Ethionine in the Analysis of the Possible Separate Roles of Methionine and Choline Deficiencies in Carcinogenesis

  • Amiya K. Ghoshal
  • D. S. R. Sarma
  • Emmanuel Farber

Abstract

The importance of ethionine, the ethyl analogue of methionine, as a metabolic probe to study the possible roles of methionine and choline in liver carcinogenesis has been briefly reviewed. Ethionine-induced liver carcinogenesis is similar in many aspects, including initiation, promotion, and progression, to carcinogenesis with other agents. However, the special role of methionine in preventing virtually all metabolic and pathologic effects of ethionine, including liver cancer, places ethionine in a special position. On the basis of these observations and our current knowledge about choline deficiency in the genesis of liver cancer, we proposed that choline and methionine play separate but overlapping roles in the initiation and promotion of liver carcinogenesis.

Keywords

Methionine Choline Pyrene Candida Homocysteine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    P. M. Newberne, A. E. Rogers, and K. M. Nauss, Choline, methionine and related factors in oncogenesis, in: “Nutritional Factors in the Induction and Maintenance of Malignancy,” C. E. Butterworth and M. L. Hutchinson, eds., Academic Press, New York (1983).Google Scholar
  2. 2.
    P. M. Newberne, Lipotropic factors and oncogenesis, this volume.Google Scholar
  3. 3.
    H. Shinozuka, S. L. Katyal, and M. I. R. Perera, Choline deficiency and chemical carcinogenesis, this volume.Google Scholar
  4. 4.
    L. A. Poirier, The role of methionine in carcinogenesis in vivo, this volume.Google Scholar
  5. 5.
    C. H. Best, J. M. Hershey, and M. E. Huntsman, The effect of lecithine on fat deposition in the liver of the normal rat, J. Physiol. 75:56 (1932).Google Scholar
  6. 6.
    W. Dorfler, DNA methylation and gene activity, Annu. Rev. Biochem. 52:93 (1983).CrossRefGoogle Scholar
  7. 7.
    J. A. Stekol, Biochemical basis for ethionine effects on tissue, Adv. Enzymol. 25:369 (1963).Google Scholar
  8. 8.
    E. Farber, Ethionine carcinogenesis, Adv. Cancer Res. 7:383 (1963).CrossRefGoogle Scholar
  9. 9.
    E. Farber, Ethionine fatty liver, Adv. Lipid Res. 5:119 (1967).Google Scholar
  10. 10.
    J.-H. Alix, Molecular aspects of the in vivo and in vitro effects of ethionine, an analog of methionine, Microbiol. Rev. 46:281 (1981).Google Scholar
  11. 11.
    H. Popper, J. de La Huerga, and C. Yesenick, Tumors due to prolonged ethionine feeding, Science 118:80 (1953).CrossRefGoogle Scholar
  12. 12.
    J. V. Klavins, T. D. Kinney, and N. Kaufman, Hepatic nodules resembling tumors in rats after administration and withdrawal of ethionine, Proc. Soc. Exp. Biol. Med. 89:540 (1955).Google Scholar
  13. 13.
    E. Farber, Carcinoma of the liver in rats fed ethionine, Arch. Pathol. 62:445 (1956).Google Scholar
  14. 14.
    W. R. Leopold, J. A. Miller, and E. C. Miller, Comparison of some carcinogenic, mutagenic and biochemical properties of S-vinyl-homocysteine and ethionine, Cancer Res. 42:4364 (1981).Google Scholar
  15. 15.
    H. Tsuda, G. Lee, and E. Farber, The induction of resistant hepatocytes as a new principle for a possible short-term in vivo test for carcinogens, Cancer Res. 40:1157 (1980).Google Scholar
  16. 16.
    H. Shinozuka, B. Lombardi, S. Sell, et al., Early histological and functional alterations of ethionine liver carcinogenesis in rats fed a choline-devoid diet, Cancer Res. 38:1092 (1978).Google Scholar
  17. 17.
    H. Shinozuka, B. Lombardi, S. Sell, et al., Enhancement of ethionine liver carcinogenesis in rats fed a choline-devoid diet, J. Natl. Cancer Inst. 61:813 (1978).Google Scholar
  18. 18.
    E. Farber, Similarities in the sequence of early histologic changes induced in the liver of the rat by ethionine, 2-acetylaminofluorene and 3’-methyl-4-dimethylaminoazobenzene, Cancer Res. 16:142 (1956).Google Scholar
  19. 19.
    E. Farber, The pathology of experimental liver cell cancer, in: “Liver Cell Cancer,” H. M. Cameron, D. A. Linsell, G. P. Warwick, eds., Elsevier/North Holland Biomedical Press, Amsterdam (1976).Google Scholar
  20. 20.
    R. J. Pienta, J. A. Poiley, and W. B. Lebherz III, Morphological transformation of early passage golden Syrian hamster embryo cells derived from cryopreserved primary cultures as a reliable in vitro bioassay for identifying diverse carcinogens, Int. J. Cancer 19:642 (1977).CrossRefGoogle Scholar
  21. 21.
    K. K. Gyi, Non-mutational induction of transformation associated phenotypes in Syrian hamster fibroblasts by L-ethionine, Proc. Am. Assoc. Cancer Res. 23:77 (1982).Google Scholar
  22. 22.
    J. D. Brown, M. J. Wilson, and L. A. Poirier, Neoplastic conversion of rat liver epithelial cells in culture by ethionine and S-adeno-sylethionine, Carcinogenesis 4:173 (1983).CrossRefGoogle Scholar
  23. 23.
    U. I. Heine, M. J. Wilson, and E. F. Munoz, Characterization of rat liver cells transformed in culture by DL-ethionine, In Vitro 20:291 (1984).CrossRefGoogle Scholar
  24. 24.
    E. Farber, S. Parker, and M. Gruenstein, The resistance of putative premalignant liver cell populations, hyperplastic nodules, to the acute cytotoxic effects of some hepatocarcinogens, Cancer Res. 36:3879 (1976).Google Scholar
  25. 25.
    L. Eriksson, M. Ahluwalia, J. Spiewak, et al., Distinctive biochemical pattern associated with resistance of hepatocytes in hepatocyte nodules during liver carcinogenesis, Environ. Health Perspect. 49:171 (1983).CrossRefGoogle Scholar
  26. 26.
    E. Farber, The biochemistry of preneoplastic liver: A common metabolic pattern of hepatocyte nodules, Can. J. Biochem. Cell. Biol. 62:486 (1984).CrossRefGoogle Scholar
  27. 27.
    M. W. Roomi, R. K. Ho, D. S. R. Sarma, et al., A common biochemical pattern in preneoplastic hepatocyte nodules generated in four different models in the rat, Cancer Res. 45:564 (1985).Google Scholar
  28. 28.
    B. Lombardi and H. Shinozuka, Enhancement of 2-acetylaminofluorene liver carcinogenesis in rats fed a choline-devoid diet, Int. J. Cancer 23:565 (1979).CrossRefGoogle Scholar
  29. 29.
    H. Shinozuka, S. L. Katyal, and B. Lombardi, Azaserine carcinogenesis: Organ susceptibility change in rats fed a diet devoid of choline, Int. J. Cancer 22:36 (1978).CrossRefGoogle Scholar
  30. 30.
    A. K. Ghoshal and E. Farber, The induction of resistant hepatocytes during initiation of liver carcinogenesis with chemicals in rats fed a choline deficient, methionine low diet, Carcinogenesis 4:801 (1983).CrossRefGoogle Scholar
  31. 31.
    N. Ito, M. Tatematsu, K. Nakanishi, et al., The effects of various chemicals on the development of hyperplastic liver nodules in hepatectomized rats treated with N-nitrosoethylamine or N-2-fluorenylacetamide, Gann 71:832 (1980).Google Scholar
  32. 32.
    J. McCann, E. Choi, E. Yamasaki, et al., Detection of carcinogens as mutagens in the Salmonella/microsome test: Assay of 300 chemicals, Proc. Natl. Acad. Sci. U.S.A. 72:5135 (1975).CrossRefGoogle Scholar
  33. 33.
    S. Odashima, The cooperative development in Japan of methods for screening chemicals for carcinogenicity, in: “Environmental Carcinogenesis: Occurrence, Risk Evaluation and Mechanisms,” R. Montesano, H. Bartsch, and L. Tomatis, eds., International Agency for Research on Cancer, Lyon (1976).Google Scholar
  34. 34.
    C. M. Lewis and G. M. Tarrant, Induction of mutation by 5-fluorouracil and amino acid analogues in Ustilago maydis, Mutat. Res. 12:349 (1971).CrossRefGoogle Scholar
  35. 35.
    P. J. Talmud and D. Lewis, The mutagenicity of amino acid analogues in Caprinus lagopus, Genet. Res. 23:47 (1974).CrossRefGoogle Scholar
  36. 36.
    R. Joseph and B. Sikyta, Mutagenic effect of ethionine on Candida lipolytica, Experientia 31:1410 (1975).CrossRefGoogle Scholar
  37. 37.
    J. D. Finkelstein, Regulation of methionine metabolism in mammals, in: “Transmethylation,” E. Usdin, R. T. Borchardt, and C. F. Creveling, eds., Elsevier/North Holland Biomedical Press, New York (1978).Google Scholar
  38. 38.
    Z. Brada, S. Bulba, and N. H. Altman, The influence of DL-methionine on the metabolism of S-adenosylethionine in rats chemically treated with ethionine, Cancer Res. 36:1573 (1976).Google Scholar
  39. 39.
    C. L. Hyde and L. A. Poirier, Hepatic levels of S-adenosylethionine and S-adenosylmethionine in rat and hamster during subchronic feeding of DL-ethionine, Carcinogenesis 3:309 (1982).CrossRefGoogle Scholar
  40. 40.
    M. Friedman, K. H. Shull, and E. Farber, Highly selective in vivo ethylation of rat liver nuclear protein by ethionine, Biochem. Biophys. Res. Commun. 34:857 (1969).CrossRefGoogle Scholar
  41. 41.
    R. T. Tuck and R. Cox, Ethionine causes the formation of NG-monoethylarginine in nuclear proteins from regenerating liver, Carcinogenesis 3:1477 (1982).CrossRefGoogle Scholar
  42. 42.
    P. F. Swann, A. E. Pegg, A. Hawks, et al., Evidence for ethylation of rat liver deoxyribonucleic acid after administration of ethionine, Biochem. J. 123:175 (1971).Google Scholar
  43. 43.
    R. Cox and M. T. Tuck, Alteration of methylation patterns of rat liver histones following administration of ethionine, a liver carcinogen, Cancer Res. 41:1253 (1981).Google Scholar
  44. 44.
    M. T. Tuck and R. Cox, Ethionine inhibits in vivo methylation of nuclear proteins, Carcinogenesis 3:431 (1982).CrossRefGoogle Scholar
  45. 45.
    N. Shivapurkar, M. J. Wilson, and L. A. Poirier, Hyporaethylation of DNA in ethionine-fed rats, Carcinogenesis 5:989 (1984).CrossRefGoogle Scholar
  46. 46.
    E. Farber and H. Ichinose, The prevention of ethionine-induced carcinoma of the liver in rats by methionine, Cancer Res. 18:1209 (1958).Google Scholar
  47. 47.
    E. Farber, M. V. Simpson, and H. Tarver, Studies on ethionine. II. The interf erence with lipid metabolism, J. Biol. Chem. 182:91 (1950).Google Scholar
  48. 48.
    L. I. Giambarresi, S. L. Katyal, and B. Lombardi, Promotion of liver carcinogenesis in the rat by a choline-devoid diet: Role of liver cell necrosis and regeneration, Br. J. Cancer 46:825 (1982).CrossRefGoogle Scholar
  49. 49.
    A. K. Ghoshal, M. Ahluwalia, and E. Farber, The rapid induction of liver cell death in rats fed a choline-deficient methionine-low diet, Am. J. Pathol. 113:309 (1983).Google Scholar
  50. 50.
    A. K. Ghoshal and E. Farber, The induction of liver cancer by dietary deficiency of choline and methionine without added carcinogens, Carcinogenesis 5:1367 (1984).CrossRefGoogle Scholar
  51. 51.
    Y. B. Mikol, K. L. Hoover, D. Creasia, et al., Hepatocarcinogenesis in rats fed methyl-deficient amino acid defined diets, Carcinogenesis 4:1619 (1983).CrossRefGoogle Scholar
  52. 52.
    S. Yokoyama, M. A. Sells, T. V. Reddy, et al., Hepatocarcinogenic and promoting action of a choline-devoid diet in the rat, Cancer Res. 45:2834 (1985).Google Scholar
  53. 53.
    T. Miyazawa, M. Yamaguchi, J.-H. Lee, et al., Decomposition of lipid hydroperoxide by choline and ethanolamine, Agric. Biol. Chem. 48:1375 (1984).CrossRefGoogle Scholar
  54. 54.
    T. H. Rushmore, Y. P. Lim, E. Farber, et al., Rapid lipid peroxidation in the nuclear fraction of rat liver induced by a diet deficient in choline and methionine, Cancer Lett. 24:251 (1984).CrossRefGoogle Scholar
  55. 55.
    T. H. Rushmore, A. K. Ghoshal, and E. Farber, In vivo DNA damage in rat liver after exposure to a diet deficient in choline and methionine (CMD), Proc. Am. Assoc. Cancer Res. 26:99 (1985).Google Scholar
  56. 56.
    E. Cayama, H. Tsuda, D. S. R. Sarma, et al., Initiation of chemical carcinogenesis requires cell proliferation, Nature 275:60 (1978).CrossRefGoogle Scholar
  57. 57.
    T. S. Ying, D. S. R. Sarma, and E. Farber, Role of acute hepatic necrosis in the evolution of early steps in liver carcinogenesis by diethylnitrosamine, Cancer Res. 41:2096 (1981).Google Scholar
  58. 58.
    A. Columbano, S. Rajalakshmi, and D. S. R. Sarma, Requirement of cell proliferation for the initiation of liver carcinogenesis as assayed by three different procedures, Cancer Res. 41:2079 (1981).Google Scholar
  59. 59.
    H. Shinozuka, M. A. Sells, S. L. Katyal, et al., Effects of a cholinedevoid diet on the emergence of γ-glutamyltranspeptidase-positive foci in the liver of carcinogen-treated rats, Cancer Res. 39:2515 (1979).Google Scholar
  60. 60.
    M. A. Sells, S. L. Katyal, S. Sell, et al., Induction of foci of altered, γ-glutamyltranspeptidase-positive hepatocytes in carcinogen-treated rats fed a choline-deficient diet, Br. J. Cancer 40:274 (1979).CrossRefGoogle Scholar
  61. 61.
    E. Farber, The sequential analysis of liver cancer induction, Biochim. Biophys. Acta 605:149 (1980).Google Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Amiya K. Ghoshal
    • 1
  • D. S. R. Sarma
    • 1
  • Emmanuel Farber
    • 1
  1. 1.Department of PathologyUniversity of TorontoTorontoCanada

Personalised recommendations