Carcinogenesis and DNA Hypomethylation in Methyl-Deficient Animals

  • Lionel A. Poirier
  • Mary J. Wilson
  • Narayan Shivapurkar
Part of the Experimental Biology and Medicine book series (EBAM, volume 12)


The current increasing interest in the possible role of normal DNA methylation in carcinogenesis has sprung from three major sources: (1) cell culture studies on the role of DNA methylation in cell differentiation; (2) hypomethylation of specific genes in a variety of cancers; and (3) liver cancer causation in methyl-deficient rats. Studies on the role of DNA methylation in mammalian cell differentiation conducted by Christman et al., 1977, and Razin and Riggs, 1980, led to the postulate that undermethylation of the C5 position of cytosine may play a determining role in cancer causation (Holliday, 1979; Riggs and Jones, 1983). Feinberg and Vogelstein (1983b) showed that the genes coding for human growth hormone, α-globin, and γ-globin in human tumors were undermethylated compared to the same genes in the corresponding normal tissues. Subsequent studies have extended these observations to include other tumors and genes (Hoffman, 1984). Finally, dietary deprivation of the methyl donors methionine and choline had been shown to induce liver carcinomas in rats (Copeland and Salmon, 1946). Although these findings were accepted for a period of nearly 10 years, the subsequent demonstration of aflatoxin contamination in the peanut meal-based diets used to produce the methionine- and choline-deficiency, led credence in these findings to be suspended (Newberne, 1965). However, a second system to produce liver tumors in association with a methyl-deficient state was seen by the chronic administration of ethionine to rats (Farber, 1963).


Aflatoxin Contamination Syngeneic Host Chronic Feeding Methyl Insufficiency Liver Tumor Formation 
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  1. Brown, J., Wilson, M. J., and Poirier, L. A. (1983) Carcinogenesis 4, 173–177.CrossRefGoogle Scholar
  2. Chiang, P. K. and Cantoni, G. L. (1979) Biochem. Pharm. 28, 1897.PubMedCrossRefGoogle Scholar
  3. Christman, J. K., Price, P., Pedrinan, L., and Acs, G. (1977) Eur. J. Biochem. 81, 53.PubMedCrossRefGoogle Scholar
  4. Copeland, D. H. and Salmon, W. D. (1946) Am. J. Pathol. 22, 1059.Google Scholar
  5. Farber, E. (1963) Adv. Cancer Res. 7, 383.PubMedCrossRefGoogle Scholar
  6. Feinberg, A. P. and Vogelstein, B. (1983a) Biochem. Biophys. Res. Commun. 111, 47.PubMedCrossRefGoogle Scholar
  7. Feinberg, A. P. and Vogelstein, B. (1983b) Nature 301, 89.PubMedCrossRefGoogle Scholar
  8. Ghoshal, A. K. and Farber, E. (1984) Carcinogenesis 5, 1367.PubMedCrossRefGoogle Scholar
  9. Groffen, J., Heistercamp, N., Blennerhassett, G., and Stephenson, J. R. (1983) Virology 126, 213.PubMedCrossRefGoogle Scholar
  10. Hoffman, R. M. (1984) Biochim. Biophys. Acta 738, 49.PubMedGoogle Scholar
  11. Holliday, R. (1979) Brit. J. Cancer 40, 513.PubMedCrossRefGoogle Scholar
  12. Hyde, C. L. and Poirier, L. A. (1982) Carcinogenesis 3, 309.PubMedCrossRefGoogle Scholar
  13. Kerbel, R. S., Frost, P., Liteplo, R. G., and Fidler, R. J. (1985) Proc. Am. Assoc. Cancer Res. 26, 394.Google Scholar
  14. McGeady, M. L., Jhappan, C, Ascione, R., and VandeWoude, G. F. (1983) Mol. Cell. Biol. 3, 305.PubMedGoogle Scholar
  15. Mikol, Y. B., Hoover, K. L., Creasia, D., and Poirier, L. A. (1983) Carcinogenesis 4, 1619.PubMedCrossRefGoogle Scholar
  16. Mikol, Y. B. and Poirier, L. A. (1981) Cancer Letters 13, 195.PubMedCrossRefGoogle Scholar
  17. Newberne, P. M. (1965) in Mycotoxins in Foodstuffs (Wogan, G. N., Ed.) pp. 187–208, MIT Press, Cambridge, MA.Google Scholar
  18. Newberne, P. M., Nauss, K. M., and DeCamargo, J. (1983) Cancer Res. 43, 2426s–2634s.Google Scholar
  19. Poirier, L. A., Shivapurkar, N., Hyde, C. L., and Mikol, Y. B. (1982) in Biochemistry of S-Adenosylmethionine and Related Compounds (Usdin, E., Borchardt, R. T. and Creveling, C. R., Eds.) pp. 283–286, MacMillan Press, Ltd., London.Google Scholar
  20. Poirier, L. A., Mikol, Y. B., Hoover, K., and Creasia, D. (1984) Proc. Am. Assoc. Cancer Res. 25, 132.Google Scholar
  21. Razin, A. and Riggs, A. D. (1980) Science 210, 604.PubMedCrossRefGoogle Scholar
  22. Riggs, A. D. and Jones, P. A. (1983) Adv. Cancer Res. 40, 1.PubMedCrossRefGoogle Scholar
  23. Rogers, A. E. and Newberne, P.M. (1980) Nutrition and Cancer 2, 104.CrossRefGoogle Scholar
  24. Sells, M. A., Kaytal, S. L., Sells, S., Shinozuka, H., and Lombardi, B. (1979) Brit. J. Cancer 40, 274.PubMedCrossRefGoogle Scholar
  25. Shivapurkar, N. and Poirier, L. A. (1983) Carcinogenesis 4, 1051.PubMedCrossRefGoogle Scholar
  26. Shivapurkar, N., Wilson, M. J., and Poirier, L. A. (1984) Carcinogenesis 5, 989.PubMedCrossRefGoogle Scholar
  27. Wilson, M. J., Shivapurkar, N., and Poirier, L. A. (1984) Biochem. J. 218, 987.PubMedGoogle Scholar
  28. Wilson, M. J., Bare, R. M., Kwiecinski, E. D., and Poirier, L. A. (1985) Proc. Am. Assoc. Cancer Res. 26, 506.Google Scholar

Copyright information

© The Humana Press Inc. 1986

Authors and Affiliations

  • Lionel A. Poirier
    • 1
  • Mary J. Wilson
    • 1
  • Narayan Shivapurkar
    • 1
  1. 1.Nutrition and Metabolism Section, Laboratory of Comparative CarcinogenesisNational Cancer Institute, FCRFFrederickUSA

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