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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...

We described previously a simple test on petri plates for detecting chemical carcinogens as mutagens, using an especially sensitive set of bacterial strains to detect m4tagenic activity and a mammalian liver extract for carcinogen activation. We now extend the utility of the method by introducing two new bacterial strains which can detect with great sensitivity many carcinogens which we did not detect before or detected with less sensitivity. Among these carcinogens are aflatoxin B1, sterigmatocystin, benzyl chloride, benzojajpyrene, 7,12-dimethylbenzanthracene, F'-acetoxysafrole, and the nitrofuran food additive furylfuramide (AF-2).The new strains TA100 and TA98 contain an R factor plasmid, pKM101, in our standard tOeter strains TA1535 and TA1538. The R factor increases mutagenesis with certain mutagens, but not others. We present evidence that the mutagens that become more effective work through an error-prone recombinational repair.We have previously described a very sensitive and simple bacterial test for detecting chemical mutagens (1-4). The compounds are tested on petri plates with specially constructed mutants of Salmonella typhimurium as tester strains. Four tester strains have been selected, after screening hundreds of mutants, for sensitivity and specificity in being reverted from a histidine requirement back to prototrophy by a variety of mutagens. One strain (TA1535) can be used to detect mutagens causing base-pair substitutions and three (TA1536, TA1537, and TA1538) to detect various kinds of frameshift mutagens. In addition to the histidine mutation, we have added to the tester strains two additional mutations that greatly increase their sensitivity to mutagens: one causes loss of the excision repair system and the other loss of the lipopolysaccharide barrier that coats the surface of the bacteria (3).We have shown that by adding a microsomal activation system from rat (or human) liver to the petri plates, a wide variety of carcinogens can be activated to mutagens and detected easily. Thus, an important aspect of mammalian metabolism can be duplicated in an in vitro test. A large group of carcinogens-aflatoxin B1, benzo[a]pyrene, 2-acetylaminofluorene, etc., have been detected as reactive frameshift mutagens after liver activation (4). Each activated molecule contains a ring system capable of stacking interaction with DNA and an electrophilic group that can react with DNA (5-8).Other groups of carcinogens have been detected as mutagens causing base-pair substitutions: fl-propiolactone, propanesultone, etc. (1-4). Some carcinogens, such as nitroquinoline-1-oxide (NQNO), cause both types of mutations (3).We report here the development of two new bacterial strains which contain an R factor (plasmids carrying antibiotic resistance genes) and which greatly extend the usefulness of the test system. This work stemmed from the observation of MacPhee (9) that methyl methanesulfonate (MMS) and trimethyl phosphate werei more effective in reverting his646 (the histidine mutation in TA1535) when anoth...

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