
Auerbach, C.
Repair and Mutation in Microorganisms. MUTAT. RES., X: 168, 1970. 1
ref.
A brief report of a meeting held in Pisa on mutation in microorganisms.
Auerbach, C.
Symposium No. 2: Mutagenesis Introduction by the Chairman. GENETICS,
LXXVIII: 77-79, 1974.
Chairperson's opening remarks on mutagenicity.
Brookes, P., and F. J. de Serres.
Report of the Workshop on the Mutagenicity of Chemical Carcinogens.
MUTAT. RES., XXXVIII: 155-160, 1976.
The workshop was organized by the U.S. and the Japanese Environmental
Panels in the U.S.-Japan Cooperative Medical Science Program to review
the status of experiments in the U.S. and Japan to determine the
correlation between carcinogenic and mutagenic activity.
Center for the Biology of Natural Systems. (Commoner, B.)
Reports on EPA Grant No. R-804395-01-0, "Studies to Improve the
Reliability and Sensitivity of Bacterial Mutagenesis as a Screen for
Environmental Carcinogens," St. Louis, Missouri: Washington
University, April-November, 1976.
Committee 17, Environmental Mutagen Society. Report of the Committee.
Environmental Mutagenic Hazards. SCIENCE, CLXXXVIII: 503-514,
1975.
The characteristics of mutational screens such as bacterial, fungal, plant,
insect, mammalian cell culture and animal tests are discussed relative to
the feasibility of using them as screens for chemicals entering the
environment.
de Serres, F. J.
Mutagenicity of Chemical Carcinogens. MUTAT. RES., XLI: 43-50, 1976.
7 refs.
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During the past three years, two collaborative studies were started in the
U.S. and Japan to study the correlation between carcinogenic and
mutagenic activity. The objective of the collaborative studies was to test
known chemical carcinogens, non-carcinogenic structural analogs and
other non-carcinogens, with a variety of assay systems for mutagenicity.
A series of reports of meetings and workshops.
de Serres, F. J.
The Correlation Between Carcinogenic and Mutagenic Activity in Short-Term
Tests for Mutation-Induction and DNA Repair. MUTAT. RES., XXXI:
203-204, 1975.
An editorial. A report of three workshops which discussed testing,
particularly short-term, and the correlation between carcinogenic and
mutagenic activity.
Goetz, P.
Symposium on the Mutagenicity Testing of Environmental Contaminants.
MUTAT. RES., XXXI: 129-130, 1975.
A report on Czechoslovakian symposium dealing with environmental mutagens.
Hollaender, A.
Opening Remarks. ANN. N. Y. ACAD. SCI., COLXIX: 1-3, 1975.
Remarks on mutagens and potential carcinogens.
Knaap, A. G. A. C., P. G. N. Kramers, and F. H. Sobels.
Workshop on Chemical Mutagenesis in the Netherlands. MUTAT. RES.,
XXXVIII: 239, 1976.
Notes on the mutagens workshop in the Netherlands in 1975.
Ramel, C.
Mutagenicity Research and Testing in Sweden. MUTAT. RES., XXXIII:
79-86, 1975. 22 refs.
A survey is given of Swedish legislation for control chemicals in the
environment.
An outline is given of the organization of the Environmental Toxicology Unit
of the Wallenberg laboratory, University of Stockholm.
As examples of projects under joint investigation, results on polychlorinated
biphenyl (PCB) and on vinyl chloride are briefly described.
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Rubin, H.
Letters: Carcinogenicity Tests. SCIENCE, CXCI: 241, 1976. 11 refs.
A letter to the editor regarding carcinogenicity testing.
Sermonti, G.
"Ettore Majorana" Centre for scientific culture, international school of
general genetics (A NATO Adv. Study Inst.). MUTAT. RES.,
XXXVIII: 161-162, 1976.
A course in environmental mutagenesis emphasized the use of bacteria and
other microorganisms as the most sensitive, specific and short-term
approach to the evaluation of chemical mutagenesis.
On the other hand, Drosophila had several distinct advantages, in that it
permits the assessment of the total genetic spectrum and does not require
activating systems, as do some bacterial systems.
Test systems for mutagenicity range from short-term assays on bacteria and
eukaryotic microorganisms to tests for recessive lethals in Drosophila, to
cytological observations on somatic and germ cells in vivo and in vitro, to
dominant lethal and specific locus tests in rodents.
Sivak, A.
The Ames Assay. SCIENCE, CXCIII: 272-273, 1976. 6 refs.
The Ames assay will continue to be useful as one of a battery of first-step
prescreens for chemical agents that may have the potential for interacting
with cellular genomes. However, the implication that positive results in
this microbial mutagenesis system will correspond to carcinogenicity in
experimental animals or in humans does not appear, at present, to be
substantiated.
The European Environmental Mutagen Society.
Abstracts of Papers presented at the 5th Annual Meeting, Florence, Italy,
1975. 64 abstracts.
University of Alberta, et al.
Workshop on Mutagenesis and Predictive Carcinogenesis. Edmonton,
Alberta, Canada, 1977.
The Workshop is designed to provide a detailed appreciation of techniques
used in screening for environmental mutagens and potential carcinogens,
together with background understanding of the problems involved.
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EVALUATION OF ASSAY SYSTEMS FOR ENVIRONMENTAL CARCINOGENS
AND/OR MUTAGENS
Bartsch, H.
Predictive Value of Mutagenicity Tests in Chemical Carcinogenesis, MUTAT.
RES., XXXVIII: 177-190, 1976. 68 refs.
Although there are still many problems involved in the interpretation of
results of mutagenicity testing in terms of evaluating the carcinogenicity
of chemicals, short-term tests can already be used in detecting possible
cancer-causing agents with a sensitivity which did not exist ten years
ago. They could thus be a powerful tool, when used in combination with
epidemiological studies, in environmental control.
Bochkov, N. P., et al.
System for the Evaluation of the Risk from Chemical Mutagens for Man:
Basic Principles and Practical Recommendations. MUTAT. RES.,
XXXVIII: 191-202, 1976. 23 refs.
A testing system is recommended that permits: (1) reduction in cost and
time, (2) analysis of gene and chromosome mutations in germ and somatic
cells, (3) evaluation of mutagenic effects of a chemical substance and its
metabolites, (4) guarantee of the minimal variability between separate
experiments and (5) evaluation of the dose-effect relationship.
Bridges, B. A.
Evaluation of Mutagenicity and Carcinogenicity Using a Three-Tier System.
MUTAT. RES., XLI: 71-72, 1976. 6 refs.
The first tier contains short-term screening tests with sub-mammalian
systems, the second tier contains short-and longer-term tests with whole
mammals, and the third tier involves a risk-benefit evaluation which may
entail further more specialized testing procedures and experiments on the
detailed metabolism of the agent in vivo.
Bridges, B. A.
Short Term Screening Tests for Carcinogens. NATURE, CCLXI: 195-200,
1976. 81 refs.
There are short term tests with a high predictive value for mammalian
carcinogens. Many of them are based on the ability to detect damage to
DNA in bacteria or mammalian cells after metabolic activation by
microsomal enzymes. They will enable provisional safety assessments to
be made of industrial and environmental chemicals.
95
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Commoner, B.
Mutagenesis: A Probe for Carcinogenicity. HOSP. PRACT., (March):
43-44, 50, 1975.
A number of substances that are powerful carcinogens in laboratory animals
are inactive as bacterial mutagens. Carcinogenic activity of a given
substance often varies with the test species or even within a species, so
it is difficult to arrive at a meaningful definition of carcinogenic activity,
especially as it relates to people.
Commoner, B.
Reliability of Bacterial Mutagenesis Techniques to Distinguish Carcinogenic
and Noncarcinogenic Chemicals. Report to the U.S. Environmental
Protection Agency, Office of Research and Development, April, 1976.
Washington, D. C.: U.S. Environmental Protection Agency, 1976. 5
ref s.
The purpose of these investigations was to determine the reliability with
which an expanded Salmonella mutagenesis test system can distinguish
between those organic chemical substances that cause cancer in laboratory
animals and those that do not. One Hundred organic compounds were
tested, 50 presumptive carcinogens and 50 noncarcinogens.
In general the results indicate that the Salmonella mutagenesis system can
be used to distinguish, with a high degree of reliability, that the
statistical reliability needs to be improved for application to environmental
samples and the steps that need to be taken to improve the test.
Commoner, B.
Tests of the Reliability With Which the Bacterial Mutagenesis Technique Can
Distinguish Between Carcinogenic and Noncarcinogenic Synthetic
Organic Chemicals. Report to the Environmental Protection Agency,
Contract No. 68-01-2471, May, 1976. 13 refs.
Tests were made of 100 organic compounds, 50 presumptive carcinogens and
50 noncarcinogens. The results indicate that the Salmonella mutagenesis
system can be used to distinguish, with a high degree of reliability,
between presumptive carcinogens and noncarcinogens, in populations of
test samples with two classes of compounds in equal proportions. The
results also show that the statistical reliability of the system needs to be
improved for application to those populations of environmental samples in
which the proportion of active substances may be relatively low, as well
as the steps needed to make the improvements:
Conference on Occupational Carcinogenesis.
Discussion. Carcinogenesis in the Metal Industry. Conference on
Occupational Carcinogenesis, N. Y. Academy of Sciences, New York,
May, 1975. In ANN. N. Y. ACAD. SCI., CCLXXI: 496-504, 1976.
96
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Conference on Occupational Carcinogenesis.
Discussion. Chemical Carcinogenesis (I). Conference on Occupational
Carcinogenesis, N. Y. Academy of Sciences, New York, May, 1975. In
ANN. N. Y. ACAD. SCI., CCLXXI: 473-480, 1976.
Conference on Occupational Carcinogenesis.
Discussion. Chemical Carcinogenesis (II). Conference on Occupational
Carcinogenesis, N. Y. Academy of Sciences, New York, May, 1975. In
ANN. N. Y. ACAD. SCI., CCLXXI: 481-488, 1976.
Conference on Occupational Carcinogenesis.
Discussion. Current Concepts of Carcinogenesis. Conference on Occupa-
tional Carcinogenesis, N. Y. Academy of Sciences, New York, May,
1975. In ANN. N. Y. ACAD. SCI., CCLXXI: 460-472, 1976.
Conference on Occupational Carcinogenesis.
Discussion. High-Risk Industrial Groups: Identification, Education and
Surveillance. Conference on Occupational Carcinogenesis, N. Y.
Academy of Sciences, New York, May, 1975. In ANN. N. Y. ACAD.
SCI., CCLXXI: 508-612, 1976.
Conference on Occupational Carcinogenesis.
Discussion. Methodologies for Risk Assessment. Conference on Occupa-
tional Carcinogenesis, N. Y. Academy of Sciences, New York, May,
1975. In ANN. N. Y. ACAD. SCI., CCLXXI: 513-516, 1976.
Conference on Occupational Carcinogenesis.
Discussion. Prevention of Occupational Cancer-Toward an Integrated
Program of Governmental Action. Conference on Occupational
Carcinogenesis, N. Y. Academy of Sciences, New York, May, 1975. In
ANN. N. Y. ACAD. SCI., CCLXXI: 491-495, 1976.
Conference on Occupational Carcinogenesis.
Discussion. Radiation and Particulate Matter. Conference on Occupational
Carcinogenesis, N. Y. Academy of Sciences, New York, May, 1975. In
ANN. N. Y. ACAD. SCI., CCLXXI: 505-507, 1976.
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Conference on Occupational Carcinogenesis.
Discussion. Recent Approaches to the Control of Carcinogenic Exposures.
Conference on Occupational Carcinogenesis, N. Y. Academy of
Sciences, New York, May, 1975. In ANN. N. Y. ACAD. SCI.,
CCLXXI: 489-490, 1976.
Dean, B. J.
A Predictive Testing Scheme for Carcinogenicity and Mutagenicity of
Industrial Chemicals. MUTAT. RES., XLI: 83-88, 1976. 4 refs.
A general discussion. Mutagenicity screening.
de Serres, F. J.
Perspective in a Period of Transition. MUTAT. RES., XXXVIII: 355-358,
1976.
During the past year there have been two major developments that will have
an enormous impact on the work of this Society in the near future. The
first was the identification of many environmental and industrial chemicals
as carcinogens and the widespread belief that a high percentage (80-90%)
of human cancer is a result of such exposures. The second was a
demonstration of a high correlation between carcinogenic and mutagenic
activity in newly developed short-term tests for mutagenicity. The latter
finding has enormous implications for the first, because it opens up the
possiblity to utilize the short-term tests not only to identify potential
mutagens in our enviroment but potential carcinogens as well.
de Serres, F. J.
Prospects for a Revolution in the Methods of Toxicological Evaluation.
MUTAT. RES., XXXVIII: 165-176. 39 refs.
There is a realization that many man-made chemicals have potent mutagenic
activity and there is concern over their effects on man. Genetic
toxicology focuses on biological activity harmful to man and his offspring.
de Serres, F. J.
The Utility of Short-Term Tests for Mutagenicity MUTAT. RES., XXXVIII:
1-2, 1976. 3 refs.
A thesis based on the need to screen environmental chemicals for
mutagenicity. Short-term tests should be considered assays for potential
mutagenic activity in man and as a highly efficient mechanism both for
screening activity of environmental agents and establishing priorities for
further testing.
98
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de Serres, F. J.
The Utility of Short-Term Tests for Mutagenicity in the Toxicological
Evaluation of Environmental Agents. MUTAT. RES., XXXIII: 11-15,
1975.
By using the short-term tests to establish priorities for testing in higher
organisms, we can develop a more extensive data base from tests on
hundreds of compounds.
Drake, J. W.
Environmental Mutagenesis: Evolving Strategies in the USA. MUTAT.
RES., XXXIII: 65-72, 1975.
The "Committee 17" report made recommendations regarding the screening of
environmental mutagens and the use of the resulting data. It is
important to employ highly sensitive tests which detect heritable genetic
damage of all possible molecular types. Mutagens of artificial origin which
are being considered for continued production must be characterized with
respect to level and pattern of distribution and persistence in the
environment. Finally, the Committee laid out specific recommendations
concerning maximum permissible exposures to environmental mutagens.
Epler, J. L.
Panel 4: Synfuel Utilization: Environmental and Health Effects. For
publication in: PROC. SYMP. MANAGEMENT OF RESIDUALS FROM
SYNTHETIC FUELS PRODUCTION, Denver, Colorado, 1976. 11 refs.
A discussion of mutagenicity screening.
Kolata, G. B.
Chemical Carcinogens: Industry Adopts Controversial "Quick" Tests.
SCIENCE, CXCII: 1215-1217, 1976.
In support of the Ames Test (Salmonella mutagens) as a screen for
environmental chemical carcinogens.
Legator, M. S., and S. Zimmering.
Integration of Mammalian, Microbial and Drosophila Procedures for
Evaluating Chemical Mutagens. MUTAT. RES., XXIX: 181-188, 1975.
23 refs.
The incorporation of a mutagenicity protocol as a part of an overall
toxicological program required or advocated by regulatory agencies in the
U.S. has yet to be realized.
Three screening procedures for environmental carcinogens are discussed.
99
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Purchase, I. F. H., et al.
Evaluation of Six Short-Term Tests for Detecting Organic Chemical Carcino-
gens and Recommendations for Their Use. NATURE, CCLXIV: 624-
627, 1976. 18 refs.
Six short-term tests for detecting carcinogenicity have been evaluated using
120 compounds, of which half were carcinogens and the rest non-
carcinogens. The results obtained indicate that the Ames test and a
"cell transformation" assay are both sufficiently sensitive to carcinogeni-
city, or the lack of it, in the compounds studied to enable them to be
employed for detecting potential carcinogens. The consequences of using
short term tests under various screening conditions have been explored.
In order to have confidence in the results obtained for new or previously
untested compounds it is important to use such tests in a carefully
controlled manner.
Sobels, F. H.
Some Thoughts on the Evaluation of Environmental Mutagens. MUTAT.
RES., XXXVIII, 361-366, 1976. 10 refs.
Chemical compounds in ever-increasing variety and kind are constantly
being introduced into the human environment. Some of these may
adversely affect the genetic material. Such effects deserve attention not
only for reasons of protecting the genetic constitution of future genera-
tions, but are also of prime and direct concern to the present, in view of
the strking concordance between the carcinogenic and mutagenic potential
of most chemicals. That is, recent results with microbial assay systems
and with Drosophila have convincingly demonstrated that the great
majority of compounds capable of producing malignant transformation are
also effective in inducing genetic changes in the form of heritable
mutations. A task of immediate concern thus becomes one of how such
genetic and carcinogenic hazards can be avoided and how adequate
regulations to minimize exposure should be formulated.
Stich, H. F., et al.
The Search for Relevant Short-Term Bioassays for Chemical Carcinogens:
the Tribulation of a Modern Sisyphus. CAN. J. GENET. CYTOL.,
VII: 471-492, 1975. 26 refs.
Based on a good correlation between carcinogenicity and mutagenic activity,
several rapid microbial bioassays for chemical carcinogens have been
recently developed. We would like to suggest, that these microbial tests
should be followed by bioassays using cultured human cells of the
"average" man, and of persons with elevated cancer risk or increased
susceptibility to carcinogenic agents.
Zeigler, E., and J. Springer.
Storage and Statistical Evaluation of Microbial Mutagenicity Data. MUTAT.
RES., XXXI: 337, 1975.
An abstract. Statistical evaluation of the Ames Test (Salmonella).
100
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MISCELLANEOUS
Auerbach, C.
The Effects of Six Years of Mutagen Testing on Our Attitude to the
Problems Posed by It. MUTAT. RES., XXXIII: 3-10, 1975. 22 refs.
Progress has been amazingly rapid both in technical means for the detection
of mutagens and in the understanding of the basic process of muta-
genesis. There has also been much feedback in both directions, to the
profit of both areas of research.
Auerbach, C.
History of Research on Chemical Mutagenesis. CHEM. MUTAGENS: PRIN.
METHODS THEIR DETECT., II: 1-19, 1973. 4 refs.
Auerbach, C.
Some Old Problems in Mutagenesis and Their Bearing on Mutagen Testing.
MUTAT. RES., XLI: 3-6, 1976.
The paper points up some problems that, after having been discussed for
many years, now gain new importance through their relevance for
mutagen testing.
Bender, D. F., M. L. Peterson, and H. Stierli, eds.
Physical, Chemical and Microbiological Methods of Solid Waste Testing.
Report to the U.S. Environmental Protection Agency Office of Research
and Monitoring, Cincinnati, Ohio, May, 1973. Cincinnati, Ohio:
Office of Research and Monitoring, National Environmental Research
Center, 1973. 20 refs.
This publication is a compilation of methods used by the Solid Waste
Research Laboratory of the National Environmental Research Center in
Cincinnati, Office of Research and Monitoring, U.S. Environmental Protec-
tion Agency, to perform various physical, chemical, and microbiological
analyses in the field of solid waste management.
Berenblum, I.
Possible Relationships Between Mutagenesis and Carcinogenesis. ENVIRON.
SCI.: AN INTERDISCIPLINARY MONOGRAPH SERIES, 177-183, 1972.
20 refs.
A discussion of chemical carcinogens in reference to the relationship
between mutagens and carcinogens.
Bridges, B. A.
Environmental Genetic Hazards -- The Impossible Problem? ECOLOGIST, I:
19-21, 1971.
Environmental pollution and attendant genetic hazards.
101
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Bridges, B. A.
The Mutagenicity of Captan and Related Fungicides. MUTAT. RES.,
XXXII: 3-34, 1975. 70 refs.
Review of chemical mutagenesis in bacteria, eukaryotic cells, higher
organisms, etc., and recommendations.
Bridges, B. A.
A Review of the Committee 17 Report. MUTAT. RES., XXXI: 255-257,
1975.
Environmental mutagenesis -- EMS Committee.
Bridges, B. A.
Screening for Environmental Agents Causing Genetic Damage: Introduction.
LAB. PRACT., XXI: 411-412, 1972. 7 refs. "
A substantial proportion of disease in man can be attributed to genetic
damage to cells, both somatic and germ cells. Heritable mutations can be
induced by both radiations and chemicals. It is likely that safety
requirements for food additives, Pharmaceuticals, pesticides and environ-
mental pollutants will in future include tests for mutagenicity. The
following four papers describe simple cellular systems which detect
heritable genetic damage.
Bridges, B. A.
The Three-Tier Approach to Mutagenicity Screening and the Concept of
Radiation Equivalent Dose. MUTAT. RES., XXVI: 335-340, 1974. 3
refs.
A three-tier approach to mutagenicity screening is proposed, based on 3
general principles. The object would be to carry out experiments
designed to give a quantitative indication of the potential risk to man
followed by a risk-benefit assessment. It is suggested that one way of
comparing the effect of one agent with that of another might be to
express it as a radiation-equivalent dose (in RADEQUIV units).
Bridges, B. A., and J. G. Stamper.
Hypothetical Dose-Response Curves for Chronic Exposures to Mutagens or
Carcinogens Subject to Simple Enzymatic Detoxification in the
Mammalian Body. MUTAT. RES., XXXIII: 87-91, 1975. 6 refs.
Dose-response curves for chemical carcinogenesis and mutagenesis in the
whole mammal may be influenced (a) by processes affecting the delivery
of the applied dose to the DNA of the target cell or (b) by processes
affecting the response of the cell to the initial DNA damage.
102
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Care of the Environment in Scandinavia, Special Issue, SCAND. REV.,
LXIV: 1976.
Chadwick, K. H., and H. P. Leenhouts.
The Correlation Between Mutation Frequency and Cell Survival Following
Different Mutagenic Treatments. THEOR. APPL. GENE., XLVII: 5-8,
1976. 21 refs.
A direct mathematical relationship between mutation frequency per survivor
and cell survival is derived from theoretical considerations of the
molecular effects of radiation in a cell. The mathematical relationship is
independent of the way in which the lesion which leads to mutations and
cell death is induced, so the analysis has consequently been applied to
other mutagenic treatments such as UV light and chemicals. It is
concluded that, although the lesions induced by chemicals may not be the
same as those induced by radiation, it is probable that for the chemicals
considered common basic damage to the DNA molecule is implicated as the
critical lesion.
Clark, A. M.
Naturally Occurring Mutagens. MUTAT. RES., XXXII: 361-374, 1976. 50
refs.
Naturally occurring mutagens have usually been discovered as a result of
outbreaks of disease in agriculture livestock, or as a result of epidemio-
logical studies of cancer of the liver in man. Subsequent work has then
shown that the toxic agents responsible often have mutagenic properties.
Commonly the toxic agent itself does not show high biological activity,
but after ingestion it is converted by metabolic processes into the active
mutagen or carcinogen.
Clarke, C. H.
Giant Hogweed Sap: Another Environmental Mutagen. MUTAT. RES.,
XXXI: 63-64, 1975. 10 refs.
The sap of the Giant Hogweed (Heracleum mentagazianum) causes severe
blistering of human skin on exposure to sunlight. The active principles
are furocoumarins. In view of the fact that 8-methoxypsoralen plus long
wavelength ultraviolet light (LUV) has been shown to be mutagenic in
bacteria tested in an E. coli, fluorescent light is also used.
Commoner, B.
Cancer as an Environmental Disease. HOSP. PRACT., (February): 82-84,
1975.
Prevention of disease is one of the most powerful motivations for improving
the environment; and among the growing roster of environmental diseases,
one is beginning to emerge as predominant: cancer.
103
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Commoner, B.
Carcinogens in the Environment. CHEM. TECHNOL., (February): 76-82,
1977. 9 refs.
It would appear that the opportunity now exists to develop a new strategy
for controlling the growing problem of environmental cancer. It would
begin with detecting presumptive carcinogens in environmental samples,
identifying them and tracing their movements in the environment by means
of screening based on bacterial mutagenesis. Then by determining the
mutagenicity of human urine samples it may be possible to determine
which of these presumptive carcinogens represent carcinogenic risks to
people. With such information in hand, it would be possible to reduce
this risk by tracing environmental carcinogens back to their origins, and
then taking the final, and most difficult step -- regulating environmental
emissions-that will, at last, prevent the disease.
Commoner, B.
Comments on Measures of Mutagenic Activity. Unpublished, St. Louis,
Missouri: Washington University, 1976.
There is at present a good deal of confusion regarding the terms in which
the mutagenic activity of a substance should be measured in the Ames
test. By using the same data, Sivak seemingly demonstrates the reverse.
The question arises, then, as to whether the latter measure is, in fact, a
valid index of the comparative mutagenic activity of different compounds
in the Salmonella system.
Drake, J. W.
The Molecular Basis of Mutations. San Francisco: Holden-Day, 1970.
This book presents a broad outline of what is understood about mutational
mechanisms and also to emphasize many of the doubtful areas.
Drake, J. W., and R. H. Baltz.
The Biochemistry of Mutagenesis. ANN. REV. BIOCHEM., XLV: 11-37,
1976. 228 refs.
A review of mutagenesis.
Drake, J. W., and W. G. Flamm.
The Molecular Basis of Mutation. ENVIRON. SCI.: AN INTER-
DISCIPLINARY MONOGRAPH SERIES, 15-26, 1972.
Introduction toward the understanding of the mutation process.
104
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Elias, P. S.
The Medical Significance of Marine Pollution by Organic Chemicals. PROC.
R. SOC. LOND, B., CLXXXIX: 443-458, 1975. 13 refs.
A discussion of mutagenicity and carcinogenicity relative to chemical
pollutants.
Epstein, S. S.
Environmental Determinants of Human Cancer. CANC. RES., XXXIV:
2425-2435, 1974. 85 refs.
A general discussion of chemical carcinogens.
Epstein, S. S., and M. S. Legator.
The Mutagenicity of Pesticides. Cambridge, Mass.: MIT Press, 1971.
This monograph is based on the Report of the Advisory Panel on
Mutagenicity of Pesticides to the Secretary's Commission on Pesticides and
Their Relationship to Environmental Health, HEW (GPO, December 1969).
Farber, E.
Chemical Carcinogenesis. CURR. .RES. ONCOLOGY, 95-123, 1972. 30 refs.
A discussion of chemical carcinogenesis.
Fishbein, L.
Atmospheric Mutagens. CHEM. MUTAGENS: PRIN. METHODS THEIR
DETECT. IV: 219-319, 1976. 606 refs.
Comparative data (where available) has been presented on the relative
amounts, residues, and transport in the atmosphere of a spectrum of
mutagenic and potential mutagenic agents from diverse categories,
including anthropogenic sources of air pollution, pesticidal and industrial
use categories and their degradation products, as well as a number of
naturally occurring pollutant and aerosol contributors.
Fishbein, L.
Atmospheric Mutagens. I. Sulfur Oxides and Nitrogen Oxides. MUTAT.
RES., XXXII: 309-330,1976. 144 refs.
A discussion of atmospheric chemical contaminants.
Fishbein, L.
Industrial Mutagens and Potential Mutagens. I. Halogenated Aliphatic
Derivatives. MUTAT. RES., XXXII: 267-308, 1976. 242 refs.
105
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A discussion of potential industrial mutagens from the standpoint of environ-
mental toxicology.
Flamm, W. G.
A Tier System Approach to Mutagen Testing. MUTAT. RES., XXVI:
329-333, 1974. 20 refs.
This approach to testing involves-the employment of a hierarchical system of
tests that is referred to as a tier system. The first tier is a prescreen,
utilizing microbial organisms coupled to mammalian metabolic activation
systems. Substances found to be mutagenic are presumed mutagens and
subjected to further testing. Substances positive in both tier one and
two are assumed to be mutagens in the qualitative sense.
Fraser, F. C.
Non-Scientific Influences on Decisions Concerning Human Chemical
Exposure - a personal commentary. MUTAT. RES., XXXIII: 93, 1975.
It would be nice if interests based on economic, political or emotional
involvement had no opportunity to influence the judgement of those who
formulate policy decisions relating to environmental hazards.
Gelboin, H. V.
Carcinogens, Enzyme Induction and Gene Action. ADV. CANCER RES., X:
1-81, 1967. 203 refs.
A large segment of this review concerns the effect of polycyclic hydro-
carbons and drugs on the level of certain enzyme activities.
Gletten, F., U. Weekes and D. Brusick.
In Vitro Metabolic Activation of Chemical Mutagens. 1. Development of an
In Vitro Mutagenicity Assay Using Liver Microsomal Enzymes for the
Activation of Dimethylnitrosamine to a Mutagen. MUTAT. RES.,
XXVIII: 113-122, 1975. 22 refs.
Qualitative and quantitative assays were developed to study the in vitro
enzymatic activation of dimethylnitrosamine (DMNA) to its mutagenic form.
A comparison between two inbred mouse strains using the in vitro activa-
tion assay demonstrated that this technique might be a useful tool in
quantitatively measuring differences in genetically influenced levels of
DMNA metabolism in individual animals and their tissues.
Harnden, D. G.
Chromosome Abnormalities and Predisposition Towards Cancer. PROC.
ROY. SOC. MED., LXIX: 41-43, 1976. 22 refs.
A short essay on chromosome damage.
106
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It seems reasonable to suggest that a chromosome damaging agency whether
chemical, physical or biological should be regarded as a potential
carcinogen, but the induction of chromosome damage does not necessarily
mean that malignancy will ensue.
Heddle, J. A.
The Regulation of Human Exposure to Mutagens Amidst Scientific
Controversy. MUTAT. RES., XXXIII: 103-105, 1975.
Three topics central to the problem of regulating human exposure are (1)
the impact of an increased mutation rate upon the human population, (2)
the shape of the dose response curve, and (3) the adequacy of
procedures used to identify compounds that are mutagenic in man.
Hirschhorn, K.
Discussion paper: The Role of Cytogenetics in Mutagenesis Testing. ANN.
N. Y. ACAD. SCI., CCLXIX: 12-15, 1975. 9 refs.
A discussion pertaining to cytogenic testing of mutagens.
Hollaender, A., ed.
Chem. Mutagens: Prin. Methods Their Detect., Vol. I. New York:
Plenum Press, 1971.
Molecular mechanisms of mutations
Correlation between teratogenic and mutagenic effects of chemicals in
mammals
The mutagenicity of chemical carcinogens: Correlations, problems and
interpretations
Effects on DNA: Chemical methods
Physical-chemical methods for the detection of the effect of mutagens on DNA
Effects on DNA: Transforming principle
Mutagen screening with virulent bacteriophages
Prophage induction in lysogenic bacteria as a method of detecting potential
mutagenic, carcinogenic, carcinostatic and teratogenic agents
The detection of chemical mutagens with enteric bacteria
Mutagenesis studies with E. coli mutants with known amino acid (and base-
pair) changes
Mutation induction in yeast
Hollaender, A., ed.
Conclusion. CHEM. MUTAGENS: PRIN. METHODS THEIR DETECT., II:
607-610, 1971.
Summary and conclusions on the work presented in this volume.
Measurement of recessive lethal damage over the entire genome and at two
specific loci in the ad-3 region of a two-component heterokaryon of
Neurospora crassa
107
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Aspergillus
Higher plants
Procedures for culturing diploid cells and preparation of meiotic
chromosomes from dwarf species of hamsters
Induction and analysis of gene mutations in mammalian cells in culture
Inducing mutations with chemicals in Habrobracon
The detection of mutations in Drosophila melanogaster.
Root tips for studying the effects of chemicals on chromosomes
Cytogenetic studies in animals
Specific locus mutation in mice
Dominant lethal mutations in mammals
The host-mediated assay, a practical procedure for evaluating potential
mutagenic agents in mammals.
Human population monitoring
Hollaender, A., ed.
Chem. Mutagens: Prin. Methods Their Detect.,' Vol. III. New York:
Plenum Press, 1973.
History of research on chemical mutagenesis
Observations on meiotic chromosomes of the male mouse as a test of the
potential mutagenicity of chemicals in mammals.
Techniques for monitoring and assessing the significance of mutagenesis in
human populations
Specific-locus mutational assay systems for mouse lymphoma cells
Approaches to monitoring human populations for mutation rates and mutation
rates and genetic disease
Repair of chemical damage to human DNA
Tradescantia stamen hairs: A radiobiological test system applicable to
chemical mutagenesis
Detection of genetically active chemicals using various yeast systems
Total reproductive capacity in female mice: Chemical effects and their
analysis
Insect chemosterilants as mutagens
The literature of chemical mutagenesis
Hollaender, A., ed.
Chem. Mutagens: Prin. Methods Their Detect., Vol. IV- New York:
Plenum Press, 1976.
Cytological methods for detecting chemical mutagens
The micronucleus test for cytogenetic analysis
Numerical sex-chromosome anomalies in mammals: Their spontaneous
occurrence and use in mutagenesis studies
The function of Drosophila in genetic toxicology testing
Plant test systems for detection of chemical mutagens
The use of indirect indicator systems to detect mutagenic activity in human
subjects and experimental animals
Carcinogenic and mutagenic N-nitroso compounds
Atmospheric mutagens
Cytogenetic surveillance of industrial populations
108
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Hong, S.-J., and L. H. Piette.
Electron Spin Resonance Spin-Label Studies of Intercalation of Ethidium
Bromide and Aromatic Amine Carcinogens in DNA. CANCER RES.,
XXXVI: 1159-1171, 1976. 48 refs.
These studies have demonstrated the feasibility of the spin-label technique
as a powerful tool for providing not only clear-cut evidence of physical
binding but also information such as base-preferential binding and the
postbinding structural changes of the host DNA molecule. Moreover,
carcinogenic and mutagenic activity of most of the carcinogens used were
found to persist even after attachment of the nitroxide reporter on the
respective ligand molecule.
We believe that the technique is a highly promising tool in studying these
very important aspects.
IARC Monographs.
Evaluation of Carcinogenic Risk of Chemicals to Man. Vol. 1. Lyon,
France: IARC, 1972.
IARC Monographs.
Evaluation of Carcinogenic Risk of Chemicals to Man. Vol. 2: Some
Inorganic and Organometallic Compounds. Lyon, France: IARC, 1973.
IARC Monographs.
Evaluation of Carcinogenic Risk of Chemicals to Man. Vol. 3: Certain
Poly cyclic Aromatic Hydrocarbons and Heterocyclic Compounds. Lyon,
France: IARC, 1973.
IARC Monograps.
Evaluation of Carcinogenic -Risk of Chemicals to Man. Vol. 4: Some
Aromatic Amines, Hydrazine and Related Substances, N-nitroso
Compounds and Miscellaneous Alkylating Agents. Lyon, France:
IARC, 1974.
IARC Monographs.
Evaluation of Carcinogenic Risk of Chemicals to Man. Vol. 5: Some
Organochlorine Pesticides. Lyon, France: IARC, 1974.
IARC Monographs.
Evaluation of Carcinogenic Risk of Chemicals to Man. Vol. 6: Sex
Hormones. Lyon, France: IARC, 1974.
109
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IARC Monographs.
Evaluation of Carcinogenic Risk of Chemicals to Man. Vol. 7: Some
Antithyroid and Related Substances, Nitrofurans and Industrial
Chemicals. Lyon, France: IARC, 1974.
IARC Monographs.
Evaluation of Carcinogenic Risk of Chemicals to Man. Vol. 8: Some
Aromatic Azo Compounds. Lyon, France: IARC, 1975.
IARC Monographs.
Evaluation of Carcinogenic Risk of Chemicals to Man. VoL 9: Some
Aziridines, N-, S- and O- Mustards and Selenium. Lyon, France:
IARC, 1975.
IARC Monographs.
Evaluation of Carcinogenic Risk of Chemicals to Man. Vol. 10: Some
Naturally Occurring Substances. Lyon, France: IARC, 1976.
IARC Monographs.
Evaluation of Carcinogenic Risk of Chemicals to Man. Vol. 11: Cadmium,
Nickel, Some Expoxides, Miscellaneous Industrial Chemicals and General
Considerations on Volatile Anaesthetics. Lyon, France: IARC, 1976.
Janerich, D. T., and C. E. Lawrence.
Epidemiological Strategies for Identifying Carcinogens. MUTAT. RES.,
XXXIII: 55-63, 1975. 20 refs.
Neither epidemiological techniques, nor laboratory techniques, seem to be
providing specific new developments which could lead to a so-called
"break-through." It has been said that, as much as 85% of human cancer
is due to environmental factors. This statement is based on indirect
evidence or deductive reasoning processes which intuitively balance
evidence for the operation of genetic factors against evidence for the
operation of environmental factors.
Kilbey, B. J.
The British Experience in Environmental Mutagenesis: An Exercise in
Collaboration. MUTAT. RES., XXXIII: 73-77, 1975.
At the outset of the present expansion of interest in the study of environ-
mental mutagenesis, suggestions were made which led to the establishment
110
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of three mutation test methods as the normal means for screening new
chemicals for their mutagenicity.
There are various reasons for this change but the most important of them
are, first, that the original three test systems have on occasions proved
to be surprisingly insensitive and second, it is now clear that to pass
every compound through this screen of three tests would be prohibitively
expensive as well as extremely time-consuming.
The next and very important stage in the collaboration between those
concerned with governmental control and those concerned with testing will
come when the draft guidelines are released for discussion and comment to
industry.
Kubinski, H., N. R. Morin and P. E. Zeldin.
Increased Attachment of Nucleic Acids to Eukaryotic and Prokaryotic Cells
Induced by Chemical and Physical Carcinogens and Mutagens.
CANCER RES., XXXVI: 3025-3033, 1976. 49 refs.
Significantly enhanced attachment to Ehrlich ascites and E. coli cells was
observed for radioactive DNA and RNA in the presence of chemical
mutagens and ultimate carcinogens. In some instances, formation of
nucleic acid-protein adducts by these compounds further (or similarly)
enhanced the binding. DNA irradiated with ultraviolet light in the
presence of a protein bound more efficiently than either an unirradiated
mixture of these two macromolecules or DNA irradiated alone. The
spectrum of compounds tested and found active in this system includes
alkylating agents, aromatic amines, and carcinogenic metals. Precarcino-
gens and nonultimate carcinogenic chemicals, as well as tumor-promoting
agents, did not increase the binding. However, addition of extracts from
mouse or rat livers activated precarcinogenic and proximate carcinogenic
chemicals and resulted in enhanced cellular attachment of indicator nucleic
acids in their presence. Possible usefulness of this test system for fast
and efficient screening for environmental carcinogens and mutagens, as
well as possible relevance of the observed phenomena to in vivo effects of
chemical and physical carcinogens, is considered.
Legator, M. S.
Chemical Mutagens. ANN. REV. MED., XXIII: 413-428, 1972. 32 refs.
A review on chemical mutagens discussing:
What is a mutation?
Molecular basis for mutation
Repair and mutation process
The role of nonmammalian systems in assessing potential mutagenic
hazards to man.
Procedures recommended for evaluation of mutagenic agents
Interpretation of results
Significance of an increase in mutation rate-medical implications
Population monitoring
Correlation between carcinogenicity and mutagenicity
111
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Legator, M. S., and W. G. Flamm.
Environmental Mutagenesis and Repair. ANN. REV. BIOCHEM., XLII:
683-708, 1973. 84 refs.
A review of chemical mutagens, mutations, genetic damage and repair,
listing procedure.
Legator, M. S., and S. J. Rinkus.
The Chemical Environment and Mutagenesis, a Preprint. Division of
Environmental Toxicology and Epidemiology, University of Texas
Medical Branch, Galveston, Texas. 53 refs.
Contents:
Summary
Introduction
Chemical mutagenesis testing
combined testing
testing procedures
industrial monitoring
interpretation of results
Priority for testing
Benefit-risk analysis
Bibliography
Lieberman, M. W.
Discussion paper: Quantitative Aspects of Using DNA Repair to Detect
Mutagens and Carcinogens. ANN. N. Y. ACAD. SCI., CCLXIX:
37-42, 1975. 19 refs.
The observation that mammalian cells can repair damage to their DNA by
chemical carcinogens and mutagens has prompted much research on the
role of DNA repair mechanisms in mutagenesis and carcinpgenesis. This
communication stresses three aspects of the quantitative aspects of
detection.
Mutagenicity testing using DNA repair - mammalian cells.
Mailing, H. V.
Monitoring of Chemical Mutagens in Our Environment. ENVIRON. SCI.: AN
INTERDISCIPLINARY MONOGRAPH SERIES, 27-39. 1972. 39 refs.
A discussion of monitoring of chemical mutagens in man's environment.
Matter, B. E.
Problems of Testing Drugs for Potential Mutagenicity. MUTAT. RES.,
XXXVIII: 243-258, 1976. 71 refs.
The problem of chemically induced genetic damage has begun to alarm both
the scientific community and the general public. Mutagenicity testing, to
112
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a certain degree, is necessary for chemicals entering the environment.
As to feasiblity, although a great number of relatively simple and
practical methods are available, the evaluation of mutagenic effects at
present is an extremely complex and difficult task.
Miller, J. A.
Carcinogenesis by Chemicals: An Overview - G. H. A. Clowes Memorial
Lecture. CANCER RES., XXX: 559-576, 1970. 175 refs.
An overview of chemical carcinogenesis.
Miller, J. A., and E. C. Miller.
Chemical Carcinogenesis: Mechanisms and Approaches to Its Control. J.
NAT'L CANCER INST., XLVII: 5-14, 1971. 36 refs.
A discussion of the history, mechanisms and possible controls of chemical
carcinogenesis in man.
Mohn, G. R., and J. Ellenberger.
Genetic Effects of Cyclophosphamide, Ifosfamide and Trofosfamide. MUTAT.
RES., XXXII: 331-360, 1976.
A discussion of mutagenicity systems in reference to specific chemicals.
Montesano, R., and H. Bartsch.
Mutagenic and Carcinogenic N-nitroso Compounds: Possible Environmental
Hazards. MUTAT. RES., XXXII: 179-228, 1976. 5 refs.
A thorough discussion on mutagenicity and carcinogenicity.
Morgan, K., P. J. Hastings and R. C. von Borstel.
A Potential Hazard: Explosive Production of Mutations by Induction of
Mutators. ENVIRON. HEALTH PERSPECT., (December): 207-210,
1973.
Potentially the genetically most hazardous events that could result from
exposure to environmental mutagens are the induction of mutators. An
overall enhancement of spontaneous mutation rates would lead to the
creation of deleterious mutations which could persist almost indefinitely in
the expanding human species. The relative frequencies of induction of
antimutators and mutators are not known. Nor do we as yet fully
understand the mechanism(s) by which mutators enhance the induction of
mutations. Furthermore, the spectra of activities of spontaneous and
induced mutators need to be characterized in order to anticipate more
adequately the societal burdens which would be caused by the resulting
"explosions" of genetic damage.
113
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Narahashi, T.
In-Vitro Screening Methods Evaluating the Neurotoxic Potential of
Pesticides. Report to the U.S. Environmental Protection Agency,
Office of Research and Developmental Health Effects Research
Laboratory, Research Triangle Park, N. C., January, 1976. Research
Triangle Park, N.C.,: Environmental Protection Agency, 1976. 6 refs.
Neurotoxicity is manifested as stimulation and/or paralysis of spontaneous
discharges of the nerve cords. The techniques involved in this experi-
ment are rather simple, and require only reasonable amounts of conven-
tional electrophysiological equipment.
The order of potency of various insecticides in stimulating the crayfish
abdominal nerve cord is given.
Neel, J. V.
Evaluation of the Effects of Chemical Mutagens on Man: The Long Road
Ahead. PROC. NAT. ACAD. SCI., LXIVII: -908-915, 1970. 49 refs.
By analogy with the problem of evaluating the genetic risks of radiation, it
appears that it will be difficult to assess the mutagenicity for man of the
wide range of chemicals to which populations are exposed.
Nichols, W. W.
Somatic Mutation in Biologic Research. HEREDITAS, LXXXI: 225-236,
1975. 71 refs.
In the last few years rapid progress has been made in several labs in the
area of a possible etiologic role of somatic mutation in carcinogenesis and
aging. Studies such as metabolic activation of an initial carcinogen to its
active form, the genetic effects of tumor viruses, studies of DNA repair
mechanisms, specific chromosomal patterns observed with banding
techniques, and epidemiologic studies produce a strong probability of the
involvement of mutational events in the initiation of malignancy.
Similarly in aging, the observations that human fibroblast-like cells exhibited
a finite lifespan in culture made it apparent that this could serve as one
model to study cellular and molecular mechanisms of senescence in the
absence of many of the complexities and variables found in the intact
organism. Chromosomal mutations can be examined throughout the
lifespan of these cells. In addition, specific locus mutations can be
examined by somatic cell genetic techniques and various types of DNA
repair can be studied. In this way a profile of genetic damage can be
obtained sequentially with increasing chronologic age of these cells in an
effort to estimate the role of somatic mutation as an etiological or
modifying event of senescence in vitro.
Occupational Safety and Health Administration. Final Rules Set for
Exposure to Carcinogens. CHEM. ENGNG. NEWS, (Feb. 11): 12-13,
1974.
A description of the rules and regulations set up by the Occupational
Safety and Health Administration concerning 14 chemical carcinogens.
114
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Ong, T.-M.
Aflatoxin Mutagenesis. MUTAT. RES., XXXII: 35-53, 1975. 108 refs.
A review of mutagenesis, carcinogenesis and teratogenesis of aflatoxin.
Pellizzari, E. D.
Development of Analytical Techniques for Measuring Ambient Atmospheric
Carcinogenic Vapors. Report to the Environmental Sciences Research
Laboratory, Office of Research and Development, U. S. Environmental
Protection Agency, Research Triangle Park, N. C., November 1975.
Research Triangle Park, N. C.: Environmental Protection Agency,
1975. 51 refs.
Analytical techniques and instrumentation, developed during the previous
contract year, were perfected and evaluated for the collection and
analysis of carcinogenic and mutagenic vapors occurring ir ambient air.
The areas of investigation included (a) the performance of a sorbent
cartridge sampler for hazardous vapors occurring at concentrations of
ng/m; (b) the design, fabrication, and performance of a portable field
samples; and (c) the identification of hazardous and background
pollutants from several geographical areas in the Continental U.S.
Rail, D. P.
Difficulties in Extrapolating the Results of Toxicity Studies in Laboratory
Animals to Man. ENVIRON. RES., II: 360-367,1969. 13 refs.
Careful studies with laboratory animals usually will predict the possibility of
irreversible toxicity. There are hazards in irreversible toxicity.
Laboratory animals' are unlikely to aid in a clinically useful way in the
prediction of low-incidence toxicities. There is an urgent need for imple-
mentation of a well-devised scheme for monitoring clinical drug use in the
general population. No biological process is perfect, therefore there must
be an effective monitoring system for chemical or drug toxicity at the
clinical level.
Schoneich, J.
Safety Evaluation Based on Microbial Assay Procedures. MUTAT. RES., II:
360-367, 1969. 13 refs.
Careful studies with laboratory animals usually will predict the possibility of
irreversible toxicity. There are hazards in irreversible toxicity.
Laboratory animals are unlikely to aid in a clinically useful way in the
prediction of low-incidence toxicities. There is an urgent need for
implementation of a well-devised scheme for monitoring clinical drug use in
the general population. No biological process is perfect, therefore there
must be an effective monitoring system for chemical or drug toxicity at
the clinical level.
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Schoneich, J.
Safety Evaluation Based on Microbial Assay Procedures. MUTAT. RES.,
XLI: 89-94, 1976. 13 refs.
Microorganisms play a major role in mutation research and mutagenicity
screening for environmental chemicals. However, it should not be
forgotten that the main aim of testing is to prevent the induction of
mutations in man. It is uncommon for results obtained with bacteria to be
extrapolated to man. However, in mutagenicity testing the situation is
different. The ultimate target of chemical mutagens is DNA, which has
the same four bases and the same structure in all living systems. There
is evidence that the principal steps in the repair systems of DNA lesions
in man are likely to be the same as in bacteria.
Shafer, N., and R. W. Shafer.
Potential of Carcinogenic Effects of Hair Dyes. N. Y. ST. J. MED.,
LXXVI: 394-396, 1976. 26 refs.
Hair dyes contain many of the same compounds that are known to cause
cancer. Many chemicals can be absorbed into the body through the skin.
Experiments were conducted on laboratory animals to ascertain if
application of common commercial hair dyes can produce mammary cancer.
These tests are in progress.
Sirover, M. A., and L. A. Loeb.
Infidelity of DNA Synthesis In Vitro: Screening for Potential Metal
Mutagens or Carcinogens. SCIENCE, CXCIV: 1434-1436, 1976. 19
refs.
Thirty-one metal salts have been studied for their ability to affect the
accuracy of DNA synthesis in vitro. All ten salts of metal carcinogens
decreased the fidelity of DNA synthesis. Of the three metals which
beforehand were considered to be possible mutagens or carcinogens, only
one decreased fidelity. In contrast, 17 noncarcinogenic metal salts did
not affect fidelity even when present at concentrations that were clearly
inhibitory.
Snape, F-
Automating Pollution Measurements. AM. LAB., VIII: 51-58, 1976. 12
refs.
The importance and purpose of measuring pollution.
Sobels, F. H.
Charlotte Auerbach and Chemical Mutagenesis. MUTAT. RES., XXIX:
171-180, 1975. 63 refs.
A review of the conceptual contributions of Charlotte Auerbach to the field
of chemical mutagenesis.
116
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Stanford Research Institute.
Examples of Mutagenesis Procedures in Use at Stanford Research Institute.
Menlo Park, California: Stanford Research Institute.
Manual includes information on procedures being employed by SRI:
Microbial mutagenesis
Mammalian tissue culture and cytogenetic assays for mutagenesis
Mammalian mutagenesis (dominant lethal, translocation test)
Statistical procedure for evaluation of dominant lethal data
Sutton, H. E., and M. I. Harris
Mutagenic Effects of environmental Contaminants. ENVIRON. SCIENCES:
AN INTERDISCIPLINARY MONOGRAPH SERIES. New York: Academic
Press, 1972.
Introduction: Genetic toxicology
Gene mutation as a cause of human disease
The Molecular basis of mutation
Monitoring of chemical mutagens in our environment
The Detection of mutations with non-mammalian systems
A Bacterial system for detecting mutagens and carcinogens
The Need to detect chemically induced mutations in experimental animals
Chromosome mutations in man
The Detection of increased mutation rates in human populations
Monitoring somatic mutations in human populations
Pesticidal, industrial, food additive and drug mutagens
Mutagenicity of biologicals
Possible relationships between mutagenesis and carcinogenesis
Interrelations between carcinogenicity, mutagenicity and teratogenicity
Train, R. E.
Environmental Cancer. SCIENCE, CXCV: 443, 1977.
An editorial on environmental cancer.
Ulmer, N. S.
Physical, Chemical, and Microbiological Methods of Solid Waste Testing; Four
Additional Procedures. Report to the National Environmental Research
Center, Office of Research and Development,. U. S. Environmental
Protection Agency, Cincinnati, Ohio, March, 1974. Cincinnati, Ohio:
Environmental Protection Agency, 1974. 12 refs.
A description of four additional chemical methods used by the Solid and
Hazardous Waste Research Laboratory to analyze solid wastes and solid
waste related materials.
117
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Wagoner, J. K.
Occupational Carcinogenesis: The Two Hundred Years Since Percivall Pott.
ANN. N. Y. ACAD. SCI., CCLXXI: 1-4, 1976. 30 refs.
A summary history of occupational carcinogenesis.
Wassom, J. S.
The Literature of Chemical Mutagenesis. CHEM. MUTAGENS: PRIN.
METHODS THEIR DETECT., Ill: 271-287, 1973. A discussion of the
presentation, accumulation and sources of the literature of chemical
mutagenesis.
Wilson, J. G.
Interrelations Between Carcinogenicity, Mutagenicity, and Teratogenicity.
ENVIRON. SCI.: AN INTERDISCIPLINARY MONOGRAPH SERIES,
185-195, 1972. 20 refs.
A discussion of the three processes.
Wilson, K. W.
The Laboratory Estimation of the Biological Effects of Organic Pollutants.
PROC. R. SOC. LONDON SER. B, CLXXXIX: 459-477, 1975.
The laboratory estimation of the toxic effects of organic pollutants relies on
successive investigations of increasing sensitivity. Acute toxicity tests
are useful in providing an index of relative toxicity between compounds
but are of limited value for making ecological predictions. Many factors
can influence the assessment of acute toxicity, with chemical stability of
the test solutions and the species of test organisms employed being
perhaps the most important of these. Many sub-lethal tests are also of
limited value because the importance of the measured response for the
well-being of the animal community as a whole is not established. The
basic requirements of sub-lethal techniques are discussed, especially in
relation to compounds which may exert their toxic action through
accumulation in the tissues in the long term. The possibility of reflating
the toxicity of a compound to its chemical structure is considered.
118 * U-S- GOVERNMENT PRINTING OFFICE: 1978—740-263/1983 Region No.
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TECHNICAL REPORT DATA
(Please read Instructions on the reverse before completing)
1. REPORT NO.
EPA-600/3-78-042
2.
3. RECIPIENT'S ACCESSION-NO.
4. TITLE AND SUBTITLE
FEASIBILITY OF USING BACTERIAL STRAINS (MUTAGENESIS) TO
TEST FOR ENVIRONMENTAL CARCINOGENS
5. REPORT DATE
December 1977 issuing date
6. PERFORMING ORGANIZATION CODE
7. AUTHOR(S)
John E. Evans
8. PERFORMING ORGANIZATION REPORT NO
9. PERFORMING ORGANIZATION NAME AND ADDRESS
University of Houston
Department of Biology
Houston, TX 770^
10. PROGRAM ELEMENT NO.
1EA615
11. CONTRACT/GRANT NO.
Grant No. R-80**586
12. SPONSORING AGENCY NAME AND ADDRESS
Environmental Research Laboratory, Gulf
Office of Research and Development
U.S. Environmental Protection Agency
Gulf Breeze, FL 32561
Breeze
13. TYPE OF REPORT AND PERIOD COVERED
Final 6/15/76-5/1V77
14. SPONSORING AGENCY CODE
EPA/600/04
15. SUPPLEMENTARY NOTES
16. ABSTRACT
A rapidly growing store of data is available relative to the potential mutagen-
icity and carcingenicity of new products of chemical substances manufactured for
commerce in recent years. Literature regarding mixtures, such as chemical wastes,
however, is scarce and hard to find.
A literature review was undertaken to assess feasibility of using bacteria as
screening agents to detect environmental carcinogens. Mutagenicity data were in-
cluded in the study because growing experimental evidence indicates that most chemi-
cal carcinogens are mutagens, and many mutagens may be carcinogens.
This investigation found that bacterial mutagenesis can be used to initiate a
series of studies designed to screen for potential mutagens and carcinogens in mixed
chemical wastes.
This report was submitted in fulfillment of Grant No. R-80ii586 by the University
of Houston under partial sponsorship of the U.S. Environmental Protection Agency.
This report covers the period 15 June 1976 to ]k April 1977- Work was completed as of
1 May 1977.
17.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
b.lDENTIFIERS/OPEN ENDED TERMS C. COSATI Field/Group
Key words -
Mutagens
Carcinogens
Environmental carcinogen
Chemical Wastes
Bacterial mutagensis
06/F
18. DISTRIBUTION STATEMENT
Release to public
19. SECURITY CLASS (This Report)
unclassified
21. NO. OF PAGES
20. SECURITY CLASS (Thispage)
unclassified
22. PRICE
EPA Form 2220-1 (9-73)
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