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. 1983 Jan;47:305–317. doi: 10.1289/ehp.8347305

Comparison between carcinogenicity and mutagenicity based on chemicals evaluated in the IARC monographs.

H Bartsch, L Tomatis
PMCID: PMC1569391  PMID: 6337827

Abstract

The qualitative relationship between carcinogenicity and mutagenicity (DNA-damaging activity), based on chemicals which are known to be or suspected of being carcinogenic to man and/or to experimental animals, is analyzed using 532 chemicals evaluated in Volumes 1-25 of the IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. About 40 compounds (industrial processes) were found to be either definitely or probably carcinogenic to man, and 130 chemicals have been adequately tested in rodents and most of them also in various short-term assays. For a comparison between the carcinogenicity of a chemical and its behavior in short-term tests, systems were selected that have a value for predicting carcinogenicity. These were divided into mutagenicity in (A) the S. typhimurium/microsome assay, (B) other submammalian systems and (C) cultured mammalian cells; (D) chromosomal abnormalities in mammalian cells; (E) DNA damage and repair; (F) cell transformation (or altered growth properties) in vitro. The following conclusions can be drawn. In the absence of studies in man, long-term animal tests are still today the only ones capable of providing evidence of the carcinogenic effect of a chemical. The development and application of an appropriate combination of short-term tests (despite current limitations) can significantly contribute to the prediction/confirmation of the carcinogenic effects of chemicals in animals/man. Confidence in positive tests results is increased when they are confirmed in multiple short-term tests using nonrepetitive end points and different activation systems. Assays to detect carcinogens which do not act via electrophiles (promoters) need to be developed. The results of a given short-term test should be interpreted in the context of other toxicological data. Increasing demand for quantitative carcinogenicity data requires further examination of whether or not there is a quantitative relationship between the potency of a carcinogen in experimental animals/man, and its genotoxic activity in short-term tests. At present, such a relationship is not sufficiently established for it to be used for the prediction of the carcinogenic potency of new compounds.

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Selected References

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  1. Abe S., Sasaki M. Chromosome aberrations and sister chromatid exchanges in Chinese hamster cells exposed to various chemicals. J Natl Cancer Inst. 1977 Jun;58(6):1635–1641. doi: 10.1093/jnci/58.6.1635. [DOI] [PubMed] [Google Scholar]
  2. Bartsch H., Malaveille C., Camus A. M., Martel-Planche G., Brun G., Hautefeuille A., Sabadie N., Barbin A., Kuroki T., Drevon C. Validation and comparative studies on 180 chemicals with S. typhimurium strains and V79 Chinese hamster cells in the presence of various metabolizing systems. Mutat Res. 1980 Jul;76(1):1–50. doi: 10.1016/0165-1110(80)90002-0. [DOI] [PubMed] [Google Scholar]
  3. Bartsch H., Malaveille C., Tierney B., Grover P. L., Sims P. The association of bacterial mutagenicity of hydrocarbon-derived 'bay-region' dihydrodiols with the Iball indices for carcinogenicity and with the extents of DNA-binding on mouse skin of the parent hydrocarbons. Chem Biol Interact. 1979 Jul;26(2):185–196. doi: 10.1016/0009-2797(79)90022-x. [DOI] [PubMed] [Google Scholar]
  4. Benedict W. F., Banerjee A., Gardner A., Jones P. A. Induction of morphological transformation in mouse C3H/10T1/2 clone 8 cells and chromosomal damage in hamster A(T1)C1-3 cells by cancer chemotherapeutic agents. Cancer Res. 1977 Jul;37(7 Pt 1):2202–2208. [PubMed] [Google Scholar]
  5. Bigger C. A., Tomaszewski J. E., Dipple A. Differences between products of binding of 7,12-dimethylbenz[a]anthracene to DNA in mouse skin and in a rat liver microsomal system. Biochem Biophys Res Commun. 1978 Jan 13;80(1):229–235. doi: 10.1016/0006-291x(78)91127-0. [DOI] [PubMed] [Google Scholar]
  6. Bouck N., di Mayorca G. Somatic mutation as the basis for malignant transformation of BHK cells by chemical carcinogens. Nature. 1976 Dec 23;264(5588):722–727. doi: 10.1038/264722a0. [DOI] [PubMed] [Google Scholar]
  7. Clive D., Johnson K. O., Spector J. F., Batson A. G., Brown M. M. Validation and characterization of the L5178Y/TK+/- mouse lymphoma mutagen assay system. Mutat Res. 1979 Jan;59(1):61–108. doi: 10.1016/0027-5107(79)90195-7. [DOI] [PubMed] [Google Scholar]
  8. Coombs M. M., Dixon C., Kissonerghis A. M. Evaluation of the mutagenicity of compounds of known carcinogenicity, belonging to the benz[a]anthracene, chrysene, and cyclopenta[a]phenanthrene series, using Ames's test. Cancer Res. 1976 Dec;36(12):4525–4529. [PubMed] [Google Scholar]
  9. Cooper J. A., 2nd, Saracci R., Cole P. Describing the validity of carcinogen screening tests. Br J Cancer. 1979 Jan;39(1):87–89. doi: 10.1038/bjc.1979.10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Drevon C., Piccoli C., Montesano R. Mutagenicity assays of estrogenic hormones in mammalian cells. Mutat Res. 1981 May;89(1):83–90. doi: 10.1016/0165-1218(81)90134-8. [DOI] [PubMed] [Google Scholar]
  11. Fisher P. B., Weinstein I. B., Eisenberg D., Ginsberg H. S. Interactions between adenovirus, a tumor promoter, and chemical carcinogens in transformation of rat embryo cell cultures. Proc Natl Acad Sci U S A. 1978 May;75(5):2311–2314. doi: 10.1073/pnas.75.5.2311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Green M. H., Muriel W. J. Mutagen testing using TRP+ reversion in Escherichia coli. Mutat Res. 1976 Feb;38(1):3–32. doi: 10.1016/0165-1161(76)90076-5. [DOI] [PubMed] [Google Scholar]
  13. Huberman E., Sachs L. Cell-mediated mutagenesis of mammalian cells with chemical carcinogens. Int J Cancer. 1974 Mar 15;13(3):326–333. doi: 10.1002/ijc.2910130308. [DOI] [PubMed] [Google Scholar]
  14. Huberman E., Sachs L. Mutability of different genetic loci in mammalian cells by metabolically activated carcinogenic polycyclic hydrocarbons. Proc Natl Acad Sci U S A. 1976 Jan;73(1):188–192. doi: 10.1073/pnas.73.1.188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Krahn D. F., Heidelberger C. Liver homogenate-mediated mutagenesis in chinese hamster V79 cells by polycyclic aromatic hydrocarbons and aflatoxins. Mutat Res. 1977 Feb 1;46(1):27–44. doi: 10.1016/0165-1161(77)90108-x. [DOI] [PubMed] [Google Scholar]
  16. Kuroki T., Bartsch H. Mutagenicity of some N- and O-acyl derivatives of N-hydroxy-2-aminofluorene in V79 Chinese hamster cells. Cancer Lett. 1979 Feb;6(2):67–72. doi: 10.1016/s0304-3835(79)80002-6. [DOI] [PubMed] [Google Scholar]
  17. Kuroki T., Drevon C., Montesano R. Microsome-mediated mutagenesis in V79 Chinese hamster cells by various nitrosamines. Cancer Res. 1977 Apr;37(4):1044–1050. [PubMed] [Google Scholar]
  18. Langenbach R., Freed H. J., Raveh D., Huberman E. Cell specificity in metabolic activation of aflatoxin B1 and benzo(a)pyrene to mutagens for mammalian cells. Nature. 1978 Nov 16;276(5685):277–280. doi: 10.1038/276277a0. [DOI] [PubMed] [Google Scholar]
  19. Malaveille C., Tierney B., Grover P. L., Sims P., Bartsch H. High microsome-mediated mutagenicity of the 3,4-dihydrodiol of 7-methylbenz[a]anthracene in S. typhimurium TA 98. Biochem Biophys Res Commun. 1977 Mar 21;75(2):427–433. doi: 10.1016/0006-291x(77)91060-9. [DOI] [PubMed] [Google Scholar]
  20. Martin C. N., McDermid A. C., Garner R. C. Testing of known carcinogens and noncarcinogens for their ability to induce unscheduled DNA synthesis in HeLa cells. Cancer Res. 1978 Aug;38(8):2621–2627. [PubMed] [Google Scholar]
  21. McCann J., Choi E., Yamasaki E., Ames B. N. Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals. Proc Natl Acad Sci U S A. 1975 Dec;72(12):5135–5139. doi: 10.1073/pnas.72.12.5135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Nagao M., Sugimura T., Matsushima T. Environmental mutagens and carcinogens. Annu Rev Genet. 1978;12:117–159. doi: 10.1146/annurev.ge.12.120178.001001. [DOI] [PubMed] [Google Scholar]
  23. Nagao M., Yahagi T., Seino Y., Sugimura T., Ito N. Mutagenicities of quinoline and its derivatives. Mutat Res. 1977 Mar;42(3):335–342. doi: 10.1016/s0027-5107(77)80037-7. [DOI] [PubMed] [Google Scholar]
  24. O'Neill J. P., Couch D. B., Machanoff R., San Sebastian J. R., Brimer P. A., Hsie A. W. A quantitative assay of mutation induction at the hypoxanthine-guanine phosphoribosyl transferase locus in Chinese hamster ovary cells (CHO/HGPRT system): utilization with a variety of mutagenic agents. Mutat Res. 1977 Oct;45(1):103–109. doi: 10.1016/0027-5107(77)90048-3. [DOI] [PubMed] [Google Scholar]
  25. Ong T. M., De Serres F. J. Mutagenicity of chemical carcinogens in Neurospora crassa. Cancer Res. 1972 Sep;32(9):1890–1893. [PubMed] [Google Scholar]
  26. Parodi S., De Flora S., Cavanna M., Pino A., Robbiano L., Bennicelli C., Brambilla G. DNA-damaging activity in vivo and bacterial mutagenicity of sixteen hydrazine derivatives as related quantitatively to their carcinogenicity. Cancer Res. 1981 Apr;41(4):1469–1482. [PubMed] [Google Scholar]
  27. Perry P., Evans H. J. Cytological detection of mutagen-carcinogen exposure by sister chromatid exchange. Nature. 1975 Nov 13;258(5531):121–125. doi: 10.1038/258121a0. [DOI] [PubMed] [Google Scholar]
  28. Petzold G. L., Swenberg J. A. Detection of DNA damage induced in vivo following exposure of rats to carcinogens. Cancer Res. 1978 Jun;38(6):1589–1594. [PubMed] [Google Scholar]
  29. Purchase I. F., Longstaff E., Ashby J., Styles J. A., Anderson D., Lefevre P. A., Westwood F. R. An evaluation of 6 short-term tests for detecting organic chemical carcinogens. Br J Cancer. 1978 Jun;37(6):873–903. doi: 10.1038/bjc.1978.132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Reznikoff C. A., Bertram J. S., Brankow D. W., Heidelberger C. Quantitative and qualitative studies of chemical transformation of cloned C3H mouse embryo cells sensitive to postconfluence inhibition of cell division. Cancer Res. 1973 Dec;33(12):3239–3249. [PubMed] [Google Scholar]
  31. Rosenkranz H. S., Poirier L. A. Evaluation of the mutagenicity and DNA-modifying activity of carcinogens and noncarcinogens in microbial systems. J Natl Cancer Inst. 1979 Apr;62(4):873–892. [PubMed] [Google Scholar]
  32. San R. H., Stich H. F. DNA repair synthesis of cultured human cells as a rapid bioassay for chemical carcinogens. Int J Cancer. 1975 Aug 15;16(2):284–291. doi: 10.1002/ijc.2910160211. [DOI] [PubMed] [Google Scholar]
  33. San R. H., Williams G. M. Rat hepatocyte primary cell culture-mediated mutagenesis of adult rat liver epithelial cells by procarcinogens. Proc Soc Exp Biol Med. 1977 Dec;156(3):534–538. doi: 10.3181/00379727-156-39974. [DOI] [PubMed] [Google Scholar]
  34. Selkirk J. K. Divergence of metabolic activation systems for short-term mutagenesis assays. Nature. 1977 Dec 15;270(5638):604–607. doi: 10.1038/270604a0. [DOI] [PubMed] [Google Scholar]
  35. Sirover M. A., Loeb L. A. Infidelity of DNA synthesis in vitro: screening for potential metal mutagens or carcinogens. Science. 1976 Dec 24;194(4272):1434–1436. doi: 10.1126/science.1006310. [DOI] [PubMed] [Google Scholar]
  36. Swenberg J. A., Petzold G. L., Harbach P. R. In vitro DNA damage/alkaline elution assay for predicting carcinogenic potential. Biochem Biophys Res Commun. 1976 Sep 20;72(2):732–738. doi: 10.1016/s0006-291x(76)80100-3. [DOI] [PubMed] [Google Scholar]
  37. Tomatis L., Agthe C., Bartsch H., Huff J., Montesano R., Saracci R., Walker E., Wilbourn J. Evaluation of the carcinogenicity of chemicals: a review of the Monograph Program of the International Agency for Research on Cancer (1971 to 1977). Cancer Res. 1978 Apr;38(4):877–885. [PubMed] [Google Scholar]
  38. Weeks C. E., Allaben W. T., Tresp N. M., Louie S. C., Lazear E. J., King C. M. Effects of structure of N-acyl-N-2-fluorenylhydroxylamines on arylhydroxamic acid acyltransferase, sulfotransferase, and deacylase activities, and on mutations in Salmonella typhimurium TA 1538. Cancer Res. 1980 Apr;40(4):1204–1211. [PubMed] [Google Scholar]
  39. Williams G. M. Detection of chemical carcinogens by unscheduled DNA synthesis in rat liver primary cell cultures. Cancer Res. 1977 Jun;37(6):1845–1851. [PubMed] [Google Scholar]
  40. Wislocki P. G., Gadek K. M., Chou M. W., Yang S. K., Lu A. Y. Carcinogenicity and mutagenicity of the 3,4-dihydrodiols and other metabolites of 7,12-dimethylbenz(a)anthracene and its hydroxymethyl derivatives. Cancer Res. 1980 Oct;40(10):3661–3664. [PubMed] [Google Scholar]
  41. Wolff S. Sister chromatid exchange. Annu Rev Genet. 1977;11:183–201. doi: 10.1146/annurev.ge.11.120177.001151. [DOI] [PubMed] [Google Scholar]
  42. Zimmermann F. K. Procedures used in the induction of mitotic recombination and mutation in the yeast Saccharomyces cerevisiae. Mutat Res. 1975 Apr;31(2):71–86. doi: 10.1016/0165-1161(75)90069-2. [DOI] [PubMed] [Google Scholar]

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