Dietary Effects on DNA Methylation: Do They Account for the Hepatocarcinogenic Properties of Lipotrope Deficient Diets?

  • Judith K. Christman
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 369)


The first evidence suggesting that dietary deprivation of sources of one-carbon units could influence development of tumors is now almost fifty years old. In 1946, Copeland and Salmon reported that long-term feeding of a choline deficient diet increased the incidence of tumors in the liver and other organs of the rat. Once it was demonstrated that the peanut meal used in the diet was contaminated with aflatoxin (Newberne, 1965), it was assumed that the diet had in some way increased the sensitivity of cells to low levels of carcinogens. This supposition was supported by the demonstration that a variety of different diets deficient in choline and/or other lipotropes (methionine, folate and vitamin 12) increased the tumorigenicity of a wide range of carcinogens in liver and other organs (Rogers, 1975, 1993; Rogers and Newberne, 1980; Rogers et al., 1974; Shinozuka et al., 1978a, b; Lombardi and Shinozuka, 1979). Unequivocal demonstration that deficiency of lipotropes alone was sufficient to cause liver tumors was obtained by feeding of an amino-acid defined (AAD) diet lacking methionine and choline but supplemented with folate, vitamin B12 and homocystine (Mikol et al., 1983). In the absence of added carcinogens, this diet produced a high incidence of hepatomas in rats, yet was reported to “afford a slight protection against spontaneous tumor formation in extra-hepatic tissues.” These studies raised a number of questions that are yet to be resolved. Why is deficiency of lipotropes carcinogenic? Why is the liver the primary target tissue? Does moderate lipotrope deficiency play a significant role in development of human cancers?


Pernicious Anemia Folate Deficiency Megaloblastic Anemia Peanut Meal CCGG Site 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Antony, A., 1991, Megaloblastic anemias, in “Hematology: Basic Principles and Practice,” Hoffman R., Benz, E.J., Shattil, S.J., Furie, Cohen, H.J., eds., Churchill Livingston, New York.Google Scholar
  2. Babior, B.M., 1990, The megaloblastic anemias, in “Hematology (ed 4),” W.J. Williams, E. Beutler, A.J. Erslev, M.A. Lichtman, eds., McGraw-Hill, New York, NY.Google Scholar
  3. Baggott, J.E., Vaughn, W.H., Juliana, M.M. eto, I., Krumdieck, C.L. and Grubbs, C.J., 1992, Effects of folate deficiency and supplementation on methylnitrosourea-induced rat mammary tumors, J. Natl. Cancer Inst. 84:1740.CrossRefGoogle Scholar
  4. Bannasch, P., 1986, Preneoplastic lesions as end points in carcinogenicity testing. I. Hepatic preneoplasia, Carcinogenesis 7:689.CrossRefGoogle Scholar
  5. Bestor, T.H. and Ingram, V.M., 1983, Two DNA methyltransferases from murine erythroleukemia cells: purification and sequence specificity, Proc. Natl. Acad. Sci. U.S.A. 80:5559.CrossRefGoogle Scholar
  6. Bhave, M.R., Wilson, M.F., and Poirier, L.A., 1988, c-H-ras and c-K-ras gene hypomethylation in the livers and hepatomas of rats fed methyl-deficient, amino acid-defined diets, Carcinogenesis 9:343.CrossRefGoogle Scholar
  7. Bills, N.D., Hirichs, S.H., Morgan, R., and Cliff, A.J., 1992, Delayed tumor onset in transgenic mice fed a low-folate diet, J. Natl. Cancer Inst. 84:333.CrossRefGoogle Scholar
  8. Bishop, J.M., 1983, Cellular oncogenes and retroviruses, Annu. Rev. Biochem. 52:301.CrossRefGoogle Scholar
  9. Branda, R. F., O’Neill, I.P., Sullivan, L.M., and Albertini, R. J., 1991, Factors influencing mutation at the hprt locus in T-Lymphocytes: Women treated for breast cancer, Cancer Res. 51: 6603.Google Scholar
  10. Bremer, J., Figard, P.H., and Greenberg, D.M., 1960, The biosynthesis of choline and its relation to phospholipid metabolism, Biochim. Biophys. Acta. 43: 477.CrossRefGoogle Scholar
  11. Brinton, L.A., Gridley, G., Hrubec, Z., Hoover, R., and Fraumeni, J.F., 1989, Cancer risk following pernicious anemia, Br. J. Cancer 59:810.CrossRefGoogle Scholar
  12. Butterworth, C.E., Hatch, K.D., Gore, H., Meubler, H., and Krumdieck, C.L. 1982, Improvement in cervical displasia with folic acid therapy in users of oral contraceptives, Am. J. Clin. Nutr., 35:73.Google Scholar
  13. Carr, B.I., Reilly, J.G., Smith, S.S., Winberg, C., and Riggs, A., 1984, The tumorigenicity of 5-azacytidine in the male Fischer rat, Carcinogenesis 5:1583.CrossRefGoogle Scholar
  14. Cavenee, W.K., Dryja, T.P., Phillips, R.A., Benedict, W.F., Godbout, R., Gallie, B.L., Murphree, A.L., Strong, L.C., and White, R.L., 1983, Expression of recessive alleles by chromosomal mechansims in retinoblastoma, Nature 305:779.CrossRefGoogle Scholar
  15. Cedar, H., 1988, DNA methylation and gene activity, Cell 34:5503.Google Scholar
  16. Chandar, N., and Lombardi, B., 1988, Liver cell proliferation and incidence of hepatocellular carcinomas in rats fed consecutively a choline-devoid and a choline-supplemented diet, Carcinogenesis 2:259.CrossRefGoogle Scholar
  17. Chandar, N., Amenta, J., Kandala, J.C., and Lombardi, B., 1987, Liver cell turnover in rats fed a choline-devoid diet, Carcinogenesis 8:669.CrossRefGoogle Scholar
  18. Cheah, M.S.C., Wallace, C.D., Hoffman, R.M., 1984, Hypomethylation of DNA in human cancer cells: A site-specific change in the c-myc oncogene, J.Natl.Cancer Inst. 73:1057.Google Scholar
  19. Christman, J.K., Sheikhnejad, G., Dizik, M., Abileah, S., and Wainfan, E. 1993a Reversibility of changes in nucleic acid methylation and gene expression induced in rat liver by severe dietary methyl deficiency, Carcinogenesis 14:551.CrossRefGoogle Scholar
  20. Christman, J.K., Chen, M-L., Sheikhnejad, G., Dizik, M., Abileah, S., and Wainfan, E., 1993b, Methyl deficiency, DNA methylation, and cancer: Studies on the reversibility of the effects of lipotrope-deficient diet, J. Nutr. Biochem. 4:672.CrossRefGoogle Scholar
  21. Christman, J.K., Chen, L., Nicholson, R., and Xu, M., 1993, DNA Methylation: A cellular strategy for regulating expression of integrated hepatitis virus genes? in “Virus Strategies: Molecular Biology and Pathogenesis,” W. Doerfler, and P. Bohm, eds., VCH Verlagsgesellschaft, Weinheim, New York.Google Scholar
  22. Christman, J.K., 1984, DNA methylation in Friend Erythroleukemia Cells: The effects of chemically induced differentiation and of treatment with inhibitors of DNA methylation, Current Topics in Microbiol. and Immunol. 108: 49.CrossRefGoogle Scholar
  23. Christman, J.K., Chen, L., Sheikhnejad, G., Dizik, M., and Wainfan, E., 1991, Regulation of gene expression by DNA methylation: a link between dietary methyl deficiency and hepatocarcinogenesis, in “The Role of Nutrients in Cancer Treatment,” A. Roche, ed., Report of the 9th Ross Conference on Medical Res., Columbus.Google Scholar
  24. Clarke, S., 1992, Protein isoprenylation and methylation at carboxy-terminal cysteine residues, Annu. Rev. Biochem. 61: 131.CrossRefGoogle Scholar
  25. Comb, M. and Goodman, H.W., 1990, CpG methylation inhibits proenkephalin gene expression and binding of the transcription factor AP-2, Nucleic Acids Res. 18: 3975.CrossRefGoogle Scholar
  26. Cooper, A. J. L., 1983, Biochemistry of sulfur-containing amino acids, Annu. Rev. Biochem. 52:187.CrossRefGoogle Scholar
  27. Copeland, D.H., and Salmon, W.D., 1946, The occurrence of neoplasms in the liver, lungs, and other tissues of rats as a resuof prolonged choline deficiency, Am. J. Path. 22: 1059.Google Scholar
  28. Cox, R.D., and Irving, C.C., 1977, Inhibition of DNA synthesis by S-adenosyl-homocysteine with the production of methyl-deficient DNA in regenerating liver, Cancer Res. 37: 222.Google Scholar
  29. Cravo, M.L., Mason, J.B., Dayal, Y., Hutchinson, M. Smith, D., Selhub, J., and Rosenberg, I. H., 1992, Folate deficiency enhances the development of colonic neoplasia in dimethylhydrazine-treated rats, Cancer Res. 52:5002.Google Scholar
  30. da Costa, K., Cochary, E.F., Busztajn, J.K., Garner, S.C., and Zeisel, S. H., 1993, Accumulation of 1,2-sn-diradylglycerol with increased membrane-associated protein kinase may be the mechanism for spontaneous hepatocarcinogenesis in choline deficient rats, J. Biol. Chem. 268: 2100.Google Scholar
  31. Dizik, M., Christman, J.K., and Wainfan, E., 1991, Alterations in expression and methylation of specific genes in livers of rats fed a cancer promoting methyl-deficient diet, Carcinogenesis 12:1307.CrossRefGoogle Scholar
  32. Doerfler, W. A., 1983, DNA methylation and gene activity. Annu. Rev. Biochem. 52:93.CrossRefGoogle Scholar
  33. el-Deiry, W.S., Nelkin, B.D., Celano, P., Yen, R.W., Falco, J.P., Hamilton, S.R., and Baylin, S.B., 1991, High expression of the DNA methyltransferase gene characterizes human neoplastic cells and progression stages of colon cancer, Proc. Natl. Acad. Sci. U.S.A. 88: 3470.CrossRefGoogle Scholar
  34. Erhlich, M., Zhang, X.Y., and Inamdar, N.M., 1990, Spontaneous deamination of cytosine and 5-methylcytosine residues in DNA and replacement of 5-methylcytosine residues and cytosine residues, Mutat. Res. 238:277.CrossRefGoogle Scholar
  35. Eto, I. and Krumdieck, C.L., 1986, Role of vitamin B12 and folate deficiencies in carcinogenesis, Adv. Exptl. Biol. 206:313.Google Scholar
  36. Eloranta, T.O., 1977, Tissue distribution of S-adenosylmethionine and S-adenosylhomocysteine in the rat, effect of age, sex and methionine administration on the metabolism of S-adenosylmethionine, S-adenosylhomocysteine and polyamines, Biochem. J. 166:521.Google Scholar
  37. Farber, E. and Sarma, D.S.R., 1987, Biology of disease. Hepatocarcinogenesis: A dynamic cellular prospective, Lab. Invest. 56: 4–22.Google Scholar
  38. Farber, E., 1963 ethionine carcinogenesis, Adv. Cancer Res. 7: 380.Google Scholar
  39. Fearon, E.R., and Vogelstein, B. A., 1990, Genetic model for colorectal tumorigenesis, Cell 61:759.CrossRefGoogle Scholar
  40. Feinberg, A., and Vogelstein, B.A., 1983, Hypomethylation of ras oncogenes in primary human cancers, Biochem. Biophys. Res. Commun. 111:47.CrossRefGoogle Scholar
  41. Gama-Sosa, M.A., Slagle, V.A., Trewyn, R.W., Oxenhandler, R., Kuo, K.C., Gehrke, C.W., and Ehrlich, M., 1983, The 5-methylcytosine content of DNA from human tumors, Nucleic Acids Res. 11: 6883.CrossRefGoogle Scholar
  42. Gellerson, B. and Kempf, R., 1990, Human prolactin gene expression: positive correlation between site-specific methylation and gene activity in a set of human lymphoid cell lines, Mol. Endocrinol. 4: 1874.CrossRefGoogle Scholar
  43. Giambarresi, L. K., Katyal, S. L., and Lombardi, B., 1982, Promotion of liver carcinogenesis in the rat by a choline-devoid diet: role of liver cell necrosis and regeneration, Br. J. Cancer 46:825.CrossRefGoogle Scholar
  44. Giovannucci, E., Stampfer, M.J., Golditz, G.A., Rimm, E.B., Trichopoulos, D., Rosner, B.A., Speizer, F.E., and Willett, W.C., 1993, Folate, methionine, and alcohol intake and risk of colorectal adenoma, J. Natl. Can. Inst. 85,11:875.CrossRefGoogle Scholar
  45. Goshal, A.K., Ahluwalia, M., and Farber, E., 1983, The rapid induction of liver cell death in rats fed a choline-deficient methionine-low diet, Am. J. Pathol. 11309.Google Scholar
  46. Goshal, A.K., and Farber, E., 1984, The induction of liver cancer by a dietary deficiency of choline and methionine without added carcinogen, Carcinogenesis 5:1367.CrossRefGoogle Scholar
  47. Heimburger, D.C., Alexander, B., Birch, R., Butterworth, C.E., Bailey, W.C. and Krumdieck, L., 1988, Improvements in bronchial squamous metaplasia in smokers treated with folate and vitamin B12, J.Am. Med. Assoc. 259:1525.CrossRefGoogle Scholar
  48. Hinrichsen, L.I., Floyd, R.A., and Sudilovsky, O. 1990 Is 8-hydroxydeoxyguanosine a mediator of carcinogenesis by a choline-devoid diet in the rat liver? Carcinogenesis 11: 1879.CrossRefGoogle Scholar
  49. Herskowitz, I., 1987, Functional inactivation of genes by dominant negative mutations, Nature 329:219.CrossRefGoogle Scholar
  50. Hoover, K. K., Lynch, P.H., and Poirier, L. A., 1984, Profound postinitiation enhancement by short-term severe methionine, choline, vitamin B12 and folate deficiency of hepatocarcinogenesis in F344 rats given a single low-dose diethylnitrosamine injection, J.Natl. Cancer Inst. 73:1327.Google Scholar
  51. Horne, D.E., Cook, R.J., and Wagner, C., 1989, Effect of dietary methyl group deficiency on folate metabolism in rats, J. Nutr. 119: 618.Google Scholar
  52. Iguchi-Ariga, S.M., and Schaffner, W., 1989, CpG methylation of the cAMP-responsive enhancer/promoter sequence TGACGTCA abolishes selective factor binding as well as transcriptional activation, Genes Dev. 3:612.CrossRefGoogle Scholar
  53. Jones, P.A., Buckely, J.D., Henderson, B.E., Ross, R.K,. and Pike, M.C., 1991, From gene to carcinogen: a rapidly evolving field in molecular epidemiology, Cancer Res. 51,13:3617.Google Scholar
  54. Jost, J-P., 1993, Nuclear extracts of chicken embryos promote an active demethylation of DNA by excision repair of 5-methyldeoxycytidine, Proc. Natl. Acad. Sci. U.S.A. 90:4684.CrossRefGoogle Scholar
  55. Kennedy, E.P., and Weiss S.B., 1956, The function of cytidine coenzymes in the biosynthesis of phospholipids, J. Biol. Chem. 222:193.Google Scholar
  56. Kim, Y.I., Christman, J.K., Fleet, J.C., Cravo, M.L., Salomon, R.N., and Mason, J.B., 1994, Is global and gene specific DNA hypomethylation a mechanism by which folate deficiency enhances colorectal carcinogenesis? Abs. Amer. Gastro. Assoc. /Amer. Assoc. for the Study of Liver Diseases. New Orleans, Louisiana.Google Scholar
  57. Krumdieck, C.L., 1983, Role of folate deficiency in carcinogenesis., in “Nutritional Factors in the Induction and Maintenance of Malignancy,” Academic Press, New York.Google Scholar
  58. Kuntz, B.A., 1982, Genetic effects of deoxyribonuceotide pool imbalances, Environ. Mutagen. 4: 695.Google Scholar
  59. Kutzbach, C., Galloway, E., and Stokested, E.I., 1969, Influence of vitamin B12 and methionine on levels of folic acid compounds and folate enzymes in rat liver, Proc. Soc. Exp. Biol. Med. 124: 801.Google Scholar
  60. Lashner, B.A., Heidenreich, P.A., Su, G.L., Kane, S.V., and Hanauer, S.B., 1989, Effect of folate supplementation on the incidence of dysplasia and cancer in chronic ulcerative colitis. A case — control study, Gastroenterology 97:255.Google Scholar
  61. Locker, J., Reddy, T.V., and Lombardi, B., 1986, DNA methylation and hepatocarcinogenesis in rats fed a choline-devoid diet. Carcinogenesis 7:1309.CrossRefGoogle Scholar
  62. Loeb, L.A., and T.A. Kunkel, 1982, Fidelity of DNA synthesis, Annu. Rev. Biochem. 52: 429.CrossRefGoogle Scholar
  63. Lombardi, B., and Shinozuka, H., 1979, Enhancement of 2-acetylaminofluorene liver carcinogenesis in rats fed a choline-devoid diet, Int. J. Cancer 23:565.CrossRefGoogle Scholar
  64. Chen, M-L., Abileah, S. Wainfan, E. and Christman, J.K., 1993, Influence of folate and vitamin B12 on the effects of dietary lipotrope deficiency, Proc. Amer. Assoc. for Cancer Res. 34: 131.Google Scholar
  65. Makos, M., Nelkin, B.D., Lerman, M.I., Latif, F., Zbar, B., and Baylin, S., 1992, Distinct hypermethylation patterns occur at altered chromosome loci in human lung and colon cancer, Proc. Natl. Acad. Sci. U.S.A., 89: 1929CrossRefGoogle Scholar
  66. McMurray, W.C., 1983, “Essentials of Human Metabolism,” Harper and Row, Philadelphia.Google Scholar
  67. Meehan, R.R., Lewis, J.D., McKay, S., Kleiner, E.L., and Bird, A.P., 1989, Identification of a mammalian protein that binds specifically to DNA containing methylated CpGs, Cell 58: 499.CrossRefGoogle Scholar
  68. Mikol, Y.B, Hoover, K.L., Creasia, D., and Poirier, L.A., 1983, Hepatocarcinogenesis in rats fed methyl-deficient, amino acid-defined diets, Carcinogenesis 4: 1619.CrossRefGoogle Scholar
  69. Nakae, D., Yoshiji, H. Mizumoto, Y., Horiguchi, K. Shiraiwa, K. Tamura, K., Denda, A. and Konishi Y. 1992 High incidence of hepatocellular carcinomas induced by a choline deficient L-amino acid defined diet in rats, Cancer Res. 52:5042.Google Scholar
  70. Nambu, S., Inque, K., and Sasaki, H., 1987, Site-specific hypomethylation of the c-myc oncogene in human hepatocellular carcinoma, Jpn. J. Cancer (Gann) 78: 695.Google Scholar
  71. Newberne, P.M. and Rogers, A.E., 1980, Labile methyl groups and the promotion of cancer, nju Annu. Rev. Nutr. 6:407.CrossRefGoogle Scholar
  72. Newberne, P.M., 1965, Carcinogenicity of aflatoxin-contaminated peanut meal., in “Mycotoxins in Foodstuffs,” Massachusetts Institute of Technology, Cambridge, MA.Google Scholar
  73. Pegg, A.E., and Hibasami, H., 1979, The role of S-adenosylmethionine in mammalian polyamine synthesis, in “Transmethylation,” Elsevier-North Holland, New York.Google Scholar
  74. Perera, M.I., Betschart, J.M., Virji, M.A., Kaytal, S.L., and Shinozuka, H., 1987, Free radicanjury and liver tumor promotion, Toxicol. Pathol. 15:51.CrossRefGoogle Scholar
  75. Porta, E.A., Markeil, N. and Dorado, R.D., 1985, Chronic alcoholism enhances hepatocarcinogenicity of diethylnitrosamine in rats fed a marginally methyl-deficient diet, Hepatology 5: 1120.CrossRefGoogle Scholar
  76. Rao, P.M., Antony, A., Rajalakshmi, S., and Sarma, D.S.R., 1989, Studies on hypomethylation of liver DNA during early stages of chemical carcinogenesis in rat liver, Carcinogenesis 10:933.CrossRefGoogle Scholar
  77. Rogers, A.E., and MacDonald, R.A., 1965, Hepatic vasculature and cell proliferation in experimental cirrhosis, Lab. Invest. 14:1710.Google Scholar
  78. Rogers, A.E., Sanchez, O., Feinsod, F.M., and Newberne, P.M., 1974, Dietary enhancement of nitrosamine carcinogenesis. Cancel Res. 34:96.Google Scholar
  79. Rogers, A.E., 1975, Variable effects of a lipotrope-deficient high-fat diet on chemical carcinogenesis in rats, Cancer Res. 35:2469.Google Scholar
  80. Rogers, A.E., and Newberne, P.M., 1980, Lipotrope deficiency in experimental carcinogenesis, Nutr. Cancer 2:104.CrossRefGoogle Scholar
  81. Rogers, A.E., 1993, Chemical carcinogenesis in methyl deficient rat. J. Nutr. Biochem. 4: 666.CrossRefGoogle Scholar
  82. Rowley, J.D., 1990, Molecular cytogenetics: Rosetta stone for understanding cancer — Twenty-ninth G.H.A. Clowes Memorial Award Lecture, Cancer. Res. 50:3816.Google Scholar
  83. Rushmore, T.H., Ghazarian, D.M., Subrahmanyan, V., Farber, E., and Goshal, A.K., 1987, Probable free radical effects on rat liver nuclei during early hepatocarcinogenesis with a choline-devoid low-methionine diet, Cancer Res. 47: 6731.Google Scholar
  84. Schmidt, M., Haaf, T., and Grunert, D., 1990, 5-Azacytidine-induced undercondensations in human chromosomes, Human Genet. 67:257.CrossRefGoogle Scholar
  85. Selhub, J., Seyhoum, E., Pomfret, E.A. and Zeisel, S.H., 1991, Effects of choline deficiency and methotrexate treatment upon folate content and distribution, Cancer Res. 51:16.Google Scholar
  86. Shen, J.C., Rideout, W.M,. and Jones, P.A., 1994, High frequency mutagenesis by a DNA methyltransferase, Cell 71:1073.CrossRefGoogle Scholar
  87. Shinozuka, H., Kaytal, S.L., and Lombardi, B., 1978a, Azaserine carcinogenesis: Organ susceptibility change in rats fed a diet devoid of choline, Int. J. Cancer 22:36.CrossRefGoogle Scholar
  88. Shinozuka, H., Lombardi, B., and Sell, S., 1978b, Enhancement of ethionine liver carcinogenesis in rats fed a choline-devoid diet, J. Natl. Cancer Inst. 61:813.Google Scholar
  89. Shivapurkar, N., and Poirier, L.A., 1983, Tissue levels of S-adenosylmethionine and S-adenosylhomocysteine in rats fed methyl-deficient diets for one to five weeks, Carcinogenesis 4:1052.CrossRefGoogle Scholar
  90. Sutherland, G., 1988, The role of nucleotides in human fragile site expression, Mut. Res. 200: 207.CrossRefGoogle Scholar
  91. Tanaka, K., Appella, E., and Jay, G., 1983, Developmental activation of the H-2K gene is correlated with an increase in DNA methylation, Cell 35: 457.CrossRefGoogle Scholar
  92. Trautner, T.A., 1984, “Methylation of DNA,” Current Topics in Microbiology and Immunology, 108, Springer-Verlag, Berlin.Google Scholar
  93. Usdin, E., Borchardt, R.T., and Creveling, C.R., 1982, “Biochemistry of S-Adenosylmethionine and Related Compounds,” Macmillan Press Ltd., London.Google Scholar
  94. Vance, J.E. and Vance, D.E., 1985, The role of phosphatidylcholine biosynthesis in the secretion of lipoproteins from hepatocytes. Can. J. Biochem, Cell Biol. 63: 870.CrossRefGoogle Scholar
  95. Wainfan, E., Kilkenny, M. and Dizik, M. 1988 Comparison of methyltransferase activities of pair-fed rats given adequate or methyl-deficient diets, Carcinogenesis, 9:861.CrossRefGoogle Scholar
  96. Wainfan, E., Dizik, M., Stender, M. and Christman, J.K., 1989, Rapid appearance of hypomethylated DNA in livers of rats fed cancer-promoting, methyl-deficient diets, Cancer Res. 49:4094.Google Scholar
  97. Wainfan, E., Dizik, M., and Balis, M.E., 1984, Increased activity of rat liver N2-guanine tRNA methyltransferase II in response to liver change, Biochim. Biophys. Acta 799: 288.CrossRefGoogle Scholar
  98. Wainfan, E., Dizik, M., Hluboky M., and Balis, M.E., 1986, Altered tRNA methylation in rats and mice fed lipotrope-deficient diets, Carcinogenesis 7:473.CrossRefGoogle Scholar
  99. Wang, R.Y., Zhang, X.Y., and Ehrlich, M., 1986, A human DNA binding protein is methylation-specific and sequence-specific, Nucl. Acids Res. 14:1599.CrossRefGoogle Scholar
  100. Watt, F., Molloy, P.L. 1988 Cytosine, methylation prevents binding to DNA of a Hela cell transcription factor required for optimal expression of the adenovirus major late promoter, Genes Dev. 2: 1136.CrossRefGoogle Scholar
  101. Wickremasinghe R.G. and Hoffbrand A.V., 1980, Reduced rate of DNA replication fork movement in megaloblastic anemia. J Clin. Invest. 65,1:26.CrossRefGoogle Scholar
  102. Wilson, M.J., Shivapurkar, N. and Poirier, L.A., 1984, Hypomethylation of hepatic nuclear DNA in rats fed with a carcinogenic methyl-deficient diet, Biochem. J. 218:987.Google Scholar
  103. Wilson, V.L. and Jones, P.A., 1983, Inhibition of DNA methylation by chemical carcinogens in vitro, Cell 32:239.CrossRefGoogle Scholar
  104. Wu, A.-L., and Windmueller, H. G., 1979, Relative contribution by liver and intestine to individual plasma apolipoproteins in the rat, J. Biol. Chem. 254:7316.Google Scholar
  105. Yao, Z., and Vance, D., 1988, The active synthesis of phophatidycholine is required for very low density lipoprotein secretion from rat hepatocytes, J. Biol. Chem. 263: 2998.Google Scholar
  106. Yokoyama, S., Sells, M.A., Reddy, T.V., and Lombardi, B., 1985, Hepatocarcinogenic and promoting action of a choline-devoid diet in the rat, Cancer Res. 45:2384.Google Scholar
  107. Zapisek, W.F., Cronin, G.M., Lyn-Cook, B.D. and Poirier, L.A., 1992, The onset of oncogene hypomethylation in the livers of rats fed methyl-deficient, amino-acid defined diets, Carcinogenesis 13: 1869.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Judith K. Christman
    • 1
  1. 1.Molecular Oncology ProgramMichigan Cancer FoundationDetroitUSA

Personalised recommendations