Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals.

Abstract

About 300 carcinogens and non-carcinogens of a wide variety of chemical types have been tested for mu- There is considerable evidence that a large proportion of human cancer may be caused by exposure to toxic chemicals in the environment, very few of which have been tested for carcinogenicity or mutagenicity. A program of cancer prevention aimed at identifying and eliminating human exposure to hazardous chemicals requires the development of rapid, inexpensive, screening methods as complements to expensive, long-term animal tests, to pinpoint dangerous chemicals among the thousands to which humans are exposed. The Salmonella/microsome mutagenicity test (1-4) has been sufficiently developed and validated to be seriously considered for widespread use in this way. The considerable evidence (5), much of it obtained using this test (1)(2)(3)(4)(6)(7)(8)(9)(10)(11)(12)(13), that with few exceptions carcinogens are mutagens, supports the desirability of using this type of rapid and economical test system as a screening technique (1-3).Chemicals are tested for mutagenicity on petri plates with several specially constructed mutants of Salmonella typhimurium (2-4). Homogenates of rat (or human) liver, (S-9 Mix), are added directly to the petri plates, thus incorporating an important aspect of mammalian metabolism into the in vitro test (2). In this way, a wide variety of carcinogens requiring metabolic activation can be detected easily as mutagens (2, 4, 5). The system has been recently reviewed (6) and the test method described in detail (7).The present paper presents mutagenicity data on a large number of carcinogens and non-carcinogens of many different classes that have been examined in the system using a standard methodology (7) All non-mutagens, and most mutagens, have been tested, using the recently improved standard methodology (7), on the new R factor tester strains (4) as well as the earlier standard tester strains (3). Non-mutagens have been tested over a wide dose range both with and without the liver microsome activating system.In addition to our previously published studies and new work presented here, results have been contributed to this compilation by a number of laboratories using this test, including a large contribution from Japan. Some of the chemicals tested are also specified in a contract sponsored by the National Cancer Institute (V. Simmon and H. Rosenkranz, to be published). Some of the non-carcinogens we tested were specified in a contract sponsored by the Environmental Protection Agency to B. Commoner.We have not reported on any metal carcinogens, though three or four that have been tested are negative in the standard test. The test system is not suitable for metals entering the bacteria because of the large amount of Mg salts, citrate, and phosphate in the minimal medium. A number of carcinogenic metals have been shown to be mutagens in bacteria by means of a different methodology, e.g. ref.14.In addition to the compounds presented we have tested 46 common biochemicals that are non-ca...

The in vitro genotoxicity of benzoic acid in human peripheral blood lymphocytes

“…Benzoic acid was tested as negative in several Ames tests and in one DNA damage assay with different Salmonella typhimurium strains in the presence or absence of metabolic activation (McCann et al 1975;Nakamura et al 1987;Ishidate et al 1984;Zeiger et al 1988). Only in one recombination assay with Bacillus subtilis H17 and M45 was a positive result obtained (Nonaka 1989).…”

A new theory of carcinogenesis

“…A WIDE VARIETY of carcinogens has been shown to be mutagenic, especially in the test system developed by Ames and his collaborators (Ames et al, 1973;McCann et al, 1975;McCann & Ames, 1976). For this and other reasons a convincing case can be made for the theory that the phenotype of the malignant cell is the consequence of one or more heritable gene or chromosome mutations (for a review see Cairns, 1978).…”

Effects of repeated applications of two semi-permanent hair dyes to the skin of A and DBAf mice

“…Tests of some 300 carcinogens and non-carcinogens in the bacterial system showed a wide measure of qualitative agreement between mutagenic and carcinogenic activities (McCann et al, 1975; McCann and Ames 1 976) while in an important comparative study of 6 shortterm tests for carcinogen detection (Purchase et al, 1976) tests for bacterial mutagenicity and for cell transformation in vitro showed the most consistent correlations with the presence or absence of carcinogenic activity.…”

“…There is consequently great current interest in various short-term assays that, though not capable of proving the carcinogenicity of a compound, may be valuable as screening tests. Of the battery of tests considered necessary for adequate prescreening, at present the most useful appear to be those which detect chemically-induced reversion to prototropy in amino-acid-requiring mutants of Salmonella typhimurium and Escherichia coli. These test have been developed particularly by Ames and his colleagues, who have reported the results of testing some 300 carcinogenic and non-carcinogenic compounds (McCann et al, 1975;McCann and Ames, 1976).…”