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. 1975 Dec;72(12):5135–5139. doi: 10.1073/pnas.72.12.5135

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

J McCann, E Choi, E Yamasaki, B N Ames
PMCID: PMC388891  PMID: 1061098

Abstract

About 300 carcinogens and non-carcinogens of a wide variety of chemical types have been tested for mutagenicity in the simple Salmonella/microsome 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: potency varies over a 10(6)-fold range. There is a high correlation between carcinogenicity and mutagenicity: 90% (156/174) of carcinogens are mutagenic in the test and despite the severe limitations inherent in defining non-carcinogenicity, few "non-carcinogens" show any degree of mutagenicity. The results also demonstrate the great utility, and define the limitations, of the test in detecting environmental carcinogens.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ames B. N., Durston W. E., Yamasaki E., Lee F. D. Carcinogens are mutagens: a simple test system combining liver homogenates for activation and bacteria for detection. Proc Natl Acad Sci U S A. 1973 Aug;70(8):2281–2285. doi: 10.1073/pnas.70.8.2281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ames B. N., Gurney E. G., Miller J. A., Bartsch H. Carcinogens as frameshift mutagens: metabolites and derivatives of 2-acetylaminofluorene and other aromatic amine carcinogens. Proc Natl Acad Sci U S A. 1972 Nov;69(11):3128–3132. doi: 10.1073/pnas.69.11.3128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ames B. N., Kammen H. O., Yamasaki E. Hair dyes are mutagenic: identification of a variety of mutagenic ingredients. Proc Natl Acad Sci U S A. 1975 Jun;72(6):2423–2427. doi: 10.1073/pnas.72.6.2423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ames B. N., Lee F. D., Durston W. E. An improved bacterial test system for the detection and classification of mutagens and carcinogens. Proc Natl Acad Sci U S A. 1973 Mar;70(3):782–786. doi: 10.1073/pnas.70.3.782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ames B. N., Sims P., Grover P. L. Epoxides of carcinogenic polycyclic hydrocarbons are frameshift mutagens. Science. 1972 Apr 7;176(4030):47–49. doi: 10.1126/science.176.4030.47. [DOI] [PubMed] [Google Scholar]
  6. Bartsch H., Malaveille C., Montesano R. Human, rat and mouse liver-mediated mutagenicity of vinyl chloride in S. typhimurium strains. Int J Cancer. 1975 Mar 15;15(3):429–437. doi: 10.1002/ijc.2910150309. [DOI] [PubMed] [Google Scholar]
  7. Bartsch H., Malaveille C., Montesano R. In vitro metabolism and microsome-mediated mutagenicity of dialkylnitrosamines in rat, hamster, and mouse tissues. Cancer Res. 1975 Mar;35(3):644–651. [PubMed] [Google Scholar]
  8. Bartsch H., Malaveille C., Montesano R., Tomatis L. Tissue-mediated mutagenicity of vinylidene chloride and 2-chlorobutadiene in Salmonella typhimurium. Nature. 1975 Jun 19;255(5510):641–643. doi: 10.1038/255641a0. [DOI] [PubMed] [Google Scholar]
  9. Borchert P., Miller J. A., Miller E. C., Shires T. K. 1'-Hydroxysafrole, a proximate carcinogenic metabolite of safrole in the rat and mouse. Cancer Res. 1973 Mar;33(3):590–600. [PubMed] [Google Scholar]
  10. Coombs M. M., Bhatt T. S., Croft C. J. Correlation between carcinogenicity and chemical structure in cyclopenta(a)phenanthrenes. Cancer Res. 1973 Apr;33(4):832–837. [PubMed] [Google Scholar]
  11. Durston W. E., Ames B. N. A simple method for the detection of mutagens in urine: studies with the carcinogen 2-acetylaminofluorene. Proc Natl Acad Sci U S A. 1974 Mar;71(3):737–741. doi: 10.1073/pnas.71.3.737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gabridge M. G., Denunzio A., Legator M. S. Microbial mutagenicity of streptozotocin in animal-mediated assays. Nature. 1969 Jan 4;221(5175):68–70. doi: 10.1038/221068a0. [DOI] [PubMed] [Google Scholar]
  13. Grover P. L., Sims P., Mitchley B. C., Roe F. J. The carcinogenicity of polycyclic hydrocarbon epoxides in newborn mice. Br J Cancer. 1975 Feb;31(2):182–188. doi: 10.1038/bjc.1975.24. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Haese W. H., Smith D. L., Bueding E. Hycanthone-induced hepatic changes in mice infected with Schistosoma mansoni. J Pharmacol Exp Ther. 1973 Sep;186(3):430–440. [PubMed] [Google Scholar]
  15. Hartman P. E., Levine K., Hartman Z., Berger H. Hycanthone: a frameshift mutagen. Science. 1971 Jun 4;172(3987):1058–1060. doi: 10.1126/science.172.3987.1058. [DOI] [PubMed] [Google Scholar]
  16. Kada T., Moriya M., Shirasu Y. Screening of pesticides for DNA interactions by "rec-assay" and mutagenesis testing, and frameshift mutagens detected. Mutat Res. 1974 Aug;26(4):243–248. doi: 10.1016/s0027-5107(74)80021-7. [DOI] [PubMed] [Google Scholar]
  17. Kier L. D., Yamasaki E., Ames B. N. Detection of mutagenic activity in cigarette smoke condensates. Proc Natl Acad Sci U S A. 1974 Oct;71(10):4159–4163. doi: 10.1073/pnas.71.10.4159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lambelin G., Roba J., Roncucci R., Parmentier R. Carcinogenicity of 6-aminochrysene in mice. Eur J Cancer. 1975 May;11(5):327–334. doi: 10.1016/0014-2964(75)90060-2. [DOI] [PubMed] [Google Scholar]
  19. Legator M. S., Connor T. H., Stoeckel M. Detection of mutagenic activity of metronidazole and niridazole in body fluids of humans and mice. Science. 1975 Jun 13;188(4193):1118–1119. doi: 10.1126/science.766186. [DOI] [PubMed] [Google Scholar]
  20. Longnecker D. S., Curphey T. J. Adenocarcinoma of the pancreas in azaserine-treated rats. Cancer Res. 1975 Aug;35(8):2249–2258. [PubMed] [Google Scholar]
  21. MATTHEWS C., DAVIDSON J., BAUER E., MORRISON J. L., RICHARDSON A. P. P-Hydroxybenzoic acid esters as preservatives. II. Acute and chronic toxicity in dogs, rats, and mice. J Am Pharm Assoc Am Pharm Assoc. 1956 Apr;45(4):260–267. doi: 10.1002/jps.3030450420. [DOI] [PubMed] [Google Scholar]
  22. Magee P. N., Barnes J. M. Carcinogenic nitroso compounds. Adv Cancer Res. 1967;10:163–246. doi: 10.1016/s0065-230x(08)60079-2. [DOI] [PubMed] [Google Scholar]
  23. Malling H. V. Dimethylnitrosamine: formation of mutagenic compounds by interaction with mouse liver microsomes. Mutat Res. 1971 Dec;13(4):425–429. doi: 10.1016/0027-5107(71)90054-6. [DOI] [PubMed] [Google Scholar]
  24. Malling H. V., Frantz C. N. In vitro versus in vivo metabolic activation of mutagens. Environ Health Perspect. 1973 Dec;6:71–82. doi: 10.1289/ehp.730671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. McCann J., Simmon V., Streitwieser D., Ames B. N. Mutagenicity of chloroacetaldehyde, a possible metabolic product of 1,2-dichloroethane (ethylene dichloride), chloroethanol (ethylene chlorohydrin), vinyl chloride, and cyclophosphamide. Proc Natl Acad Sci U S A. 1975 Aug;72(8):3190–3193. doi: 10.1073/pnas.72.8.3190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Monti-Bragadin C., Tamaro M., Banfi E. Mutagenic activity of diazoacetylglycine derivatives. Antimicrob Agents Chemother. 1974 Nov;6(5):655–656. doi: 10.1128/aac.6.5.655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Nishioka H. Mutagenic activities of metal compounds in bacteria. Mutat Res. 1975 Jun;31(3):185–189. doi: 10.1016/0165-1161(75)90088-6. [DOI] [PubMed] [Google Scholar]
  28. Reddy B. S., Narisawa T., Wright P., Vukusich D., Weisburger J. H., Wynder E. L. Colon carcinogenesis with azoxymethane and dimethylhydrazine in germ-free rats. Cancer Res. 1975 Feb;35(2):287–290. [PubMed] [Google Scholar]
  29. Smith D. W. Mutagenicity of cycasin aglycone (methylazoxymethanol), a naturally occurring carcinogen. Science. 1966 May 27;152(3726):1273–1274. doi: 10.1126/science.152.3726.1273. [DOI] [PubMed] [Google Scholar]
  30. Stoner G. D., Shimkin M. B., Kniazeff A. J., Weisburger J. H., Weisburger E. K., Gori G. B. Test for carcinogenicity of food additives and chemotherapeutic agents by the pulmonary tumor response in strain A mice. Cancer Res. 1973 Dec;33(12):3069–3085. [PubMed] [Google Scholar]
  31. Takemura N., Hashida C., Terasawa M. Carcinogenic action of 5-nitroacenaphthene. Br J Cancer. 1974 Nov;30(5):481–483. doi: 10.1038/bjc.1974.225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Teranishi K., Hamada K., Watanabe H. Quantitative relationship between carcinogenicity and mutagenicity of polyaromatic hydrocarbons in Salmonella typhimurium mutants. Mutat Res. 1975 Apr;31(2):97–102. doi: 10.1016/0165-1161(75)90071-0. [DOI] [PubMed] [Google Scholar]
  33. Thiede T., Christensen B. C. Bladder tumours induced by chlornaphazine. A five-year follow-up study of chlornaphazine-treated patients with polycythaemia. Acta Med Scand. 1969 Jan-Feb;185(1-2):133–137. [PubMed] [Google Scholar]
  34. Ulland B., Finkelstein M., Weisburger E. K., Rice J. M., Weisburger J. H. Carcinogenicity of industrial chemicals propylene imine and propane sultone. Nature. 1971 Apr 16;230(5294):460–461. doi: 10.1038/230460a0. [DOI] [PubMed] [Google Scholar]
  35. Van Duuren B. L., Goldschmidt B. M., Katz C., Seidman I., Paul J. S. Carcinogenic activity of alkylating agents. J Natl Cancer Inst. 1974 Sep;53(3):695–700. doi: 10.1093/jnci/53.3.695. [DOI] [PubMed] [Google Scholar]
  36. Voogd C. E., Van der Stel J. J., Jacobs J. J. The mutagenic action of nitroimidazoles. I. Metronidazole, nimorazole, dimetridazole and ronidazole. Mutat Res. 1974 Dec;26(6):483–490. doi: 10.1016/s0027-5107(74)80049-7. [DOI] [PubMed] [Google Scholar]
  37. Weisburger J. H., Griswold D. P., Prejean J. D., Casey A. E., Wood H. B., Weisburger E. K. The carcinogenic properties of some of the principal drugs used in clinical cancer chemotherapy. Recent Results Cancer Res. 1975;(52):1–17. doi: 10.1007/978-3-642-80940-8_1. [DOI] [PubMed] [Google Scholar]
  38. Yahagi T., Nagao M., Hara K., Matsushima T., Sugimura T., Bryan G. T. Relationships 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. 1974 Sep;34(9):2266–2273. [PubMed] [Google Scholar]
  39. Yamamoto R. S., Weisburger E. K., Korzis J. Chronic administration of hydroxylamine and derivatives in mice. Proc Soc Exp Biol Med. 1967 Apr;124(4):1217–1220. doi: 10.3181/00379727-124-31969. [DOI] [PubMed] [Google Scholar]

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