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The Role of Folate, Choline, and Methionine in Carcinogenesis Induced by Methyl-Deficient Diets

  • Susanne M. Henning
  • Marian E. Swendseid
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 399)

Abstract

In humans, deficiencies of choline and methionine are not likely to occur except for an occasional methyl deficiency as evidenced by low plasma choline levels and development of fatty livers in some patients given longterm parenteral nutrition (Burt et al. 1980, Tayek et al. 1990 and Buchman et al. 1991). However, folate deficiency is a problem in many population subgroups such as pregnant women, adolescents, elderly people (Sauberlich 1990 and Joosten et al. 1993), and alcoholics (Shaw et al. 1989). The participation of folate in methionine regeneration and other methyl transfers links folate metabolism closely to methyl metabolism (Krumdieck, 1991). In rats a deficiency of choline and methionine and its effect on hepatocellular carcinoma in the absence of carcinogens has been studied extensively. However study of possible involvement of folate deficency in carcinogenesis mediated through alterations in methyl metabolism has been somewhat neglected. Recent reports indicating an increased risk of cancer and precancerous lesions of various types in humans associated with low folate intakes or low red blood cell folate levels increase the relevance of such investigations (Giovannucci, E. et al. 1993, Butterworth, C.E. et al. 1992).

Keywords

Folate Deficiency PARP Activity Choline Deficient Nontumorous Liver Tissue Methyl Metabolism 
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.

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References

  1. Abate, C., Patel, L., Rauscher III, F.J. & Curran, T. (1990) Redox regulation of Fos and Jun DNA-binding activity in vitro Science 249: 1157–1161PubMedCrossRefGoogle Scholar
  2. Amstad, P., Crawford, D., Muehlmatter, D., Zbinden, I., Larsson, R. & Cerutti, P. (1990) Oxidants stress induces the proto-oncogenes, C-fos and C-myc in mouse epidermal cells. Bull Cancer 77: 501–502.PubMedGoogle Scholar
  3. Amstad, P., Krupitza, G. & Cerutti, P.A. (1992) Mechanism of c-fos induction by active oxygen. Cancer Res. 52: 3952–3960.PubMedGoogle Scholar
  4. Antony, A., Rao, P.M., Rajalakshmi, S., & Sarma, D.S.R. (1987) Hypomethylation of DNA during eraly stages of chemical carcinogenesis. Proc. Am. Ass. Cancer Res. 28, 104.Google Scholar
  5. Banni, S., Corongiu, F.R, Dessi, M.A., Iannone, A., Lombardi, B., Tomasi, A., & Vannini, V. Free radicals and lipid peroxidation in liver of rats kept on a diet devoide of choline, Free Rad Res. Comms. 7: 233–240, 1989.CrossRefGoogle Scholar
  6. Banni, S., Salgo, M.G., Evans, R.W., Corongiu, F.P. & Lombardi, B. Conjugated diene and trans fatty acids in tissue lipids of rats fed an hepatocarcinogenic choline-devoid diet. Carcinogenesis 11: 2053–2057, 1990.PubMedCrossRefGoogle Scholar
  7. Barak, A.J., Tuma, D.J. & Beckenhauer, H.C. Methotrexate hepatotoxicity. J. Am. Coll. Nutr. 3: 93–96, 1984.PubMedGoogle Scholar
  8. Bhave, M.R., Wilson, M.J. & 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: 343–348.PubMedCrossRefGoogle Scholar
  9. Bird, C.L., Swendseid, M.E., Witte, J.S., Shikany, J.M., Hunt, I.F., Frankl, H.D., Lee, E.R., Longnecker, M.P. & Haile, R.W. (1995) Red cell and plasma folate, folateconsumption, and the risk of colorectal polyps. Cancer Epidem. Biomarker Prevention (submitted).Google Scholar
  10. Buchman, A., Jenden, D., Roch, M. & Rice, K, (1991) Plasma choline levels in long term TPN patients. FASEB J. 9:A1452.Google Scholar
  11. Burt, M.E., Hanin, L. and Brennan, M.F. (1980) Choline deficiency associated with total parenteral nutrition. Lancet 2, 638–639.PubMedCrossRefGoogle Scholar
  12. Butterworth, C.E., Hatch, K.D., Macaluso, M., Cole, P., Sauberlich, H.E., Soong, S.-J., Borst, M., Baker, V.V. (1992) Folate deficiency and cervical dysplasia. JAMA 267: 528–533.PubMedCrossRefGoogle Scholar
  13. Butterworth, C.E., Jr., Hatch, K.D., Mueller, G.H., Krumdieck, CL. (1982) Improvement in cervical dysplasia associated with folic acid therapy in users of oral contraceptives. Am. J. Clin Nutr. 35: 73–82.PubMedGoogle Scholar
  14. Carson, D.A., Seto, S., Wasson, D.B. and Carrera, C.J. (1986) DNA strand breaks, NAD metabolism, and programmed cell death. Exp. Cell Res., 164, 273–281.PubMedCrossRefGoogle Scholar
  15. 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, 9, 259–263.PubMedCrossRefGoogle Scholar
  16. Chandar, N., Lombardi, B. & Locker, J. (1989) c-myc gene amplification during hepatocarinogenesis by a choline-devoid diet. Proc. Natl. Acad. Sci, USA 86: 2703–2707.PubMedCrossRefGoogle Scholar
  17. Christman, J.K., Sheikhnejad, G., Dizik, M., Abileah, S. & Wainfan, E. (1993) Reversebility of changes in nucleic acid methylation and gene expression induced in rat liver by severe dietary methyl deficiency. Carcinogenesis 14: 551–557.PubMedCrossRefGoogle Scholar
  18. 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: 5002–5006.PubMedGoogle Scholar
  19. DaCosta, K.-A., Cochary, E.F., Blusztajn, J.K., Garner, S.C and Zeisel S.H. (1993) Accumulation of 1,2-sn-diradylglycerol with increased membrane-associated protein kinase C may be the mechanism for spontaneous hepatocarcinogenesis in choline-deficient rats. J. Biol. Chem. 268: 2100–2106.Google Scholar
  20. Denda, A., Rao, P.M., Rajalakshmi, S., & Sarma, D.S.R. (1985) 5-Azacytidine potentiates initiation induced by carcinogens in rat liver. Carcinogenesis 6: 145–146.PubMedCrossRefGoogle Scholar
  21. Denda, A., Tang, Q., Endoh, T., Tsujiuchi, T., Horiguchi, K., Noguchi, O., Mizumotot, Y, Nakae, D & Konishi, Y (1994) Prevention by acetylsalicylic acid of liver cirrhosis and carcinogenesis as well as generation of 8-hydroxydeoxyguanosine and thiobarbituric acid-reactive substances caused by a choline-deficient, 1-amino acid-defiened diet in rats. Carcinogenesis 15: 1279–1283.PubMedCrossRefGoogle Scholar
  22. Dizik, M., Christman, J.K. & Wainfan, E. (1991) Alterations in expression and methylation of specific genes in livers of rats fed a cancer promoting methyl-deficient diet. Carcinogenesis 12: 1307–1312.PubMedCrossRefGoogle Scholar
  23. Feinberg, A.P. & Vogelstein, B. (1983) Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 301: 89–92.PubMedCrossRefGoogle Scholar
  24. Feinberg, A.P., Gehrke, C.W., Kuo, K.C & Ehrlich, M. (1988) Reduced genomic 5-methylcytosine content in human colonic neoplasia. Cancer Res. 48: 1159–1161.PubMedGoogle Scholar
  25. Freudenheim, J.L., Graham, S., Marshall, J.R., Haughey, B.P., Cholewinski, S., Wilinson, G. (1991) Folate intake and carcinogenesis of the colon and rectum. Int. J. Epidemiol. 20: 368–374.PubMedCrossRefGoogle Scholar
  26. Ghoshal, A.K., Rushmore, T.H., Buc-Calderon, P., Roberfroid, M. & Farber, E. Prevention by free radical scavenger AD5 of prooxidant effects of choline deficiency. Free Radical Biol Med 8:3–7, 1990.CrossRefGoogle Scholar
  27. Ghoshal, A.K. and Farber, E. (1984) The induction of liver cancer by dietary deficiency of choline and methionine without added carcinogens. Carcinogenesis, 5, 1367–1370.PubMedCrossRefGoogle Scholar
  28. Ghoshal, A.K., Rushmore, T.H. & Farber, E. (1987) Initiation of carcinogenesis by a dietary deficiency of choline in the absence of added carcinogens. Cancer Let. 36: 289–296.CrossRefGoogle Scholar
  29. Ghoshal, A.K. and Farber, E. (1993) Biology of disease. Choline deficiency, lipotrope deficiency and the develoment of liver disease including liver cancer: a new perspective. Lab. Inv., 68, 255–260.Google Scholar
  30. Ghoshal, A.K., Rushmore, T.H., Buc-Calderon, P., Roberfroid, M. and Farber, E. (1990) Prevention by free radical scavenger AD5 of peroxidant effects of choline deficiency. Free Rad. Biol. Med. 8, 3–7.PubMedCrossRefGoogle Scholar
  31. 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: 825–829.PubMedCrossRefGoogle Scholar
  32. Giovannucci, E., Stampfer, M.J., Colditz, G.A., Rimm, E.B., Trichopoulos, D., Rosner, B.A., Speizer, F.E., Willett, W.C. (1993) Folate, methionine, and alcohol intake and risk of colorectal adenoma. J. Nat. Cancer Inst. 85:875–884.PubMedCrossRefGoogle Scholar
  33. Goelz, S.E., Vogelstein, B., Hamilton, S.R. & Feinberg, A.R (1985) Hypomehtylation of DNA from bengin and malignant human colon neoplasms. Science 228: 187–190.PubMedCrossRefGoogle Scholar
  34. Halliwell, B. & Gutteridge, J.M.C. (1984) Oxygen toxicity, oxygen radicals, transition metals and disease. biochem. J. 219: 1–14.PubMedGoogle Scholar
  35. Heimburger, D.C., Alexander, C.B., Birch, R., Butterworth, C.E., Bailey, W.C., Krumdieck, C.L. (1988) Improvement in bronchial squamous metaplasia in smokers treated with folate and vitamin B12. JAMA 259:1525–1530.PubMedCrossRefGoogle Scholar
  36. Henning, S.M., McKee, R.W. and Swendseid, M.E. (1989) Hepatic poly (ADP ribose) polymerase activity in methyl donor- deficient rats. J. Nutr., 119, 1528–1531.PubMedGoogle Scholar
  37. Henning, S.M., McKee, R.W. and Swendseid, M.E. (1989) Hepatic content of S-adenosylmethionine, S-adenosylhomocysteine and glutathione in rats receiving treatments modulationg methyl donor availability. J. Nutr., 119, 1478–1482.PubMedGoogle Scholar
  38. Hinrichsen, L., West, M., Floyd, R. & Sudilovsky, O. (1991) Liver 8-hydroxydeoxyguanosine (8-OHdG) is not increased in PVG rats, resistant to promotion by a choline-devoid (CD) diet. Proc. Am. Assoc. Cancer Res. 32: 899A.Google Scholar
  39. Hinrichsen, L.I., Sudilovsky, E.C, Roggero, E., Jiang, S.-H. & Sudilovsky, O. (1993) Differntial responses of two inbred rat strains to a choline-deficient diet during liver carcinogenesis. Carcinogenesis 14: 1951–1956.PubMedCrossRefGoogle Scholar
  40. James, S.J., Cross, D.R. and Miller B.J. (1992) Alterations in nucleotide pools in rats fed diets deficient in choline, methionine and/or folic acid. Carcinogenesis, 13, 2471–2474.PubMedCrossRefGoogle Scholar
  41. James, S.J., Yin, L. and Swendseid, M.E. (1989) DNA strand break accumulation, thymidylate synthesis and NAD levels in lymphocytes from methyl donor-deficient rats. J. Nutr., 119, 661–664.PubMedGoogle Scholar
  42. Jaskiewicz, K., Marasas, W.F.O., Lazarus,C, Beyers, A.D., Van Helden, P. D. (1988) Association of esophageal cytological abnormalities with vitamin and lipotrope deficiencies in populations at risk for esophageal cancer. Anticancer Res. 8: 711–716.PubMedGoogle Scholar
  43. Joosten, E., Van den Berg, A., Riezler, R., Naurath, H.J., Lindenbaum, J., Stahler, S.P. & Allen, R.H. (1993) Metabolic evidence that deficiencies of vitamin B-12 (cobalamin), foalte, and vitamin B-6 occur commonly in elderly people. Am. J. Clin. Nutr. 58: 468–476.PubMedGoogle Scholar
  44. Kim Y-L, Miller, J.W., DaCosta, K-A., Nadeau, M., Smith, D., Selhub, J., Zeisel, S.H. and Mason, J.B. (1994) Severe folate deficiency causes secondary depletion of choline and phosphocholine in rat liver. J. Nutr. 124, 2197–2203, 1994.Google Scholar
  45. Krumdieck, C.L. (1991) Localized folate deficiency and cancer. In: Vitamins and Cancer prevention (eds.), Wiley-Liss Inc. pp39–49.Google Scholar
  46. Larson, R. & Cerutti, P. (1989) Translocation and enhancement of phosphotransferase activity of protein kinase C following exposure of mouse epidermal cells to oxidants. Cancer Res. 49: 5627–5632.Google Scholar
  47. Lashner, B.A. (1993) kRed blood cell folate is associated with the development of dysplasia and cancer in ulcerative colitis. J. Cancer Res. Clin. Oncol. 119: 549–554.Google Scholar
  48. Lautier, D., Lagneux, J., Thibodeau, J., Menard, L. and Poirier, G.G. (1993) Molecular and biochemical features of poly (ADP-ribose) metabolism. Mol. Cell. Biochem., 122, 171–193.PubMedCrossRefGoogle Scholar
  49. Locker, J., Reddy, T.V & Lombardi, B. (1986) DNA methylation and hepatocarcinogenesis in rats fed a choline-devoid diet. Carcinogenesis, 7: 1309–1312.PubMedCrossRefGoogle Scholar
  50. Mikol,Y.B., Hoover, K.L., Creasia, D. and Poirier, L.A.(1983) Hepatocarcinogenesis in rats fed methyl-deficient L-amino defined diet in rats. Cancer Res., 52, 5042–5045.Google Scholar
  51. Mizumoto, Y, Nakae, D., Yoshiji, H., Andoh, N., Horiguchi, K., Endoh, T., Kobayashi, E., Tsujiuchi, T., Shimoji, N., Denda, A., Tsujii, T., Nagao, M., Wakabayashi, K. & Konishi, Y Inhibitory effects of 2-O-octadecylascorbic acid and other vitamin C and E derivatives on the induction of enzyme-altered putative preneoplastic lesions in the livers of rats fed a choline-deficient, L-amino acid-defined diet. Carcinogenesis 15: 241–246, 1994.Google Scholar
  52. Muehlematter, D., Larsson, R. & Cerutti, P. Active oxygen induced DNA stran breakage and poly ADP-ribo-sylation in promotable and non-promotable JB6 mouse epidermal cells. Carcinogenesis 9: 239–245, 1988.PubMedCrossRefGoogle Scholar
  53. Nakae, D., Yoshiji, H., Mizumoto, Y, Horiguchi, K., Shiraiwa, K., Tamura, K., Denda, A. and Karishi, Y (1992) High incidence of hepatocelluar carcinomas induced by a choline deficient L-amino acid defined diet in rats. Cancer Res. 52: 5042–5045.PubMedGoogle Scholar
  54. Nakae, D., Yoshiji, H., Maruyama, H., Kinugasa, T., Denda, A., & Konishi, Y. Production of both 8-hydroxy-deoxyguanosine in liver DNA and gamma-glutamyltransferase-positive hepatocellular lesions in rats given a choline-deficient, L-amino acid-defined diet. Jpn.J.Cancer Res. 81:1081–1084, 1990.PubMedGoogle Scholar
  55. Nakae, D., Mizumoto, Y., Yoshiji, H., Andoh, N., Horiguchi, K., Shiraiwa, K., Kobayashi, E., Endoh, T., Shimoji, N., Tamura, K., Tsujiuchi, T., Dend, A. & Konishi, Y Different roles of 8-hydroxydeoxy-guanosine formation and 2-thiobarbituric acid-reacting substance generation in the early phase of liver carcinogenesis induced by a choline-deficient, l-amino acid-defined diet in rats. JpnJ.Cancer Res. 85: 499–505, 1994.Google Scholar
  56. Poirier, L.A., (1994) Methyl group deficiency in hepatocarcinogenesis. Drug Metabol. Reviews 26: 185–199.Google Scholar
  57. Rogers, A.E., Akhtar, R., Zeisel, S.H. (1990) Procarbazine carcinogenicity in methotrexate-treated or lipot-rope-deficient male rats. Carcinogenesis 11: 1491–1495.PubMedCrossRefGoogle Scholar
  58. Rushmore, T.H., Lim, Y.P., Farber, E. & Ghoshal, A.K. Rapid lipid peroxidation in the nuclear fraction of rat liver induced by a diet deficient in choline and methionine. Cancer Letters, 24: 251–255, 1984.PubMedCrossRefGoogle Scholar
  59. Rushmore, T.H., Farber, E., Ghoshal, A.K., Parodi, S., Pala, M. and Taningher, M. (1986) A choline-devoid diet, carcinogenic in the rat, induces DNA damage and repair. Carcinogenesis, 7, 1677–1680.PubMedCrossRefGoogle Scholar
  60. Rushmore, T.H., Ghazarian, D.N., Subrahmanyan, V., Farber, E. & Ghoshal AmK. Probable free radical effects on rat liver nuclei during early hepatocarcinogenesis with a choline-devoid low methionine diet. Cancer Res 47: 6731–6740, 1987.PubMedGoogle Scholar
  61. Saito, R., Palomba, L., Rao, K.N. & Lombardi, B. (1991) resistance of female Fischer-344 rats to the hepatonecrogenic and hepatocarcinogenic actions of a choline-devoid diet. Carcinogenesis 12: 1451–1457.PubMedCrossRefGoogle Scholar
  62. Saito, R., Jahnke-Spinnenweber, E., Shinozuka, H. & Lombardi, B. (1994) On the role of compensatory mitogenesis in the hepatocarcinogenicity of choline and multiple-lipotrope devoid diets. Carcinogenesis 15: 1413–1419.PubMedCrossRefGoogle Scholar
  63. Saito, M., Kato, H., Tsuchida, T., Konaka, C. (1995) Chemoprevention effects on bronchial squamous metaplasia by foalte and vitamin B12 in heavy smokers. Chest 106: 496–499.CrossRefGoogle Scholar
  64. Sauberlich, H. E. (1990) Evaluation of folate nutrition in population groups. In: Folic acid metabolism in health and disease (eds) Wiley-Liss Inc. p. 211–235.Google Scholar
  65. Sawada, N., Poirier, L., Moran, S., Xu, Y.-H. & Pitot, H.C. (1990) The effect of choline and methionine deficiencies on the number and volume of dietylnitrosamine initiatio in rat liver. Carcinogenesis 11: 273–281.PubMedCrossRefGoogle Scholar
  66. Selhub, J., Seyoum, E., Pomfret, E.A.and Zeisel, S.H. (1991) Effects of choline deficiency and methotrexate treatment upon liver folate content and distribution. Cancer Res., 51, 16–21.PubMedGoogle Scholar
  67. Sharrard, R.M. Royds, J.A., Rogers, S. & Shorthouse, A.J. (1992) Patterns of methylation of the c-myc gene in human colorectal cancer progression. Br. J. Cancer 656: 667–672.CrossRefGoogle Scholar
  68. Shaw, S., Jayatilleke, E., Herbert, V, & Colman, N. (1989) Cleavage of folates during ethanol metabolism. Role of acetaldehyde/xanthine oxidase-generated superoxide. Biochem. J. 257: 277–280.Google Scholar
  69. Smith, M.L., Yeleswarapu, L., Scalamaogna, P., Locker, J. & Lombardi, B. (1993) p53 mutations in hepatocellular carcinomas induced by a choline-devoid diet in male Fischer 344 rats. Carcinogenesis 14: 503–510.PubMedCrossRefGoogle Scholar
  70. Tayek, J.A., Bistrian, B., Sheard, N.F., Zeisel, S.H. and Blackburn, G.L. (1990) Abnormal liver function in malnurished patients receiving total parenteral nutrition: a prospective randomized study. J.Am. Coll. Nutr. 9, 76–83.PubMedGoogle Scholar
  71. Tuma, D.J., Barak, A.J., Sorrell, M.F. (1975) Interaction of methotrexate with lipotropic factors in rat liver. Biochem. Pharmacol. 24: 1327–1331.PubMedCrossRefGoogle Scholar
  72. Wainfan, E., Dizik, M., Stender, M., Christman, J.K. (1989) Rapid appearance of hypomethylated DNA in livers of rats fed cancer-promoting, methyl-deficient diets. Cancer Res. 49: 4094–4097.PubMedGoogle Scholar
  73. Weinberg, W.C., Berkvits, L. & Iannaccone, P.M. (1987) The clonal nature of carcinogen-induced altered foci of y-glutamyl transpeptidase expression in rat liver. Carcinogenesis 8:565–570.PubMedCrossRefGoogle Scholar
  74. Wilson, M.J., Shivapurkar, N. & Poirier, L.A. (1984) Hypomethylation of hepatic nuclear DNA in rats fed with a carcinogenic methyl-deficient diet. Biochem. J. 218: 987–990.PubMedGoogle Scholar
  75. Yoshiji, H., Nakae, D., Mizumoto, Y, Horiguchi, K., Tamura, K., Denda, A., Tsujii, T. & Konishi, Y Inhibitory effect of dietary iron deficiency on inductions of putative preneoplastic lesions as well as 8-hydroxy-deoxyguanosine in DNA and lipid peroxidation in the livers of rats casued by exposure to a choline-deficient L-amino acid defined diet. Carcinogenesis 13: 1227–1233, 1992.PubMedCrossRefGoogle Scholar
  76. Zhang, J., Henning S.M. and Swendseid, M.E. (1993). NAD levels in tissues of methyl-folate deficient rats. FASEB J., A 727.Google Scholar
  77. Zhang, J.Z., Henning, S.M. and Swendseid, M.E. (1993) Poly (ADP-ribose) polymerase activity and DNA strand breaks are affected in tissues of niacin-deficient rats. J. Nutr., 123, 1349–1355.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1996

Authors and Affiliations

  • Susanne M. Henning
    • 1
  • Marian E. Swendseid
  1. 1.Division of Community Health SciencesUCLA, School of Public HealthPhiladelphiaUSA

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