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Cell specificity in metabolic activation of aflatoxin B1 and benzo(a)pyrene to mutagens for mammalian cells

Nature volume 276, pages 277–280 (1978)Cite this article

Abstract

ENVIRONMENTAL chemical carcinogens are usually non-reactive and have to be enzymatically activated before they can manifest their biological effects1–6. Many cell types, including those used for mutagenesis studies, are not capable of activating such procarcinogens; mutagenesis in these cells has been studied by the addition of an enzymatically active liver subcellular fraction7–9. However, these liver subcellular fractions readily activate a wide spectrum of compounds into potent mutagens including those which are not carcinogenic to the liver. In addition subcellular preparations differ from intact cells in the profile of the metabolites10,11 and DNA adducts12,13 formed after metabolism of various potent carcinogens such as aflatoxin B1 (AF), benzo(a)pyrene (BP), and 7,12-dimethylbenz(a)anthracene. These results suggest that the use of sub-cellular fractions does not truly simulate the in vivo situation and that it may be advantageous to use intact cells for metabolic activation of chemical carcinogens. Therefore, studies of carcinogen metabolism and mutagenic activity in cultured cells derived from different tissues should more truly reflect the in vivo situation and should also provide insight into the problem of tissue specificity in chemical carcinogenesis. Metabolic activation by intact cells of different carcinogens into intermediates which are mutagenic to mammalian cells has been reported4,14–19. This report compares the abilities of two different cell types, fibroblasts and liver cells derived from rats, to metabolise two carcinogens (BP, a potent skin and lung carcinogen which can also produce fibrosarcomas20, and AF, a potent liver carcinogen21) to water-soluble products, to intermediates which bind to cellular DNA, and to intermediates which are mutagenic to Chinese hamster V79 cells. Ouabain resistance was used as the genetic marker in V79 cells14,22.

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References

  1. Miller, J. A. Cancer Res. 30, 559–576 (1970).

    CAS  Google Scholar 

  2. Heidelberger, C. A. Rev. Biochem. 44, 79–121 (1975).

    Article  CAS  Google Scholar 

  3. Gelboin, H. V. Cancer Res. 29, 1272–1276 (1968).

    Google Scholar 

  4. Huberman, E. & Sachs, L. Int. J. Cancer 13, 326–333 (1974).

    Article  CAS  Google Scholar 

  5. Huberman, E. & Fogel, M. Int. J. Cancer 15, 91–98 (1975).

    Article  CAS  Google Scholar 

  6. Ames, B. N., Durston, W. E., Yamasaki, E. & Lee, F. D. Proc. natn. Acad. Sci. U.S.A. 70, 2281–2285 (1973).

    Article  ADS  CAS  Google Scholar 

  7. McCann, J. B. & Ames, B. N. Proc. natn. Acad. Sci. U.S.A. 73, 950–954 (1976).

    Article  ADS  CAS  Google Scholar 

  8. Krahn, D. F. & Heidelberger, C. Mutat. Res. 46, 27–44 (1977).

    Article  CAS  Google Scholar 

  9. Kuroki, T., Drevon, C. & Montesano, R. Cancer Res. 37, 1044–1050 (1977).

    CAS  PubMed  Google Scholar 

  10. Selkirk, J. K. J. Toxicol. environ. Health 2, 1245–1258 (1977).

    Article  CAS  Google Scholar 

  11. Decad, G. M., Hsieh, D. P. H. & Byard, J. L. Biochem. biophys. Res. Commun. 78, 279–287 (1977).

    Article  CAS  Google Scholar 

  12. Newbold, R. F., Wigley, C. B., Thompson, M. H. & Brooks, P. Mutat. Res. 43, 101–116 (1977).

    Article  CAS  Google Scholar 

  13. Bigger, C. A. H., Tomaszewski, J. E. & Dipple, A. Biochem. biophys. Res. Commun. 80, 229–235 (1978).

    Article  CAS  Google Scholar 

  14. Huberman, E. & Sachs, L. Proc. natn. Acad. Sci. U.S.A. 73, 188–192 (1976).

    Article  ADS  CAS  Google Scholar 

  15. San, R. H. C. & Williams, G. M. Proc. Soc. exp. Biol. Med. 156, 534–538 (1977).

    Article  CAS  Google Scholar 

  16. Harris, C. C., Hsu, I. C., Stoner, G. D., Trump, B. F. & Selkirk, J. K. Nature 272, 633–634 (1978).

    Article  ADS  CAS  Google Scholar 

  17. Kuroki, T. & Drevon, C. Nature 271, 368–370 (1978).

    Article  ADS  CAS  Google Scholar 

  18. Langenbach, R., Freed, H. J. & Huberman, E. Proc. natn. Acad. Sci. U.S.A. 75, 2864–2867 (1978).

    Article  ADS  CAS  Google Scholar 

  19. Hsu, I. C. et al. Proc. natn. Acad. Sci. U.S.A. 75, 2003–2007 (1978).

    Article  ADS  CAS  Google Scholar 

  20. Survey of Compounds Tested for Carcinogenic Activity (Public Health Service, National Institutes of Health, Bethesda, 1973).

  21. Wogan, G. N. in Liver Cell Cancer (eds Camerson, H. M., Linsell, D. A. & Warwick, G. P.) 121–151 (North-Holland, New York, 1976).

    Book  Google Scholar 

  22. Baker, R. M. et al. Cell 1, 9–21 (1974).

    Article  Google Scholar 

  23. Laishes, B. A. & Williams, G. M. In Vitro 12, 521–532 (1976).

    Article  CAS  Google Scholar 

  24. Huberman, E., Selkirk, J. K. & Heidelberger, C. Cancer Res. 31, 2161–2167 (1971).

    CAS  PubMed  Google Scholar 

  25. Burke, M. D., Vadi, H., Jernstrom, B. & Orrenius, S. J. biol. Chem. 252, 6424–6431 (1977).

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Eppley Institute for Cancer Research, and Biology Division, Oak Ridge National Laboratory,

    ROBERT LANGENBACH

  2. Eppley Institute for Cancer Research, University of Nebraska Medical Center, Omaha, Nebraska, 68105

    HEATHER J. FREED

  3. University of Tennessee-Oak Ridge Graduate School of Biomedical Sciences, and Biology Division, Oak Ridge National Laboratory,

    DINA RAVEH

  4. Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, 37830

    ELIEZER HUBERMAN

Authors
  1. ROBERT LANGENBACH
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  2. HEATHER J. FREED
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  3. DINA RAVEH
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  4. ELIEZER HUBERMAN
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LANGENBACH, R., FREED, H., RAVEH, D. et al. Cell specificity in metabolic activation of aflatoxin B1 and benzo(a)pyrene to mutagens for mammalian cells. Nature 276, 277–280 (1978). https://doi.org/10.1038/276277a0

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