The Activation of Carcinogens by Mammary Cells: Inter-Organ and Intra-Organ Specificity

  • Michael N. Gould
Part of the Basic Life Sciences book series


Evidence has been presented by epidemiologists that the etiology of the majority of human cancers has environmental factors. It is currently felt that the major environmental factor for cancers other than that of the skin is chemical (1). With the exception of alkylating and acylating agents, almost all chemical carcinogens must be metabolically activated (i.e., converted to an ultimate carcinogen) to initiate neoplasia or induce mutations (1). This activation process is important not only in vivo but is crucial for in vitro systems that are employed to study the mechanisms of carcinogenesis and to screen for environmental chemical carcinogens. Most in vitro models use either various cell homogenate fractions or intact cultured cells to metabolically activate the chemical to be evaluated. For example, Ames and his collaborators (2) use an S9 fraction of liver homogenate to metabolically activate carcinogens; the metabolic derivatives are then assayed for their ability to induce bacterial mutations. Similar systems have been used that employ specific locus mutations in mammalian cells (3,4). In other models, carcinogens are activated by cultured intact mammalian cells. The activity of the metabolized carcinogen is assayed by specific locus mutation or transformation in the activating cell itself (5), or in other co-cultivated cells that have lost their ability to activate carcinogens (6). The validity of using mutagenesis as an endpoint to identify active carcinogens has been reviewed extensively (7).


Chemical Carcinogen Mutagenesis Assay Ultimate Carcinogen Mammary Culture Specific Locus Mutation 
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  1. 1.
    Miller, E.C. 1978. Some current perspectives on chemical carcinogenesis in humans and experimental animals: Presidential address. Cancer Res. 38: 1479–1496.Google Scholar
  2. 2.
    Ames, B.N., J. McCann, and E. Yamasaki. 1975. Methods for detecting carcinogens and mutagens with the Salmonella mammalian microsome mutagenicity test. Mutat. Res. 31: 347–364.Google Scholar
  3. 3.
    Kuroki, T., C. Drevon, and R. Montesano. 1977. Microsomemediated mutagenesis of V79 Chinese hamster cells by various nitrosamines. Cancer Res. 37: 1044–1050.PubMedGoogle Scholar
  4. 4.
    Krahn, D.F., and C. Heidelberger. 1977. Liver homogenate-mediated mutagenesis in Chinese hamster V79 cells by polycyclic aromatic hydrocarcons and aflatoxins. Mutat. Res. 46: 27–44.Google Scholar
  5. 5.
    Barrett, C., and P.O.P. Ts’0. 1978. Relationship between somatic mutation and neoplastic transformation. Proc. Nat. Acad. Sci 75: 3297–3301.Google Scholar
  6. 6.
    Huberman, E., and C. Sachs. 1974. Cell-mediated mutagenesis of mammalian cells with chemical carcinogen. Int. J. Cancer 13: 326–333.Google Scholar
  7. 7.
    Meselson, M., and K. Russell. 1977. Comparisons of carcinogenic and mutagenic potency. In: Origins of Human Cancer, Volume C. H.H. Hiatt, J.D. Watsorund, J.A. Wingten, eds. Cold Spring Harbor Laboratory: Cold Spring Harbor, NY pp. 1473–1481.Google Scholar
  8. 8.
    Selkirk, J.K. 1977. Divergence of metabolic activation systems for short-term mutagenesis assays. Nature 270: 604–607.PubMedCrossRefGoogle Scholar
  9. 9.
    Bigger, C.A.H., J.E. Tomaszewski, and A. Dipple. 1978. Differences between products of 7,12-dimethylbenz[a]anthracene to DNA in mouse skin and in a rat liver microsomal system. Biochem. Biophys. Res. Comm. 80: 229–235.Google Scholar
  10. 10.
    Schmeltz, I., J. Tosk, and G.M. Williams. 1978. Comparisons of the metabolic profiles of benzo[a]pyrene obtained from primary cell culture and subcellular fractions derived from normal and methylcholanthrene-induced rat liver. Cancer Lett. 5: 81–89.PubMedCrossRefGoogle Scholar
  11. 11.
    Langenbach, R., H.J. Freed, D. Raveh, and E. Huberman. 1978. Cell specificity in metabolic activation of aflatoxin B1 and benzo[a]pyrene to mutagens for mammalian cells. Nature 276: 277–280.PubMedCrossRefGoogle Scholar
  12. 12.
    Gould, M.N. 1980. Mammary gland cell-mediated mutagenesis of mammalian cells by organ-specific carcinogens. Cancer Res. 40: 1836–1841.PubMedGoogle Scholar
  13. 13.
    Michalopoulos, G., and H.C. Pitot. 1975. Primary culture of parenchymal liver cells on collagen membranes: Morphological and biochemical observations. Exp. Cell Res. 94: 70–78.Google Scholar
  14. 14.
    Michalopoulos, G., G.L. Sattier, and H.C. Pitot. 1976. Maintenance of microsomal cytochrome b5 and P-450 in primary cultures of parenchymal liver cells on collagen membranes. Life Sci. 18: 1139–1144.PubMedCrossRefGoogle Scholar
  15. 15.
    Berwald, Y., and C. Sachs. 1965. In vitro transformation of normal cells to tumor cells by carcinogenic hydrocarbons. J. Natl. Cancer Inst. 35: 641–661.Google Scholar
  16. 16.
    Reznikoff, C.A., D.N. Brankow, and C. Heidelberger. 1973. Quantitative and qualitative studies of chemical transformation of cloned C3 mouse embryo cells sensitive to post-confluence inhibition of cell division. Cancer Res. 33: 3231–3238.PubMedGoogle Scholar
  17. 17.
    San, R.H.C., and G.M. Williams. 1977. Rat hepatocyte primary cell culture-mediated mutagenesis of adult rat liver epithelial cells by procarcinogens. Proc. Soc. Exp. Biol. Med. 156: 534–538.Google Scholar
  18. 18.
    Langenbach, R., H.J. Freed, and E. Huberman. 1978. Liver cell-mediated mutagenesis of mammalian cells by liver carcinogens. Proc. Natl. Acad. Sci. 75: 2864–2867.Google Scholar
  19. 19.
    Tompa, A., and R. Langenbach. 1979. Culture of adult rat lung cells: Benzo[a]pyrene metabolism and mutagenesis. In Vitro 15: 569–578.Google Scholar
  20. 20.
    American Cancer Society. 1979. Cancer facts and figures 1980. American Cancer Society: New York. 8 pp.Google Scholar
  21. 21.
    Gould, M.N., W.F. Biel, and K.H. Clifton. 1977. Morphological and quantitative studies of gland formation from inocula of monodispersed cells. Exp. Cell Res. 107: 405–416.Google Scholar
  22. 22.
    Gould, M.N. (MS). Chemical carcinogen activation in the rat mammary gland; intra-organ cell specificity.Google Scholar
  23. 23.
    Gould, M.N., and K.H. Clifton. 1979. Evidence for a unique in situ component of the repair of radiation damage. Radiat. Res. 77: 149–155.Google Scholar
  24. 24.
    Mulcahy, R.T., M.N. Gould, and K.H. Clifton. 1980. The survival of thyroid cells: In vivo irradiation and in situ repair. Radiat. Res. 84: 523–528.Google Scholar
  25. 25.
    Jirtle, R.L., G. Michalopoulos, J.R. McClain, and J. Crowley. (in press). The survival of parenchymal hepatocytes exposed to ionizing radiation. Cancer Res.Google Scholar
  26. 26.
    Thomas, F., and M.N. Gould. (MS). Evidence for the repair of potentially lethal damage in irradiated bone marrow.Google Scholar
  27. 27.
    United Nations Scientific Committee on the Effects of Atomic Radiation. 1977. Sources and Effects of Ionizing Radiation. United Nations: New York.Google Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • Michael N. Gould
    • 1
  1. 1.Department of Human Oncology, Wisconsin Clinical Cancer CenterUniversity of WisconsinMadisonUSA

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