Advertisement

Cell-Mediated Mutagenesis, an Approach to Studying Organ Specificity of Chemical Carcinogens

  • Robert Langenbach
  • Stephen Nesnow
Part of the Basic Life Sciences book series

Abstract

We have been interested in developing in vitro systems in which the organ and species specificity of chemical carcinogens can be studied (1–6). The phenomena of species, organ, sex, and age specificity in response to chemical carcinogens pose an intriguing problem and may be important for the extrapolation of in vivo and in vitro carcinogenesis data to humans. Many carcinogens exist in the environment in nonreactive form and must be metabolically activated to manifest their biological activity (7,8).

Keywords

High Pressure Liquid Chromatography Mutagenic Activity Chemical Carcinogen Polynuclear Aromatic Hydrocarbon Mutagenic Response 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Langenbach, R., S. Nesnow, L. Malick, R. Gingell, A. Tompa, C. Kuszynski, S. Leavitt, K. Sasseville, B. Hyatt, C. Cudak, and L. Montgomery. 1981. Organ specific activation of carcinogenic polynuclear aromatic hydrocarbons in cell culture. In: Chemical Analysis and Biological Fate: Polynuclear Aromatic Hydrocarbons. M. Cooke and A.J. Dennis, eds. Battelle Press: Columbus, OH. pp. 75–84.Google Scholar
  2. 2.
    Langenbach, R., S. Nesnow, A. Tompa, R. Gingell, and C. Kuszynski. 1981. Lung and liver cell-mediated mutagenesis systems: specificities in the activation of chemical carcinogens. Carcinogenesis 2: 851–858.PubMedCrossRefGoogle Scholar
  3. 3.
    Langenbach, R., H.J. Freed, and E. Huberman. 1978. Liver cell-mediated mutagenesis of mammalian cells by liver carcinogens. Proc. Natl. Acad. Sci. USA 75: 2864–2867.PubMedCrossRefGoogle Scholar
  4. 4.
    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
  5. 5.
    Tompa, A., and R. Langenbach. 1979. Culture of adult rat lung cells: Benzo[a]pyrene metabolism and mutagenesis. In Vitro 15: 569–578.PubMedGoogle Scholar
  6. 6.
    Langenbach, R., L. Malick, and S. Nesnow. 1981. Bladder cell-mediated mutagenesis. J. Natl. Cancer Inst. 66: 913–917.PubMedGoogle Scholar
  7. 7.
    Miller, J.A. 1970. Carcinogenesis by chemicals: an overview. Cancer Res. 30: 559–576.PubMedGoogle Scholar
  8. 8.
    Heidelberger, C. 1975. Chemical carcinogenesis. Ann. Rev. Biochem. 44: 79–121.PubMedCrossRefGoogle Scholar
  9. 9.
    Hutton, J.J., J. Meier, and C. Hackney. 1979. Comparison of the in vitro mutagenicity and metabolism of dimethylnitrosamine and benzo[a]pyrene in tissues from inbred mice treated with phenobarbital, 3-methylcholanthrene or polychlorinated biphenyls. Mutat. Res. 66: 75–94.PubMedCrossRefGoogle Scholar
  10. 10.
    Prough, R.A., V.W. Patrizi, R.T. Okita, B.S.S. Masters, and S.W. Jakobsson. 1979. Characteristics of benzo[a]pyrene metabolism by kidney, liver, and lung microsomal fractions from rodents and humans. Cancer Res. 39: 1199–1206.Google Scholar
  11. 11.
    Juchau, M.R., J. DiGiovanni, M.J. Namkung, and A.H. Jones. 1979. A comparison of the capacity of fetal and adult liver, lung, and brain to convert polycyclic aromatic hydrocarbons to mutagenic and cytotoxic metabolites in mice and rats. Toxicol. Appl. Pharmacol. 49: 171–178.PubMedCrossRefGoogle Scholar
  12. 12.
    Hundley, S.G., and R.I. Freudenthal. 1979. A comparison of benzo[a]pyrene metabolism by liver and lung microsomal enzymes from 3-methylcholanthrene-treated Rhesus monkeys and rats. Cancer Res. 37: 3120–3125.Google Scholar
  13. 13.
    Bartsch, H., E. Malaveille, and R. Montesano. 1975. In vitrometabolism and microsome-mediated mutagenicity of dialkylnitrosamines in rat, hmaster, and mouse tissues. Cancer Res. 35:644–651.PubMedGoogle Scholar
  14. 14.
    Autrup, H., F.C. Wefald, A.M. Jeffrey, H. Tate, R.D. Schwartz, B.F. Strump, and C.C. Harris. 1980. Metabolism of benzo[a]pyrene by cultured tracheobronchial tissues from mice, rats, hamsters, bovines and humans. Int. J. Cancer 25: 293–300.PubMedCrossRefGoogle Scholar
  15. 15.
    Boroujerdi, M., H. Kung, A.G.E. Wilson, and M.W. Anderson. 1981. Metabolism and DNA binding of benzo[a]pyrene in vivo in the rat. Cancer Res. 41: 951–957.PubMedGoogle Scholar
  16. 16.
    NewUnderline. R.F., C.B. Wigley, M.H. Thompson, and P. Brookes. 1977. Cell-mediated mutagenesis in cultured Chinese hamster cells by carcinogenic polycyclic hydrocarbons: nature and extent of the associated hydrocarbon-DNA reaction. Mutat. Res. 43: 101–116.Google Scholar
  17. 17.
    Bigger, C.A.H., J.E. Thomaszewski, and A. Dipple. 1978. 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. 80: 229–235.CrossRefGoogle Scholar
  18. 18.
    Bigger, C.A.H., J.E. Tomaszewski, A. Dipple, and R.S. Lake. 1980. Limitations of metabolic activation systems used with in vitro tests for carcinogens. Science 209: 503–505.PubMedCrossRefGoogle Scholar
  19. 19.
    Bradley, M.O., B. Bhuyan, M.C. Francis, R. Langenbach, A. Peterson, and E. Huberman. 1981. Mutagenesis by chemical agents in V79 Chinese hamster cells: a review and analysis of the literature. Mutat. Res. 87: 81–142.PubMedGoogle Scholar
  20. 20.
    Yang, S.K., J. Deutsch, and H.V. Gelboin. 1978. Benzo[a]pyrene metabolism: Activation and detoxification. In: Polycyclic Hydrocarbons and Cancer. H.V. Gelboin and P.O. Ts’o, eds. Academic Press: New York. pp. 205–224.Google Scholar
  21. 21.
    Public Health Service, National Institutes of Health. 1961–1967. Survey of compounds which have been tested for carcinogenic activity. DHEW publication No. (NIH) 73–75, PHS publication No. 149. U.S. Government Printing Office: Washington, DC.Google Scholar
  22. 22.
    Marquardt, H. 1973. Carcinogenic activity of DMBA in the liver. Cancer Res. 33: 1102–1109.Google Scholar
  23. 23.
    Nettesheim, P., and R.A. Griesemer. 1978. Experimental models for studies of respiratory tract carcinogensis. In: Pathogenesis and Therapy of Lung Cancer. C.C. Harris, ed. Marcel Dekker: New York. pp. 75–188.Google Scholar
  24. 24.
    Magee, P.N. 1979. Organ Specificity of Chemical Carcinogenesis. In: Carcinogenesis, Volume 1. G.P. Margison, ed. Pergamon Press: Oxford. pp. 213–221.Google Scholar
  25. 25.
    Summeshayes, I.C., and L.M. Franks. 1979. Effects of donor age on neoplastic transformation of adult mouse bladder epithelium in vitro. J. Natl. Cancer Inst. 62: 1017–1023.Google Scholar
  26. 26.
    Radomski, J.L., D. Greenwald, W.L. Hearn, H.L. Block, and F.M. Woods. 1978. Nitrosamine formation in bladder infections and its role in the etiology of bladder cancer. J. Urol. 120: 48–50.PubMedGoogle Scholar
  27. 27.
    Cox, C.E., A.S. Cass, and W.H. Boyce. 1969. Bladder cancer: a 26-year review. J. Urol. 101: 550–565.PubMedGoogle Scholar
  28. 28.
    Stevens, R.G., and S.H. Moolgavkor. 1979. Estimation of relative risk from vital data: Smoking and cancers of the lung and bladder. J. Natl. Cancer Inst. 63: 1351–1357.PubMedGoogle Scholar
  29. 29.
    Kinoshita, N., and H.V. Gelboin. 1978. ß-Glucuronidase catalyzed hydrolysis of benzo[a]pyrene-3-glucuronide and binding to DNA. Science 199: 307–309.PubMedCrossRefGoogle Scholar
  30. 30.
    Kuroki, T., and C. Drevon. 1978. Direct or proximate contact between cells and metabolic activation systems is required for mutagenesis. Nature 271: 368–370.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • Robert Langenbach
    • 1
  • Stephen Nesnow
    • 1
  1. 1.Carcinogenesis and Metabolism Branch, Genetic Toxicology Division, Health Effects Research LaboratoryU.S. Environmental Protection AgencyResearch Triangle ParkUSA

Personalised recommendations