Vitamins and Cancer

  • Raymond J. Shamberger


Of the entire collection of chemically diverse substances classified as vitamins, vitamin A is of greatest current interest in terms of its possible role in the process of carcinogenesis. In this discussion the term vitamin A is used to describe vitamin A itself as well as its synthetic analogues of vitamin, called retinoids. The only well-understood function of vitamin A is its role in the visual cycle.


Ascorbic Acid Retinoic Acid Pernicious Anemia Thiamine Deficiency Sodium Ascorbate 
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. 1.
    Lasnitzki, I. 1963. Growth pattern of the mouse prostate gland in organ culture and its response to sex hormones, vitamin A, and 3-methylcholanthrene. Natl. Cancer Inst. Monogr. 12: 381–403.PubMedGoogle Scholar
  2. 3.
    Lasnitzki, I. 1976. Reversal of methylcholanthrene-induced changes in mouse prostates in vitro by retinoic acid and its analogues. Br. J. Cancer 34: 239–246.PubMedCrossRefGoogle Scholar
  3. 2.
    Crocker, T., and Sanders, L. 1970. Influence of vitamin A and 3,7-dimethyl-2,6-octadienal (citrol) on the effect of benzopyrene on hamster trachea in organ culture. Cancer Res. 30: 1312–1318.PubMedGoogle Scholar
  4. 4.
    Davies, R. E. 1967. Effect of vitamin A on 7,12-dimethylbenzanthracene-induced papillomas in rhino mouse skin. Cancer Res. 27: 237–241.PubMedGoogle Scholar
  5. 5.
    Bollag, W. 1972. Therapeutic effects of an aromatic retinoic acid analog on chemically induced benign and malignant epithelial tumors by vitamin A acid (retinoic acid). Eur. J. Cancer 10: 731–737.Google Scholar
  6. 6.
    Shamberger, R. J. 1971. Inhibitory effect of vitamin A on carcinogenesis. J. Natl. Cancer Inst. 47: 667–673.PubMedGoogle Scholar
  7. 7.
    Saffiotti, U., Montesano, R., and Sellakumar, A. R. 1967. Experimental cancer of the lung. Inhibition by vitamin A on the induction of tracheobronchial squamous metaplasia and squamous cell tumors. Cancer Res. 20: 857–864.Google Scholar
  8. 8.
    Cone, M. V., and Nettesheim, P. 1973. Effects of vitamin A on 3-methylcholanthrene-induced squamous metaplasia and early tumors in the respiratory tract of rats. J. Natl. Cancer Inst. 50: 1599–1604.PubMedGoogle Scholar
  9. 9.
    Nettesheim, P., and Williams, M. L. 1976. The influence of vitamin A on the susceptibility of the rat lung to 3-methylcholantherene. Infrect. J. Cancer 17: 351–357.CrossRefGoogle Scholar
  10. 10.
    Smith, D. M., Rogers, A. E., Herndon, B. J., and Newberne, P. M. 1975. Vitamin A (retinyl acetate) and benzopyrene-induced respiratory tract carcinogenesis in hamsters fed a commercial diet. Cancer Res. 35: 11–16.PubMedGoogle Scholar
  11. 11.
    Cohen, S. M., Wittenberg, J. F., and Bryan, G. T. 1976. Effect of avitaminosis A and hypervitaminosis A on urinary bladder carcinogenicity of N-4-(5-nitro-z-furyl)-2-thiazolyl formamide. Cancer Res. 56: 2334–2339.Google Scholar
  12. 12.
    Narisawa, T., Reddy, B. S., Wong, C. Q., and Weisburger, J. H. 1976. Effect of vitamin A deficiency on rat colon carcinogenesis by N-methyl-N-nitro-N nitrosoguanidine. Cancer Res. 36: 1379–1383.PubMedGoogle Scholar
  13. 13.
    Rogers, A. E., Herndon, B. J., and Newbeme, F. M. 1973. Induction by dimethylhydrazine of intestinal carcinoma in normal rats and rats fed high or low levels of vitamin A. Cancer Res. 33: 1003–1009.PubMedGoogle Scholar
  14. 14.
    Newberne, P. M., and Rogers, A. E. 1973. Rat colon carcinomas associated with aflatoxin and marginal vitamin A. J. Natl. Cancer Inst. 50: 439–448.PubMedGoogle Scholar
  15. 15.
    Chu, E. W., and Malmgren, R. A. 1965. An inhibitory effect of vitamin A on the induction of tumors of forestomach and cervix in the Syrian hamster by carcinogenic polycyclic hydrocarbons. Cancer Res. 25: 884–895.PubMedGoogle Scholar
  16. 16.
    Levine, N. S., Salisbury, R. E., Seifter, E., Walker, H. L., Mason, A. D., Jr., and Pruitt, B. A., Jr. Effect of vitamin A on tumor development in burned, unburned, and glucocorticoid-treated mice inoculated with an oncogenic virus. Experientia 15: 1309–1312.Google Scholar
  17. 17.
    Retura, G., Schittek, A., Hardy, M., Levenson, S. M., Demetriou, A., and Seifter, E. 1975. Antitumor action of vitamin A in mice with adenocarcinoma cells. J. Natl. Cancer Inst. 54: 1489–1491.Google Scholar
  18. 18.
    McMichael, H. 1975. Inhibition of growth of Shope rabbit papilloma by hypervitaminosis A. Cancer Res. 25: 1309–1312.Google Scholar
  19. 19.
    Anton, E., and Brandes, D. 1968. Lysosomes in mouse mammary tumors treated with cyclophosphamide. Distribution related to the course of disease. Cancer 21: 483–500.PubMedCrossRefGoogle Scholar
  20. 20.
    Cohen, M. H., and Carbone, P. P. 1972. Enhancement of the antitumor effects of 1,3-bis-(2-chlorethyl)-1-nitrosourea and cyclophosphamide by vitamin A. J. Natl. Cancer Inst. 48: 921–926.PubMedGoogle Scholar
  21. 21.
    Tomita, Y., Himeno, K., Nomoto, K., Endo, H., and Hirohata, T. 1982. Combined treatments with vitamin A and 5-fluorouracil and the growth of allotransplantable and syngeneic tumors in mice. J. Natl. Cancer Inst. 68: 823–827.PubMedGoogle Scholar
  22. 22.
    Prutkin, L. 1973. Antitimor activity of vitamin A acid and fluorouracil used in combination on the skin tumor, keratoacanthoma. Cancer Res. 33: 128–133.PubMedGoogle Scholar
  23. 23.
    Tani, E., Morimura, T., Kaba, K., and Itagaki, T. 1980. Preliminary study of the effects of vitamin A on antineoplastic activities of chemotherapeutic agents in glioma. Neurol. Med. Chir. (Tokyo) 20: 665–677.CrossRefGoogle Scholar
  24. 24.
    Komiyama, S., Hiroto, I., Ryu, S., Nakashima, T., Kuwano, M., and Endo, H. Synergistic combination therapy of 5-fluorouracil, vitamin A and cobalt-60 radiation upon head and neck tumors. Oncology 35: 253–257.Google Scholar
  25. 25.
    Merriman, R. L., and Bertram, J. S. 1979. Reversible inhibition by retinoids of 3-methylcholanthrene-induced neoplastic transformation in C3H/10T ½ clone 8 cells. Cancer Res. 39: 1661–1666.PubMedGoogle Scholar
  26. 26.
    Todaro, G. J., DeLarco, J. E., and Sporn, M. B. 1978. Retinoids block phenotypic cell transformation produced by sarcoma growth factor. Nature 27: 272–274.CrossRefGoogle Scholar
  27. 27.
    Lotan, R., and Nicolson, G. L. 1977. Inhibitory effeects of retinoic acid or retinyl acetate on the growth of untransformed, transformed, and tumor cells in vitro. J. Natl. Cancer Inst. 59: 1712–1722.Google Scholar
  28. 28.
    Huang, C. C., Hsueh, J. L., Chen, H. H., and Batt, T. R. 1982. Retinol (vitamin A) inhibits sister chromatid exchanges and cell cycle delay induced by cyclophosphamide and aflatoxin B-1 in Chinese hamster V 79 cells. Carcinogenesis 3: 1–5.PubMedCrossRefGoogle Scholar
  29. 29.
    Busk, L., and Ahlborg, U. G. 1980. Retinol (vitamin A) as an inhibitor of the mutagenicity of aflatoxin B-1. Toxicol. Lett. 6: 243–249.PubMedCrossRefGoogle Scholar
  30. 30.
    Busk, L., and Ahlborg, U. 1982. Retinol (vitamin A) as a modifier of 2-aminofluorene and 2-acetyl-aminofluorene mutagenesis in the Salmonella/microsome assay. Arch. Toxicol. 49: 169–174.PubMedCrossRefGoogle Scholar
  31. 31.
    Sporn, M. B., Dunlop, N. M., Newton, D. L., and Henderson, W. R. 1976. Relationship between structure and activity of retinoids. Nature 263: 110–113.PubMedCrossRefGoogle Scholar
  32. 32.
    Bollag, W. 1975. Therapy of epithelial tumors with an aromatic retinoic acid analog. Chemotherapy (Basel) 21: 236–247.Google Scholar
  33. 33.
    Port, C. D., Sporn, M. B., and Kaufman, D. G. 1975. Prevention of lung cancer in hamsters by 13-cis-retinoic acid. Proc. Am. Assoc. Cancer Res. 16: 21.Google Scholar
  34. 34.
    Grubbs, C. J., Moon, R. C., and Sporn, M. B. 1976. Suppression of DMBA-induced mammary tumorigenesis by retinyl methyl ether. Proc. Am. Assoc. Cancer Res. 17: 68Google Scholar
  35. 35.
    Todaro, G., DeLarco, J., and Sporn, M. Retinoids block phenotypic cell transformation produced by sarcoma growth factor. Nature 276: 272–274.Google Scholar
  36. 36.
    Sporn, M. B., Dunlop, N. M., Newton, D. L., and Smith, J. M. 1976. Prevention of chemical carcinogenesis by vitamin A and its synthetic analogs (retinoids). Fed. Proc. 35: 1332–1338.PubMedGoogle Scholar
  37. 37.
    Peto, R., Doll, R., Buckley, J. D., and Sporn, M. B. 1981. Can dietary beta-carotene materially reduce human cancer rates? Nature 290: 201–208.PubMedCrossRefGoogle Scholar
  38. 38.
    Mathews-Roth, M. M., Pathak, M. A., Fitzpatrick, T. B., Harber, L. H., and Kass, E. H. 1977. Beta carotene therapy for erythropoietic protoporphyria and other photosensitivity diseases. Arch. Dermatol. 113: 1229–1232.PubMedCrossRefGoogle Scholar
  39. 39.
    Shamberger, R. J. 1971. Inhibitory effect of vitamin A on carcinogenesis. J. Natl. Cancer Inst. 47: 667–673.PubMedGoogle Scholar
  40. 40.
    Seifter, E., Rettura, G., Podawer, J., and Levenson, S. M. 1982. Moloney murine sarcoma virus tumors in CBA/J mice: Chemopreventative and chemotherapeutic actions of supplemental β-carotene. J. Natl. Cancer Inst. 68: 835–840.PubMedGoogle Scholar
  41. 41.
    Sporn, M. B., Clamon, G. H., Dunlop, N. M., Newton, D. L., Smith, J. M., and Saffiotti, U. 1975. Activity of vitamin A analogues in cell cultures of mouse epidermis and organ cultures of hamster trachea. Nature 253: 47–49.PubMedCrossRefGoogle Scholar
  42. 42.
    Wilkoff, L. J., Peckham, J., Dulmadge, E. A., Mowry, R. W., and Chopra, D. P. 1976. Evaluation of vitamin A analogs in modulating epithelial differentiation of 13-day chick embryo metatarsal skin explants. Cancer Res. 36: 964–972.PubMedGoogle Scholar
  43. 43.
    Sani, B. P. 1977. Localization of retinoic acid-binding protein in nuclei. Biochem. Biophys Res. Commun. 75: 7–12.PubMedCrossRefGoogle Scholar
  44. 44.
    Wiggert, B., Russel, P., Lewis, M., and Chader, G. 1977. Differential binding to soluble nuclear receptors and effects on cell viability of retinol and retinoic acid in cultured retinoblastoma cells. Biochem. Biophys. Res. Commun. 79: 218–225.PubMedCrossRefGoogle Scholar
  45. 45.
    Sani, B. P., and Hill, D. L. 1974. Retinoic acid: A binding protein in chick embryo metatarsal skin. Biochem. Biophys. Res. Commun. 61: 1276–1281.PubMedCrossRefGoogle Scholar
  46. 46.
    Sani, B. P., and Donovan, M. K. 1979. Localization of retinoic acid-binding protein in nuclei and the nuclear uptake of retinoic acid. Cancer Res. 39: 2492–2496.PubMedGoogle Scholar
  47. 47.
    Huber, P. R., Geyer, E., Kung, W., Matter, A., Torhorst, J., and Eppenberger, U. 1978. Retinoic-acid binding protein in human breast cancer and dysplasia. J. Natl. Cancer Inst. 61: 1375–1378.PubMedGoogle Scholar
  48. 48.
    Basu, T. K., Rowland, L., Jones, L,, and Kohn, J. 1982. Vitamin A and retinol-binding protein in patients with myelomatosis and cancer of epithelial organ. Eur. J. Clin. Oncol. 18: 339–342.CrossRefGoogle Scholar
  49. 49.
    Hill, D. L., and Shih, T. W. 1974. Vitamin A compounds and analogues as inhibitors of mixed-function oxidases that metabolize carcinogenic polycyclic hydrocarbons and other compounds. Cancer Res. 34: 564–570.PubMedGoogle Scholar
  50. 50.
    Carruthers, C. 1942. The effect of carcinogens on the hepatic vitamin A stores of mice and rats. Cancer Res. 2: 168–174.Google Scholar
  51. 51.
    Genta, V. M., Kaufman, D. G., Harris, C. C., Smith, J. M., Sporn, M. B., and Saffiotti, U. 1974. Vitamin A deficiency enhances the binding of benzopyrene to tracheal epithelial DNA. Nature 247: 48–49.PubMedCrossRefGoogle Scholar
  52. 52.
    Verma, A. K., Shapas, B. G., Rice, H. M., and Boutwell, R. K. 1979. Correlation of the inhibition by retinoids of tumor-promotor-induced mouse ornithine decarboxylase activity of skin tumor promotion. Cancer Res. 39: 419–425.PubMedGoogle Scholar
  53. 53.
    Lowe, N. J., and Breeding, J. 1982. Retinoic acid modulation of ultraviolet light-induced epidermal ornithine decarboxylase activity. J. Invest. Dermatol. 78: 121–124.PubMedCrossRefGoogle Scholar
  54. 54.
    Conner, M. J., Lowe, N. J., Breeding, J. H., and Chalet, M. 1983. Inhibition of ultraviolet-B skin carcinogenesis by all-trans-retinoic acid regimens that inhibit ornithine decarboxylase induction. Cancer Res. 43: 171–174.Google Scholar
  55. 55.
    O’Brien, T. G. 1976. The induction of ornithine decarboxylase as an early possibly obligatory, event in mouse skin carcinogenesis. Cancer Res. 36: 2644–2653.PubMedGoogle Scholar
  56. 56.
    Levine, L., and Ohuchi, K. 1978. Retinoids as well as tumour promotors enhance deacylation of cellular lipids and prostaglandin production in MDCK cells. Nature 276: 274–275.PubMedCrossRefGoogle Scholar
  57. 57.
    Hill, D. L., and Grubbs, C. J. 1982. Retinoids as chemopreventive and anticancer agents in intact animals. (Review.) Anticancer Res. 2: 111–124.PubMedGoogle Scholar
  58. 58.
    Bjelke, E. 1975. Dietary vitamin A and human lung cancer. Int. J. Cancer 15: 561–565.PubMedCrossRefGoogle Scholar
  59. 59.
    MacLennan, R., DaCosta, J., Day, N. E., Law, C. H., Ng, Y. K., and Shanmugaratnam. 1977. Risk factors for lung cancer in Singapore Chinese, a population with high female incidence rates. Int. J. Cancer 20: 854–860.PubMedCrossRefGoogle Scholar
  60. 60.
    Gregor, A., Lee, P. N., Roe, F. J. C., Wilson, M. J., and Melton, A. 1980. Comparison of dietary histories in lung cancer cases and controls with special reference to vitamin A. Nutr. Cancer 2: 93–97.CrossRefGoogle Scholar
  61. 61.
    Smith, P. G., and Jick, H. 1978. Cancers among users of preparations containing vitamin A. Cancer 42: 808–811.PubMedCrossRefGoogle Scholar
  62. 62.
    Mettlin, C., Graham, S., and Swanson, M. 1979. Vitamin A and lung cancer. J. Natl. Cancer Inst. 62: 1435–1438.PubMedGoogle Scholar
  63. 63.
    Basu, TIK., Donaldson, D., Jenner, M., Williams, D. C., and Sakula, A. 1976. Plasma vitamin A in patients with bronchial carcinoma. Br. J. Cancer 33: 119–121.PubMedCrossRefGoogle Scholar
  64. 64.
    Shekelle, R. B., Liu, S., Raynor, W. J., Lepper, M., Maliza, C., and Rossof, A. H. 1981. Dietary vitamin A and risk of cancer in the Western Electric study. Lancet 2: 1185–1189.PubMedCrossRefGoogle Scholar
  65. 65.
    Graham, S., Mettlin, C., Marshall, J., Priore, R., Rzepka, T., and Shedd, D. 1981. Dietary factors in the epidemiology of cancer of the larynx. Am. J. Epidemiol. 113: 675–680.PubMedGoogle Scholar
  66. 66.
    Wynder, E. L., and Bross, I. J. 1961. A study of etiological factors in cancer of the esophagus. Cancer 14: 389–413.PubMedCrossRefGoogle Scholar
  67. 67.
    Mettlin, C., Graham, S., Priore, R., Marshall, J., and Swanson, M. 1981. Diet and cancer of the esophagus. Nutr. Cancer 2: 143–147.PubMedCrossRefGoogle Scholar
  68. 68.
    Hormozdiari, H., Day, N. E., Aramesh, B., and Mahboubi, E. 1975. Dietary factors and esophageal cancer in the Caspian littoral of Iran. Cancer Res. 35: 3493–3498.PubMedGoogle Scholar
  69. 69.
    Cook-Mazaffari, P. J., Azordegan, F., Day, N. E., Ressicand, A., Sabai, C., and Aramesh, B. 1979. Oesophageal cancer studies in the Caspian litterol of Iran: Results of a case-control study. Br. J. Cancer 39: 293–309.CrossRefGoogle Scholar
  70. 70.
    Hirayama, T. 1967. The epidemiology of cancer of the stomach in Japan with special reference to the role of the diet. in R. J. C. Harris (Ed.) Proceedings of the 9th international congress. UICC Monograph Series. Vol. 10. pp. 37–48. New York: Springer-Verlag.Google Scholar
  71. 71.
    Hirayama, T. 1977. Changing patterns of cancer in Japan with special reference to the decrease in stomach cancer mortality. in H. H. Hiatt, J. D. Watson, and J. A. Winsten (Eds.) Origins of human cancer. pp. 55–57. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory.Google Scholar
  72. 72.
    Graham, S., Schotz, W., and Martino, P. 1972. Alimentary factors in the epidemiology of gastric cancer. Cancer 30: 927–938.PubMedCrossRefGoogle Scholar
  73. 73.
    Haenszel, W., Kurihara, M., Segi, M., and Lee, R. K. C. 1972. Stomach cancer among Japanese in Hawaii. J. Natl. Cancer Inst. 49: 969–988.PubMedGoogle Scholar
  74. 74.
    Bjelke, E. 1978. Dietary factors and epidemiology of cancer of the stomach and large bowel. Aktuel Ernaehrungsmed. Klin. Prax. Suppl. 2: 10–17.Google Scholar
  75. 75.
    Schuman, L. M., Mandell, J. S., Redke, A., Seal, U., and Halberg, F. 1982. Some selected features of the epidemiology of prostatic cancer: Minneapolis-St. Paul, Minnesota case-control study, 1976–1979. in K. Magnus (Ed.) Trends in cancer incidence: Causes and practical implications. pp. 345–354. New York: Hemisphere.Google Scholar
  76. 76.
    Romney, S. L., Palan, P. R., Duttagupta, C., Wassertheil-Smollery Wylie, J., Miller, G., Slagle, N. S., and Lucido, D. 1981. Retinoids and the prevention of cervical dysplasias. Am. J. Obstet. Gynecol. 141: 890–894.PubMedGoogle Scholar
  77. 77.
    Cambien, F., Ducimetierre, P., and Richard J. 1980. Total serum cholesterol and cancer mortality in a middle-aged population. Am. J. Epidemiol. 112: 388–394.PubMedGoogle Scholar
  78. 78.
    Kark, J. D., Smith, A. H., and Hames, C. G. 1980. The relationship of serum cholesterol to the incidence of cancer in Evans County, Georgia. J. Chronic Dis. 33: 311–322.PubMedCrossRefGoogle Scholar
  79. 79.
    Wald, N., Idle, M., Boreham, J., and Bailey, A. 1980. Low serum vitamin A and subsequent risk of cancer—Preliminary results of a prospective study. Lancet 2: 813–815.PubMedCrossRefGoogle Scholar
  80. 80.
    Kark, J. D., Smith, A. H., and Hames, C. G. 1982. Serum retinol and the inverse relationship between serum cholesterol and cancer. Br. Med. J. 284: 152–154.CrossRefGoogle Scholar
  81. 81.
    Tannenbaum, A., and Silverstone, H. 1952. The genesis and growth of tumors. V. Effects of varying the level of B vitamins in the diet. Cancer Res. 12: 744–749.PubMedGoogle Scholar
  82. 82.
    Boutwell, R. K., Brush, M. K., and Rusch, H. P. 1949. The influence of vitamins of the B complex on the induction of epithelial tumors in mice. Cancer Res. 9: 747–752.PubMedGoogle Scholar
  83. 83.
    Kensler, C. J., Sugiura, K., Young, N. F., Halter, C. R., and Rhoads, C. P. 1941. Partial protection of rats by riboflavin with case in against liver cancer caused by dimethylaminoazo-benzene. Science 93: 308–310.PubMedCrossRefGoogle Scholar
  84. 84.
    Miller, J. A., and Miller, E. C. 1953. The carcinogenic aminoazo dyes. Adv. Cancer Res. 1: 339–396.PubMedCrossRefGoogle Scholar
  85. 85.
    Morris, H. P. 1947. Effects on the genesis and growth of tumors associated with vitamin intake. Ann. N.Y. Acad. Sci. 49: 119–140.CrossRefGoogle Scholar
  86. 86.
    Chan, P. C., Okamoto, T., and Wynder, E. L. 1972. Possible role of riboflavin deficiency in epithelial neoplasia. III. Induction of microsomal aryl hydrocarbon hydroxylase. J. Natl. Cancer Inst. 48: 1341–1345.PubMedGoogle Scholar
  87. 87.
    Pacernick, L. J., Soltani, K., and Lorincz, A. L. 1975. The inefficacy of riboflavin against ultraviolet-induced carcinogenesis. J. Invest. Dermatol. 65: 547–548.PubMedCrossRefGoogle Scholar
  88. 88.
    Lemonnier, F. J., Scott, J. M., and Thuong-Trieu, C. 1975. Influence of riboflavin on disturbances in tryptophan metabolism and hepatoma production after a single dose of aflatoxin B-1. J. Natl. Cancer Inst. 55: 1085–1087.PubMedGoogle Scholar
  89. 89.
    Stoerk, H. C., and Emerson, G. A. 1949. Complete regression of lymphosarcoma implants following temporary induction of riboflavin deficiency in mice. Proc. Soc. Exp. Biol. Med. 70: 703–704.PubMedGoogle Scholar
  90. 90.
    Aposhian, H. V., and Lambooy, J. P. 1951. Retardation of growth of Walker rat carcinoma 256 by administration of diethyl riboflavin. Proc. Soc. Exp. Biol. Med. 78: 197–199.PubMedGoogle Scholar
  91. 91.
    Lane, M. 1971. Induced riboflavin deficiency in treatment of patients with lymphomas and polycythemia vera. Proc. Am. Assoc. Cancer Res. 12: 85.Google Scholar
  92. 92.
    Morris, H. P., and Lippincott, S. W. 1941. Effect of pantothenic acid and growth of the spontaneous mammary carcinoma in female C3H mice. J. Natl. Cancer Inst. 2: 47–54.Google Scholar
  93. 93.
    Petering, L. J., Soltani, K., and Lorincz, A. L. 1975. The inefficacy of riboflavin against ultrainduced carcinogenesis. J. Invest. Dermatol. 65: 547–548.CrossRefGoogle Scholar
  94. 94.
    Newberne, P. M. 1965. Carcinogenicity of aflatoxin-contaminated peanut meals. in G. N. Wogen (Ed.) Mycotoxins in foodstuffs. Cambridge, Mass.: MIT Press. pp. 187–208.Google Scholar
  95. 95.
    Lombardi, B., and Shinozuka, H. 1979. Enhancement of 2-acetyLaminofluorene liver carcinogenesis in rats fed a choline-devoid diet. Int. J. Cancer 23: 565–570.PubMedCrossRefGoogle Scholar
  96. 96.
    Shinozuka, H., Katyal, S. L., and Lombardi, B. 1978. Azaserine carcinogenesis: Organ susceptibility change in rats fed a diet devoid of choline. Int. J. Cancer 22: 36–39.PubMedCrossRefGoogle Scholar
  97. 97.
    Takahashi, S., Lombardi, B., and Shinozuka, H. 1982. Progression of carcinogen-induced foci of γ-glutamyltranspeptidase-positive hepatocytes to hepatomas in rats fed a choline-deficient diet. Int. J. Cancer 29: 445–450.PubMedCrossRefGoogle Scholar
  98. 98.
    Giambarresi, L. I., 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
  99. 99.
    Reddy, T. V., Romanathan, R., Shinozuka, H., and Lombardi, B. 1983. Effects of dietary choline deficiency on the mutagenic activation of chemical carcinogens by rat liver fractions. Cancer Lett. 18: 41–48.PubMedCrossRefGoogle Scholar
  100. 100.
    Rogers, A. E. 1975. Variable effects of a lipotrope deficient, high fat diet on chemical carcinogenesis in rats. Cancer Res. 35: 2469–2474.PubMedGoogle Scholar
  101. 101.
    Morris, H. P. 1947. Effects on the genesis and growth of tumors associated with vitamin intake. Ann. N.Y. Acad. Sci. 49: 119–140.CrossRefGoogle Scholar
  102. 102.
    Basu, T. K., Dickerson, J. W. T., Raven, R. W., and Williams, D. C. 1974. The thiamine status of patients with cancer as determined by the red cell transketolase activity. Int. J. Vit. Nutr. Res. 44: 53–58.Google Scholar
  103. 103.
    De Reuck, J. L., Sieben, G. J., Sieben-Praet, M. R., Ngendahayo, P., Decoster, J. P., and Vancer Eeken, H. M. 190. Wernicke’s encephalopathy in patients with tumors of the lymphoid hemapoetic systems. Arch. Neurol. 37: 338-341.Google Scholar
  104. 104.
    Aksoy, M., Basu, T. K., Brient, J., and Dickerson, J. W. T. 1980. Thiamin status of patients treated with drug combinations containing 5-fluorouracil. Eur. J. Cancer 16: 1041–1045.PubMedGoogle Scholar
  105. 105.
    Ostryanina, A. D. 1971. Vitamin B12 and the neoplastic process. Vopr. Pitan. 29: 25–31.Google Scholar
  106. 105a.
    Temcharoen, P., Anukarahanonta, T., and Bhamarapratvi, N. 1978. Influence of dietary protein and vitamin B12 on the toxicity and carcinogenicity of aflatoxins in rat liver. Cancer Res. 38: 2185–2190.PubMedGoogle Scholar
  107. 106.
    Pegg, A. E. 1977. Formation and metabolism of alkylated nucleosides: Possible role in carcinogenesis by nitroso compounds and alkylating agents. Adv. Cancer Res. 25: 195–269.PubMedCrossRefGoogle Scholar
  108. 107.
    Day, P. L., Payne, L. D., and Dinning, J. S. 1960. Procarcinogenic effect of vitamin B12 on p-dimethylaminoazobenzene-fed rats. Proc. Soc. Exp. Biol. Med. 74: 854–857.Google Scholar
  109. 108.
    Yamamoto, R. S. 1980. Effect on vitamin B12 deficiency in colon carcinogenesis. Proc. Soc. Exp. Biol. Med. 163: 350–353.PubMedGoogle Scholar
  110. 109.
    Elsborg, L., and Masbech, J. 1979. Pernicious anemia as a risk factor in gastric cancer. Acta Intern. Med. 206: 315–318.Google Scholar
  111. 110.
    Ruddell, W. S., Bone, E. S., Hill, M. J., and Walters, C. L. 1978. Pathogenesis of gastric cancer in pernicious anemia. Lancet 1: 521–523.PubMedCrossRefGoogle Scholar
  112. 111.
    Arvanitakis, C., Holmes, F. F., and Hearne, E. A. 1979. Possible associations of pernicious anemia with neoplasia. Oncology 36: 127–129.PubMedCrossRefGoogle Scholar
  113. 112.
    Carmel, R., and Eisenberg, L. 1977. Serum B12 and transcobalamin abnormalities in patients with cancer. Cancer 40: 1348–1350.PubMedCrossRefGoogle Scholar
  114. 113.
    Einhorn, J., and Retzenstein, P. 1966. Metabolic studies of folic acid and malignancy. Cancer Res. 26: 340–343.PubMedGoogle Scholar
  115. 114.
    Roa, P. B., Lagerlof, B., Einhorn, J., and Retzenstein, P. 1965. Folic acid activity in leukemia and cancer. Cancer Res. 25: 221–224.Google Scholar
  116. 115.
    Taguchi, H., Sanada, H., Hosei, T., Hara, K., Mizukawa, I., Sezaki, T., Irino, S., Iwasaki, I., and Hiraki, K. 1974. Folic acid metabolism in Rauscher murine leukemia and effect of methotrexate on the blood picture. Acta Med. Okayama 28: 353–359.PubMedGoogle Scholar
  117. 116.
    Djerassi, I., Farber, S., Abing, E., and Neikerk, W. 1967. Continuous infusion of methotrexate in children with acute leukemia. Cancer 20: 223–242.CrossRefGoogle Scholar
  118. 117.
    Jaffe, N. 1972. Recent advances in the chemotherapy of metastatic osteogenic sarcoma. Cancer 30: 1627–2631.PubMedCrossRefGoogle Scholar
  119. 118.
    Alberto, P., Peytremann, R., Medenica, R., and Piccoli, M. B. 1978. Initial clinical experience with a simultaneous combination of 2,4-diamino-5(3,4-dichlorophenyl)-6-methylpyrimidine (DDMP) with folinic acid. Cancer Chemother. Pharmacol. 1: 101–105.PubMedCrossRefGoogle Scholar
  120. 119.
    Sirotnak, F. M., DeGraw, J. I., Moccio, D. J., and Dorick, D. M. 1978. Antitumor properties of a new folate analog, 10-deaza-aminopterin in mice. Cancer Treatm. Rep. 62: 1047–1052.Google Scholar
  121. 120.
    Kline, B. E., Rusch, H. P., Bauman, C. A., and Lavik, P. S. 1943. The effect of pyridoxine on tumor growth. Cancer Res. 3: 825–829.Google Scholar
  122. 121.
    Mihich, E., and Nichol, C. A. 1959. The effect of pyridoxine deficiency on mouse sarcoma 180. Cancer Res. 19: 279–284.PubMedGoogle Scholar
  123. 122.
    Tryfiates, G. P., and Morris, H. P. 1974. Effect of pyridoxine deficiency on tyrosine trans-aminase activity and growth of four mouse hepatomas. J. Natl. Cancer Inst. 52: 1259–1262.PubMedGoogle Scholar
  124. 123.
    Tryfiates, G. P. 1975. Effect of pyridoxine availability on the activity of serine dehydratase of normal liver, host liver, and three Morris hepatomas. J. Natl. Cancer Inst. 54: 171–172.PubMedGoogle Scholar
  125. 124.
    DiSarbo, D. M., Paavola, L. G., and Litwack, G. 1982. Pyridoxine resistance in a rat hepatoma cell line. Cancer Res. 42: 2362–2370.Google Scholar
  126. 125.
    DiDorbo, D. M., and Litwack, G. 1982. B6 kills hepatoma cells in culture. Nutr. Cancer 3: 216–222.CrossRefGoogle Scholar
  127. 126.
    Pruzansky, J., and Axelrod, A. E. 1955. Antibody production to diphtheria toxoid in vitamin deficiency states. Proc. Soc. Exp. Biol. Med. 89: 323–325.PubMedGoogle Scholar
  128. 127.
    Axelrod, A. E., and Hopper, S. 1960. Effects of pantothenic acid, pyridoxine and thiamine deficiencies upon antibody formation to influenza virus PR-8 in rats. J. Nutr. 72: 325–330.PubMedGoogle Scholar
  129. 128.
    Trakatellis, A. C., Stinebring, W. R., and Axelrod, A. E. 1963. Studies on systemic reacitivy to purified protein and derivative (PPD) and endotoxin. 1. Systemic reactivity to PPD in pyridoxine-deficient guinea pigs. J. Immunol. 91: 39–45.PubMedGoogle Scholar
  130. 129.
    Axelrod, A. E., Fisher, B., Fisher, E., Lee, Y. C. P., and Walsh, P. 1958. Effect of a pyridoxine deficiency on skin grafts in the rat. Science 127: 1388–1389.PubMedCrossRefGoogle Scholar
  131. 130.
    Axelrod, E. E., and Trakatellis, A. C. 1964. Induction of tolerance to skin homografts by administering splenic cells by pyridoxine-deficient mice. Proc. Soc. Exp. Biol. Med. 116: 206–210.PubMedGoogle Scholar
  132. 131.
    Gailani, S. D., Holland, N. F., Nussbaum, A., and Olson, K. B. 1968. Chemical and biochemical studies of pyridoxine deficiency in patients with neoplastic diseases. Cancer 21: 975–988.PubMedCrossRefGoogle Scholar
  133. 132.
    Shapiro, D. M., and Gellhorn, A. 1951. Combinations of chemical compounds in experimental therapy. Cancer Res. 11: 35–41.PubMedGoogle Scholar
  134. 133.
    Korytnyk, W., Hakala, M. T., Potti, P. G. G., Angelino, N., and Chang, S. C. 1976. On the inhibitory activity of 4-vinyl analogs of pyridoxal: Enzyme and cell culture studies. Biochemistry 15: 5458–5466.PubMedCrossRefGoogle Scholar
  135. 134.
    Potera, C., Rose, D. P., and Brown, R. R. 1977. Vitamin B6 deficiency in cancer patients. Am. J. Clin. Nutr. 30: 1677–1679.PubMedGoogle Scholar
  136. 135.
    Rakieten, N., Gordon, B. S., Beaty, A., Cooney, D. A., Davis, R. D., and Schein, P. S. 1971. Pancreatic islet tumors produced by the combined action of streptozotocin and nicotinamide. Proc. Soc. Exp. Biol. Med. 137: 280–283.PubMedGoogle Scholar
  137. 136.
    Shoentel, R. 1977. The role of nicotinamide and of other modifying factors in diethylnitrosamine carcinogenesis. Cancer 40: 1833–1840.CrossRefGoogle Scholar
  138. 137.
    Barra, R., Randolph, V., Sumas, M. E., Lanighan, K., and Lea, M. A. 1982. Effects of nicotinamide, isonicotinamide and bleomycin on DNA synthesis and repair in rat hepatocytes and hepatoma cells. J. Natl. Cancer Inst. 69: 1353–1357.PubMedGoogle Scholar
  139. 138.
    Nduka, N., Skidmore, C. J., and Shall, S. 1980. The enhancement of cytotoxicity of N-methyl-N-nitrosourea and of γ-radiation by inhibitors of poly (ADP-ribose) polymerase. Eur. J. Biochem. 105: 525–530.PubMedCrossRefGoogle Scholar
  140. 139.
    Smulson, M. E., Schein, P., Mullins, D. W., and Sudhakar, S. 1977. A putative role for nicotinamide adenine dinucleotide-promoted nuclear protein modification in the antitumor activity of N-methyl-N-nitrosourea. Cancer Res. 37: 3006–3012.PubMedGoogle Scholar
  141. 140.
    Shapiro, D. M., Dietrich, L. S., and Shies, M. D. 1957. Quantitative biochemical differences between tumor and host as a basis of cancer chemotherapy. Cancer Res. 17: 600–604.PubMedGoogle Scholar
  142. 141.
    Barclay, R. K., and Phillips, M. A. 1966. Effects of 6-diazo-5-oxo-l-norleucine and other tumour inhibitors on the biosynthesis of NAD in mice. Cancer Res. 26: 282–286.PubMedGoogle Scholar
  143. 142.
    Shimoyama, M. S., Yamaguchi, K., and Gholson, R. K. 1967. Enzymic lesions of nicotinamide adenine dinucleotide biosynthesis in hepatomas and in azo dye carcinogenesis. Cancer Res. 27: 578–583.PubMedGoogle Scholar
  144. 143.
    Brown, R. R., Price, J. M., Freidell, G., and Burney, S. W. 1969. Tryptophan metabolism in patients with bladder cancer. Geographical differences. J. Natl. Cancer Inst. 43: 295–301.PubMedGoogle Scholar
  145. 144.
    Zeitlin, I., and Smith, A. N. 5-Hydroxyindoles and kinins in the carcinoid and dumping syndromes. Lancet 2: 986–996.Google Scholar
  146. 145.
    Basu, T. K., Raven, R. W., Bate, C., and Williams, O. C. 1973. Excretion of 5-hydroxyindole acetic acid and N-methylnicotinamide in advanced cancer patients. Eur. J. Cancer 9: 527–528.PubMedGoogle Scholar
  147. 146.
    Szent-Gyorgyi, A. 1928. Observations of the functions of peroxidase systems and the chemistry of the adrenal cortex. Biochem. J. 22: 1387–1409.PubMedGoogle Scholar
  148. 147.
    Baker, E. M., Hodges, R. E., Hood, J., Sauberlich, H. E., March, S. C., and Canham, J. E. 1971. Metabolism of 14C and 3H-labeled l-ascorbic acid in human scurvy. Am. J. Clin. Nutr. 24: 444–454.PubMedGoogle Scholar
  149. 148.
    Hornig, D., Vuilleumier, J. P., and Hartmann, P. 1980. Absorption of large, single, oral intakes of ascorbic acid. Int. J. Vit. Nutr. Res. 50: 309–314.Google Scholar
  150. 149.
    Shamberger, R. J. 1972. Increase of peroxidation in carcinogenesis. J. Natl. Cancer Inst. 48: 1491–1497.PubMedGoogle Scholar
  151. 150.
    Slaga, T. J., and Bracken, W. M. 1977. The effects of anti-oxidants on skin tumor initiation and aryl hydrocarbon hydroxylase. Cancer Res. 37: 1631–1635.PubMedGoogle Scholar
  152. 151.
    Sadek, I. A., and Abdelmegid, N. 1982. Ascorbic acid and its effect on the skin of Bufo regularis. Oncology 39: 399–400.PubMedCrossRefGoogle Scholar
  153. 152.
    Abul-Hajj, Y. J., and Kelliher, M. 1982. Failure of ascorbic acid to inhibit growth of transplantable and dimethylbenzanthracene induced rat mammary tumors. Cancer Lett. 17: 67–73.PubMedCrossRefGoogle Scholar
  154. 153.
    Shoyab, M. 1981. Inhibition of the binding of 7, 12-dimethylbenzanthracene to DNA of murine epidermal cells in culture by vitamin A and vitamin C. Oncology 38: 187–192.PubMedCrossRefGoogle Scholar
  155. 154.
    Dunham, W. B., Zuckerkandl, E., Reynolds, R., Willoughby, R., Marcuson, R., Barth, R., and Pauling, L. 1982. Effects of intake of l-ascorbic acid on the incidence of dermal neoplasms induced in mice by ultraviolet light. Proc. Natl. Acad. Sci. (USA) 79: 7532–7536.CrossRefGoogle Scholar
  156. 155.
    Schlegel, J. U., Pipkin, G. E., Nishumura, R., and Schultz, G. N. 1969. The role of ascorbic acid in the prevention of bladder tumor formation. Trans. Am. Assoc. Genitourinary Surg. 61: 85–89.Google Scholar
  157. 156.
    Boyland, E., and Williams, D. C. 1956. Metabolism of tryptophan in patients suffering from cancer of the bladder. Biochem. J. 64: 578–582.PubMedGoogle Scholar
  158. 157.
    Price, J. M., Wear, J. B., Brown, R. R., Satter, E. J., and Olson, C. 1960. Studies on etiology of bladder carcinoma. J. Urol. 83: 376–382.PubMedGoogle Scholar
  159. 158.
    Price, J. M., Wear, J. B., Brown, R. R., Satter, E. J., and Olson, C. 1963. Studies on eitology of carcinoma of the urinary bladder. J. Urol. 83: 376–382.Google Scholar
  160. 159.
    Benassi, C. A., Perissinotto, B., and Allegri, G. 1963. The metabolism of tryptophan in patients with bladder cancer and other urological diseases. Clin. Chem. Acta 8: 822–831.CrossRefGoogle Scholar
  161. 160.
    Schlegel, J. U. 1975. Proposed users of ascorbic acid in the prevention of bladder carcinoma. Ann. N.Y. Acad. Sci. 258: 432–437.PubMedCrossRefGoogle Scholar
  162. 161.
    Pipkin, G. E., Nishimura, R., Banowsky, L., and Schlegel, J. U. 1967. Stabilization of urinary 3-hyroxyanthranilic acid by the oral administration of l-ascorbic acid. Proc. Soc. Exp. Biol. Med. 126: 702–704.Google Scholar
  163. 162.
    Soloway, M. S., Cohen, S. M., Dekernion, J. B., and Persky, L. 1975. Failure of ascorbic acid to inhibit FANFT-induced bladder cancer. J. Urol. 113: 483–486.PubMedGoogle Scholar
  164. 163.
    Mirvish, S. S., Wallace, L., Eagen, M., and Shubik, P. 1972. Ascorbate-nitrite reaction: Possible means of blocking the formation of carcinogenic compounds. Science 177: 65–68.PubMedCrossRefGoogle Scholar
  165. 164.
    Mirvish, S. S., Cardesa, A., Wallcave, L., and Shubik, P. 1975. Induction of mouse lung adenomas by amines or ureas plus nitrite and by N-nitroso compounds: Effect of ascorbate, gallic acid, thiocyanate and caffeine. J. Natl. Cancer Inst. 55: 633–636.PubMedGoogle Scholar
  166. 165.
    Mirvish, S. S. 1981. Inhibition of the formation of carcinogenic N-nitroso compounds by ascorbic acid and other compounds. in J. H. Burchenal and H. F. Oettgen (Eds.) Cancer achievements, challenges and prospects for the 1980’s. Vol. 1. pp. 557–587. New York: Grune & Stratton.Google Scholar
  167. 166.
    Ivankovic, S., Preussmann, R., Schmahl, D., and Zeller, J. W. 1975. Prevention by ascorbic acid of in vivo formation of N-nitroso compounds. in P. Bogovski and E. A. Walker (Eds.) N-nitroso compounds in the environment. IARC Scientific Publications #9. Lyons, France: International Agency for Research on Cancer.Google Scholar
  168. 167.
    Raineri, R., and Weisburger, J. H. 1975. Reductions of gastric carcinogens with ascorbic acid. Ann. N.Y. Acad. Sci. 258: 181–189.PubMedCrossRefGoogle Scholar
  169. 168.
    Archer, M. C., Tannenbaum, S. R., Tan, T., and Weisman, M. 1975. Reaction of gastric carcinogens with ascorbic acid and its relaton to nitrosamine formation. J. Natl. Cancer Inst. 54: 1203–1205.PubMedGoogle Scholar
  170. 169.
    Chan, W. C., and Fong, Y. Y. 1970. Ascorbic acid prevents liver tumor production by aminopyrine and nitrite in the rat. Int. J. Cancer 20: 268–270.CrossRefGoogle Scholar
  171. 170.
    Bodansky, O., Wroblewski, F., and Markardt, B. 1952. Concentrations of ascorbic acid in plasma and white cells of patients with cancer and non-cancerous chronic disease. Cancer 5: 678–684.PubMedCrossRefGoogle Scholar
  172. 171.
    Basu, T. K., Raven, R. W., Dickerson, J. W. T., and Williams, D. C. 1974. Leucocyte ascorbic acid and urinary hydroxyproline levels in the patients bearing breast tumor with skeletal metastases. Eur. J. Cancer 10: 507–511.PubMedGoogle Scholar
  173. 172.
    Krasner, N., and Dymock, I. W. 1974. Ascorbic acid deficiency in malignant diseases: A clinical and biochemical study. Br. J. Cancer 30: 142–145.PubMedCrossRefGoogle Scholar
  174. 173.
    Gross, J. 1959. Formatin of collagen: IV. Effect of vitamin C deficiency on the natural salt-extractable collagen of skin. J. Exp. Med. 109: 557–569.PubMedCrossRefGoogle Scholar
  175. 174.
    Cameron, E., and Pauling, L. 1973. Ascorbic acid and the glycosaminoglycans: An orthomolecular approach to cancer and other diseases. Oncology 27: 181–192.PubMedCrossRefGoogle Scholar
  176. 175.
    DeClerck, Y. A., and Jones, P. A. 1980. Effect of ascorbic acid on the resistance of the extracellular matrix to hydrolysis by tumor cells. Cancer Res. 40: 3228–3231.PubMedGoogle Scholar
  177. 176.
    Cameron, E., and Campbell, B. 1974. The orthomolecular treatment of cancer. II. Clinical trial of high-dose ascorbic acid supplements in advanced human cancer. Chem. Biol. Interact. 9: 285–315.PubMedCrossRefGoogle Scholar
  178. 177.
    Cameron, E., and Pauling, L. 1978. Supplemental ascorbate in the supportive treatment of cancer: Re-evaluation of prolongation of survival times in terminal cancer patients. Proc. Natl. Acad. Sci. (USA) 75: 4538–4542.CrossRefGoogle Scholar
  179. 178.
    Creagen, E. T., Moertel, C. G., O’Fallon, J. R., Schutt, A. J., O’Connell, M. J., Rubin, J., and Frytak, S. 1979. Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer. N. Engl. J. Med. 301: 687–690.CrossRefGoogle Scholar
  180. 179.
    DeCosse, J. J., Adams, M. B., Kuzma, J. F., LoGerfo, P., and Condon, R. E. 1975. Effect of ascorbic acid on rectal polyps of patients with familial polyposis. Surgery 78: 608–612.PubMedGoogle Scholar
  181. 180.
    Bussey, H. J. R., DeCasse, J. J., Deschner, E. E., Eyers, A. A., Lesser, M. L., Morson, B. C., Ritchie, S. M., Thomson, J. P. S., and Wadsworth, J. 1982. A randomized trial of ascorbic acid in polyposis coli. Cancer 50: 1434–1439.PubMedCrossRefGoogle Scholar
  182. 181.
    Meinsma, L. 1964. Nutrition and cancer. Voeding 25: 357–365.PubMedGoogle Scholar
  183. 182.
    Higginson, J. 1966. Etiological factors in gastro-intestinal cancer in man. J. Natl. Cancer Inst. 37: 527–545.PubMedGoogle Scholar
  184. 183.
    Haenszel, W., and Correa, P. 1975. Developments in the epidemiology of stomach cancer over the past decade. Cancer Res. 35: 3452–3459.PubMedGoogle Scholar
  185. 184.
    Bjelke, E. 1978. Dietary factors and the epidemiology of cancer of the stomach and large bowel. Akt. Ernaehrungsmed. Klin. Prax. Suppl. 2: 10–17.Google Scholar
  186. 185.
    Weisburger, J. H., Marquardt, H., Mower, H. F., Hirota, N., Mori, H., and Williams, G. 1980. Inhibition of carcinogenesis: Vitamin C and the prevention of gastric cancer. Prev. Med. 9: 352–361.PubMedCrossRefGoogle Scholar
  187. 186.
    Kolonel, L. N., Nomura, A. M. Y., Hirohata, T., Hankin, J. H., and Hinds, M. W. 1981. Association of diet and place of birth with stomach cancer incidence in Hawaii, Japanese and Caucasians. Am. J. Clin. Nutr. 34: 2478–2485.PubMedGoogle Scholar
  188. 187.
    Dungal, N., and Sigurjonsson, J. 1967. A pilot study of dietary habits in two districts differing markedly in respect of mortality from gastric cancer. Br. J. Cancer 21: 270–276.PubMedCrossRefGoogle Scholar
  189. 188.
    Hirayama, T. 1979. Diet and cancer. Nutr. Cancer 1: 67–81.CrossRefGoogle Scholar
  190. 189.
    Bjelke, E. 1976. Dietary vitamin A and human lung cancer. Int. J. Cancer 15: 561–565.CrossRefGoogle Scholar
  191. 190.
    MacLennan, R., DaCosta, J., Day, N. E., Law, C. H., Ng, Y. K., and Shanmugaratnam, K. 1977. Risk factors for lung cancer in Singapore Chinese, a population with high female incidence rates. Int. J. Cancer 20: 854–860.PubMedCrossRefGoogle Scholar
  192. 191.
    Mettlin, C., Graham, S., and Swanson, M. 1979. Vitamin A and lung cancer. J. Natl. Cancer Inst. 62: 1435–1438.PubMedGoogle Scholar
  193. 192.
    Graham, S., Dayal, H., Rohrer, T., Swanson, M., Sulty, H., Shedd, D., and Fischman, S. 1977. Dentition, diet, tobacco, and alcohol in the epidemiology of oral cancer. J. Natl. Cancer Inst. 59: 1611–1618.PubMedGoogle Scholar
  194. 193.
    Graham, S., Schotz, W., and Martino, P. 1972. Alimentary factors in the epidemiology of gastric cancer. Cancer 4: 927–938.CrossRefGoogle Scholar
  195. 194.
    Mettlin, C., Graham, S., Priore, R., Marshall, J., and Swanson. 1981. Diet and cancer of the esophagus. Nutr. Cancer 2: 143–147.PubMedCrossRefGoogle Scholar
  196. 195.
    Graham, S., Mettlin, C., Marshall, J., Priore, R., Rzepka, T., and Shedd, D. 1982. Dietary factors in the epidemiology of cancer of the larynx. Am. J. Epidemiol. 113: 675–680.Google Scholar
  197. 196.
    Graham, S., Marshall, J., Mettlin, C., Rzepka, T., Nemoto, T., and Byers, T. 1982. Diet in the epidemiology of breast cancer. Am. J. Epidemiol. 116: 68–75.PubMedGoogle Scholar
  198. 197.
    Wassertheil-Smoller, S., Romney, S. L., Wylie-Rosett, J., Slagle, S., Miller, G., Lucido, D., Duttagupta, C., and Palan, P. R. 1981. Dietary vitamin C and uterine cervical dysplasia. Am. J. Epidemiol. 114: 714–724.PubMedGoogle Scholar
  199. 198.
    Ziegler, R. G., Morris, L. E., Blot, W. J., Pattern, L. M., Hoover, R., and Fraumeni, J. F. 1981. Esophageal cancer among black men in Washington D.C. II. Role of Nutrition. J. Natl. Cancer Inst. 67: 1199–1206.PubMedGoogle Scholar
  200. 199.
    Jain, M., Cook, G. M., Davis, F. G., Grace, M. G., and Howe, G. R., and Miller, A. B. 1980. A case-control study of diet and colo-rectal cancer. Int. J. Cancer 26: 757–768.PubMedCrossRefGoogle Scholar
  201. 200.
    Ramirez, I., Richie, E., Wang, Y., and Van Eys, J. 1980. Effect of ascorbic acid in vitro on lymphocyte reactivity to mitogens. J. Nutr. 110: 2207–2215.PubMedGoogle Scholar
  202. 201.
    Poydock, M. E., Fardon, J. C., Gallina, D., Ferro, V., and Heher, C. 1979. Inhibiting effect of vitamin C and B12 on the mitotic activity of ascites tumors. Exp. Cell Biol. 47: 210–211.PubMedGoogle Scholar
  203. 202.
    Dixit, A., and Rao, R. 1980. Influence of ascorbic acid on action of DMBA on DNA, RNA and protein levels in mouse liver following partial hepatectomy. Indian J. Exp. Biol. 18: 1494–1496.PubMedGoogle Scholar
  204. 203.
    Bissell, M. J., Hatie, C., Farson, D. A., Schwarz, R. J., and Soo, W. 1980. Ascorbic acid inhibits replication and infectivity of avian RNA tumor virus. Proc. Natl. Acad. Sci. (USA) 77: 2711–2715.CrossRefGoogle Scholar
  205. 204.
    Schwerdt, P. R., and Sthwerdt, C. E. 1978. Effect of ascorbic acid on rhinovirus replication in W1-38 cells. Proc. Soc. Exp. Biol. Med. 148: 1237–1243.Google Scholar
  206. 205.
    Bullough, W. S., and Ryotomaa, T. 1965. Mitotic homeostatis. Nature 205: 573–578.CrossRefGoogle Scholar
  207. 206.
    Edgar, J. A. 1970. Dehydroascorbic acid and cell division. Nature 227: 24–26.PubMedCrossRefGoogle Scholar
  208. 207.
    Price, C. E. 1966. Ascorbate stimulation of RNA synthesis. Nature 212: 1481.PubMedCrossRefGoogle Scholar
  209. 208.
    Freidel, J. F., Fardon, J. C., Tsuchiya, Y., and Nutini, L. G. 1979. In vitro effect of D-isoascorbic acid and betaine hydrate alone and in combination on normal and malignant cells. Exp. Cell Biol. 47: 463–469.PubMedGoogle Scholar
  210. 209.
    Park, C. H., Amare, M., Savin, M. A., and Hoogstraten, B. 1980. Growth suppression of human leukemic cells in vitro by l-ascorbic acid. Cancer Res. 40: 1062–1065.PubMedGoogle Scholar
  211. 210.
    Bishun, T. K., Basu, T. K., Metcalfe, S., and Williams, D. C. 1978. The effect of ascorbic acid (vitamin C) on two tumor cell lines in culture. Oncology 35: 160–162.PubMedCrossRefGoogle Scholar
  212. 211.
    Bram, S. Froussard, P., Guichard, M., Jasmin, C., Augery, Y., Sinoussi Barre, F., and Wray, W. 1980. Vitamin C preferential toxicity for malignant melanoma cells. Nature 284: 629–631.PubMedCrossRefGoogle Scholar
  213. 212.
    Reynolds, C. P., Reynolds, D. A., Frenkel, E. P., and Smith, R. G. 1982. Selective toxicity of 6-hydroxydopamine and ascorbate for human neuroblastoma in vitro: A model for clearing marrow prior to autologous transplant. Cancer Res. 42: 1331–1336.PubMedGoogle Scholar
  214. 213.
    Benade, L., Howard, T., and Burk, D. 1969. Synergistic killing of Ehrlich ascites carcinoma cells by ascorbate and 3-amino-1,2,4-triazole. Oncology 23: 33–43.PubMedCrossRefGoogle Scholar
  215. 214.
    Kallistratos, G., and Fasske, E. 1979. Inhibition of benzopyrene carcinogenesis in rats with vitamin C. Folia Biochem. Biol. Graeca 16: 15–30.Google Scholar
  216. 215.
    Yamafuji, J., Nakamura, Y., Omura, H., Soeda, T., and Gyotoku, K. 1971. Anti-tumor potency of ascorbic, dehydroascorbic, or 2,3-diketogulonic acid and their action on deoxy-ribonucleic acid. A. Krebsforsch. Klin. Oncol. 21: 270–276.Google Scholar
  217. 216.
    Migliozzi, J. A. 1977. Effect of ascorbic acid on tumor growth. Br. J. Cancer 35: 448–453.PubMedCrossRefGoogle Scholar
  218. 217.
    Brunschwig, A. 1943. Vitamin C and tumor growth. Cancer Res. 3: 550–553.Google Scholar
  219. 218.
    Fodor, E., and Kunos. S. 1934. Die Wirkung der reinen ascorbinsure auf das Wachstum des experimentellen Mausecarcinomas. Krebsforsch 40: 567–571.CrossRefGoogle Scholar
  220. 219.
    Watson, A. F. 1943. The chemical reducing capacity and vitamin C content of transplantable tumors of the rat and guinea pig. Br. J. Exp. Pathol. 17: 124–134.Google Scholar
  221. 220.
    Kumar, M., and Axelrod, A. E. 1969. Circulating antibody formation in scorbutic guinea pigs. J. Nutr. 98: 41–44.PubMedGoogle Scholar
  222. 221.
    Kies, M. W., Mueller, S., and Alvord, E. C. 1964. Influence of ascorbic acid deficiency on immunologic mechanisms. Z. Immun. Allergie Forsch 126: 228–233.Google Scholar
  223. 222.
    Kalden, J. R., and Guthy, E. A. 1972. Prolonged skin allograft survival in vitamin C-deficient guinea-pigs. Eur. Surg. Res. 4: 114–119.PubMedCrossRefGoogle Scholar
  224. 223.
    Waddell, W. R., and Gerner, R. E. 1980. Indomethacin and ascorbate inhibit desmoid tumors. J. Surg. Oncol. 15: 85–90.PubMedCrossRefGoogle Scholar
  225. 224.
    Chlapowski, F. J., Kelly, L. A., and Butcher, R. W. 1975. Cyclic nucleotides in cultured cells. Adv. Cyclic Nucleotide Res. 6: 245–338.PubMedGoogle Scholar
  226. 225.
    Tewfik, F. A., Riley, E. F., and Mital, C. R. 1977. The influence of ascorbic acid on the growth of solid tumors in mice and on tumor control by X-irradiation. Radiat. Res. 70: 660.Google Scholar
  227. 226.
    Gruber, H. E., Tewfik, H. H., and Tewfik, F. A. 1980. Cytoarchitecture of Ehrlich ascites carcinoma implanted in the hind limb of ascorbic acid-supplemented mice. Eur. J. Cancer 16: 441–448.PubMedGoogle Scholar
  228. 227.
    O’Conner, M., Malone, J., Moriarty, M., and Mulgrew, S. 1977. A radioprotective effect of vitamin C observed in Chinese hamster ovary cells. Br. J. Radiol. 50: 587–591.CrossRefGoogle Scholar
  229. 228.
    Elvin, P., and Slater, T. F. 1981. Anti-tumor activity of novel adducts of ascorbic acid with aldehydes. Eur. J. Clin. Oncol. 17: 759–765.CrossRefGoogle Scholar
  230. 229.
    Kimoto, E., Tanaka, H., Gyotoku, J., Morishige, F., and Pauling, L. 1983. Enhancement of antitumor activity of ascorbate against Ehrlich ascites tumor cells by the copper-glycyglycyl-histidine complex. Cancer Res. 43: 824–828.PubMedGoogle Scholar
  231. 230.
    Yagishita, K., Takahashi, N., Yamamoto, H., Jinnouchi, H., Hiyoshi, S., and Miyakawa, T. 1976. Effects of tetraacetyl-bis-dehydroascorbic acid, a derivative of ascorbic acid, on Ehrlich cells and Hela cells (human carcinoma cells). J. Nutr. Sci. Vitaminol. 22: 419–427.PubMedCrossRefGoogle Scholar
  232. 231.
    Werner, B., Denzer, U., Mitschke, H., and Brassow, F. 1981. Vitamin C and Dunn-darmkrebs. Eine Experimentelle Studie. Langenbecks Arch. Chir. 354: 101–109.PubMedCrossRefGoogle Scholar
  233. 232.
    Reddy, B. S., Hirota, N., and Katayama, S. 1982. Effect of sodium ascorbate on 1,2-dimethylhydrazine-or methylnitrosourea-induced colon carcinogenesis in rats. Carcinogenesis 3: 1097–1099.PubMedCrossRefGoogle Scholar
  234. 233.
    Jacobs, M. M., and Griffin, A. C. 1979. Effects of selenium on chemical carcinogenesis: Comparative effects of antioxidants. Biol. Trace Elem. Res. 1: 1–13.CrossRefGoogle Scholar
  235. 234.
    Jones, F. E., Komorowski, R. A., and Condon, R. E. 1981. Chemoprevention of 1,2-dimethylhydrazine-induced large bowel neoplasms. Surg. Forum 32: 435–437.Google Scholar
  236. 235.
    Benedict, W. F., Wheatley, W. L., and Jones, P. A. 1980. Inhibition of chemically induced morphological transformation and reversion of the transformed phenotype by ascorbic acid in C3H/10T ½ cells. Cancer Res. 40: 2796–2801.PubMedGoogle Scholar
  237. 236.
    Gol-Winkler, R., DeClerck, Y., and Gielen, J. E. 1980. Ascorbic acid effect on methylcholanthrene-induced transformation in C3H10T ½ clone 8 cells. Toxicology 17: 237–239.PubMedCrossRefGoogle Scholar
  238. 237.
    Rosin, M. P., Peterson, A. R., and Stich, H. F. 1980. The effect on ascorbate on 3-methylcholanthrene-induced cell transformation in C3H 10T ½ mouse-embryo fibroblast cell cultures. Mutat. Res. 72: 533–537.PubMedGoogle Scholar
  239. 238.
    Sivak, A., and Tu, A. S. 1980. Cell culture tumor promotion experiments with saccharin, phorbol, myristate acetate and several common food materials. Cancer Lett. 10: 27–32PubMedCrossRefGoogle Scholar
  240. 239.
    Bainc, S. 1981. Vitamin C acts as a cocarcinogen to methylcholanthrene in guinea-pigs. Cancer Lett. 11: 239–242.CrossRefGoogle Scholar
  241. 240.
    Frith, C. H., Rule, J., and Kodell, R. L. 1980. The effects of ascorbic acid on the induction of urothelial lesions in mice by 2-acetylaminofluorene. Toxicology 6: 309–318.Google Scholar
  242. 241.
    Bruce, W. R., Varghese, A. J., Furrer, R., and Land, P. C. 1977. A mutagen in human feces. in H. H. Hiatt, J. D. Watson, and J. A. Winsten (Ed.) Origins of human cancer. pp. 1641–1644. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory.Google Scholar
  243. 242.
    Dion, P. W., Bright-See, E. B., Smith, C. C., and Bruce, W. R. 1982. The effect of dietary ascorbic acid or α-tocopherol on fecal mutagencity. Mutat. Res. 102: 27–37.PubMedCrossRefGoogle Scholar
  244. 243.
    Leuchtenberger, C., and Leuchtenberger, R. 1977. Protection of hamster lung cultures by l-cysteine or vitamin C against carcinogenic effects of fresh smoke from tobacco or marijuana cigarettes. Br. J. Exp. Pathol. 58: 625–633.PubMedGoogle Scholar
  245. 244.
    Leuchtenberger, C., Leuchtenberger, R., and Chapius, L. 1978. Difference in response to vitamin C between marijuana and tobacco smoke exposed human cell cultures. Adv. Biosci. 22/25: 209–218.Google Scholar
  246. 245.
    Seiler, J. P. 1977. Inhibition of testicular DNA synthesis by chemical mutagens and carcinogens. Preliminary results in the validation of a novel short term test. Mutat. Res. 46: 305–310.PubMedGoogle Scholar
  247. 246.
    Parshad, R., Sanford, K. K., Jones, G. M., and Tarone, R. E. 1978. Fluorescent light-induced chromosome damage and its prevention in mouse cells in culture. Proc. Natl. Acad. Sci. (USA) 75: 1830–1833.CrossRefGoogle Scholar
  248. 247.
    Shapiro, B., and Kollmann, G. 1969. Mechanism of protection of macromolecules against ionizing radiation by sulfhydryl and other protective agents. Radiat. Damage Sulphydryl Comp. Proc. Panel 23-43.Google Scholar
  249. 248.
    Clark, J. B. 1953. The effects of chemicals on the recombination rate in Bacterium coli. J. Gen. Microbiol. 8: 45–49.PubMedGoogle Scholar
  250. 249.
    Petrilli, F. L., and DeFlora, S. 1978. Metabolic deactivation of hexavalent chromium. Mutat. Res. 54: 139–147.PubMedGoogle Scholar
  251. 250.
    Khudoley, V., Malaveille, C., and Bartsch, H. 1981. Mutagenicity studies in Salmonella typhimurium on some carcinogenic N-nitramines in vitro and in the host-mediated assay in rats. Cancer Res. 41: 3205–3210.PubMedGoogle Scholar
  252. 251.
    Wirth, P. J., Dybing, E., vonBahr, C., and Thorgeirsson, S. 1980. Mechanism of N-hydroxyacetylarylamine mutagenicity in the Salmonella test system: Metabolic activation of N-hydroxyphenacetin by liver and kidney fractions from rat, mouse, hamster and man. Mol. Pharmacol. 18: 117–127.PubMedGoogle Scholar
  253. 252.
    Conger, B. V. 1975. Radioprotective effects of ascorbic acid in barley seeds. Radiat. Biol. 15: 39–48.CrossRefGoogle Scholar
  254. 253.
    Selimbekova, D. D. 1969. Radioprotective properties of ascorbic acid. Dokl. Akad. Nauk. Azerb. SSR 25: 78–80.Google Scholar
  255. 254.
    Lin, J. Y., Wang, H. I., and Yeh, Y. C. 1979. The mutagenicity of soy bean sauce. Food Cosmet. Toxicol. 17: 329–332.PubMedCrossRefGoogle Scholar
  256. 255.
    Munkres, K. D. 1979. Ageing of Neurospora crassa. VIII. Lethality and mutagenicity of ferrous ions, ascorbic acid, and malondialdehyde. Mech. Ageing Dev. 10: 249–260.PubMedCrossRefGoogle Scholar
  257. 256.
    Shamberger, R. J., Corlett, C. L., Beaman, K. D., and Kasten, B. L. 1979. Antioxidants reduce the mutagenic effect of malonaldehyde and β-propiolactone. Mutat. Res. 66: 349–355.PubMedCrossRefGoogle Scholar
  258. 257.
    Guttenplan, J. B. 1978. Mechanisms of inhibition by ascorbate of microbial mutagenesis induced by N-nitroso compounds. Cancer Res. 38: 2018–2022.PubMedGoogle Scholar
  259. 258.
    Kokatnur, M. G., Murray, M. L., and Correa, P. 1978. Mutagenic properties of nitrosated spermidine. Proc. Soc. Exp. Biol. Med. 158: 85–88.PubMedGoogle Scholar
  260. 259.
    DeFlora, S., and Picciott, A. 1980. Mutagenicity of cimetidine in nitrite-enriched human gastric juice. Carcinogenesis 1: 925–929.CrossRefGoogle Scholar
  261. 260.
    Neale, S., and Solt, A. K. 1981. The effect of ascorbic acid on the amine-nitrite and nitrosamine mutagenicity in bacteria injected into mice. Chem. Biol. Interact. 35: 199–205.PubMedCrossRefGoogle Scholar
  262. 261.
    Lee, K. Y., Choi, H. W., and Park, S. C. 1979. Bacterial mutation test for the detection of potential carcinogenicity of nitrite-treated Korean raw fishes. Korean J. Biochem. 11: 31–40.Google Scholar
  263. 262.
    Rao, B. G., MacDonald, I. A., and Hutchison, D. M. 1981. Nitrite-induced volatile mutagens from normal human feces. Cancer 47: 889–894.PubMedCrossRefGoogle Scholar
  264. 263.
    Rosin, M. P., San, R. H. C., and Stich, H. F. 1980. Mutagenic activity of ascorbate in mammalian cell cultures. Cancer Lett. 8: 299–305.PubMedCrossRefGoogle Scholar
  265. 264.
    Stich, H. F., Wei, L., and Whiting, R. F. 1979. The enhancing effect of transition metals on the chromosome-damaging action of ascorbate. Cancer Res. 39: 4145–4151.PubMedGoogle Scholar
  266. 265.
    Omura, H., Shinohara, K., Maeda, H., Nonaka, M., and Murakami, H. 1978. Mutagenic action of triose reductone and ascorbic acid on Salmonella typhimurium TA 100 strain. J. Nutr. Sci. Vitaminol. 24: 185–194.PubMedCrossRefGoogle Scholar
  267. 266.
    Stich, H. F., Wei, L., and Lam, P. 1978. The need for a mammalian test system for mutagens: Action of some reducing agents. Cancer Lett. 5: 199–204.PubMedCrossRefGoogle Scholar
  268. 267.
    Stich, H. F., Karim, J., Koropatnick, J., and Lo, L. 1976. Mutagenic action of ascorbic acid. Nature 260: 722–724.PubMedCrossRefGoogle Scholar
  269. 268.
    Macrae, W. D., and Stich, H. F. 1979. Induction of sister chromatid exchanges in Chinese hamster cells by the reducing agents bisulfite and ascorbic acid. Toxicology 13: 167–174.PubMedGoogle Scholar
  270. 269.
    Hayatsu, H., and Miura, A. 1970. The mutagenic action of sodium bisulfite. Biochem. Biophys. Res. Commun. 39: 156–160.PubMedCrossRefGoogle Scholar
  271. 270.
    Morgan, A. R., Cone, R. L., and Elgert, T. M. 1976. The mechanism of DNA strand breakage by vitamin C and superoxide and the protective roles of catalase and superoxide dismutase. Nucl. Acid Res. 3: 1139–1149.Google Scholar
  272. 271.
    Galloway, S. M., and Painter, R. B. 1979. Vitamin C is positive in the DNA synthesis inhibition and sister-chromatid exchange tests. Mutat. Res. 60: 321–327.PubMedGoogle Scholar
  273. 272.
    Speit, G., Wolf, M., and Vogel, W. 1980. The SCE-inducing capacity of vitamin C: Investigations in vitro and in vivo. Mutat. Res. 78: 273–278.PubMedCrossRefGoogle Scholar
  274. 273.
    Stich, H. F., Wei, L., and Whiting, R. F. 1980. Chromosome aberrations in mammalian cells exposed to vitamin C and multiple vitamin pills. Food Cosmet. Toxicol. 18: 497–501.PubMedCrossRefGoogle Scholar
  275. 274.
    Peterkofsky, B., and Prather, W. 1977. Cytotoxicity of ascorbate and other reducing agents toward cultured fibroblasts as a result of hydrogen peroxide formation. J. Cell Physiol. 90: 61–70.PubMedCrossRefGoogle Scholar
  276. 275.
    Andoh, T., and Ide, T. 1972. Disulfide bridges in proteins linking DNA in cultured mouse fibroblasts, strain Ŀ93. Exp. Cell Res. 74: 525–531.CrossRefGoogle Scholar
  277. 276.
    Ames, B., Durston, W., Yamaski, E., and Lee, P. 1973. Carcinogens are mutagens: A simple test system combining liver homogenates for activation and bacteria for detection. Proc. Natl. Acad. Sci. (USA) 70: 2281–2285.CrossRefGoogle Scholar
  278. 277.
    Andrews, L. S., Fysh, J. M., Hinson, J. A., and Gillette, J. R. 1979. Ascorbic acid inhibits covalent binding of enzymatically generated 2-acetyl-aminofluororene-N-sulfate to DNA under conditions in which it increases mutagenesis in Salmonella TA-1538. Life Sci. 24: 59–64.PubMedCrossRefGoogle Scholar
  279. 278.
    Sakai, S., Reinhold, C. E., Wirth, P. J., Thorgeirsson, P. J., and Snorri, S. 1978. Mechanism of in vitro mutagenic activation and covalent binding of N-hydroxy-2-acetylaminofluorene in isolated liver cell nuclei from rat and mouse. Cancer Res. 38: 2058–2067.PubMedGoogle Scholar
  280. 279.
    Schut, H. A. J., and Thorgeirsson, S. S. 1979. Mutagenic activation of N-hydroxy-2-acetylaminofluorene by developing epithelial cells of rat small intestine and effects of antioxidants. J. Natl. Cancer Inst. 63: 1405–1409.PubMedGoogle Scholar
  281. 280.
    Thorgeirsson, S. S., Sakai, S., and Wirth, P. J. 1980. Effect of ascorbic acid on in vitro mutagen covalent binding of N-hydroxyl-2-acetylaminofluorene in the rat. Mutat. Res. 70: 395–398.PubMedGoogle Scholar
  282. 281.
    Omura, H., Tomita, Y., Fujiki, H., Shinohara, K., and Murakami, H. 1978. Breaking action of reductones related to ascorbic acid on nucleic acids. J. Nutr. Sci. Vitaminol. 24: 263–270.PubMedCrossRefGoogle Scholar
  283. 282.
    Glatt, H. R., Oesch, F., and Neumann, H. G. 1980. Factors responsible for the metabolic formation and inactivation of bacterial mutagens from trans-4-acetylaminostilbene. Mutat. Res. 73: 237–250.PubMedGoogle Scholar
  284. 283.
    Omura, H., Iiyama, S., Tomita, Y., Narazaaki, Y., Shinohara, K., and Murakami, H. 1975. Breaking action of ascorbic acid on nucleic acids. J. Nutr. Sci. Vitaminol. 21: 237–249.PubMedCrossRefGoogle Scholar
  285. 284.
    Fomenko, L. A., Leonteva, G. A., Gaziev, A. I., and Kuzin, A. M. 1974. Radiosensitization of DNA in the radiosensitization on DNA in the presence of reducing agents and a catalyst of radical reactions. Radiobiology 14: 137–139.Google Scholar
  286. 285.
    Kuhnlein, U., Tsang, S. S., and Edwards, J. 1979. Characterization of DNA-damages by filtration through nitrocellulose filters: A simple probe for DNA-modifying agents. Mutat. Res. 64: 167–182.PubMedGoogle Scholar
  287. 286.
    Smith, H. W. 1953. The effect of physical and chemical changes on the liberation of phage particles by lysogenic strains of Salmonella. J. Gen. Microbiol. 8: 116–134.PubMedGoogle Scholar
  288. 287.
    Murata, A., Kitagawa, K., and Saruno, R. 1971. Inactivation of bacteriophages by ascorbic acid. Agr. Biol. Chem. 35: 294–296.CrossRefGoogle Scholar
  289. 288.
    Murata, A., and Kitagawa, K. 1973. Mechanism of inactivation of bacteriophage J1 by ascorbic acid. Agr. Biol. Chem. 37: 1145–1151.CrossRefGoogle Scholar
  290. 289.
    Murata, A., Kitagawa, K., Inmaru, H., and Saruno, R. 1972. Inactivation of single-stranded DNA and RNA phages by ascorbic acids and thiol reducing agents. Agr. Biol. Chem. 36: 2591–2599.Google Scholar
  291. 290.
    Murata, A., Oyadomari, R., Dhashi, T., and Kitagawa, K. 1975. Mechanism of inactivation of bacteriophage δA containing single-stranded DNA by ascorbic acid. J. Nutr. Sci. Vitaminol. 21: 261–269.PubMedCrossRefGoogle Scholar
  292. 291.
    Wong, K., Morgan, A. R., and Paranchych, W. 1974. Controlled cleavage of phage R17 RNA within the virion by treatment with ascorbate and copper (11). Can. J. Biochem. 52: 950–958.PubMedCrossRefGoogle Scholar
  293. 292.
    Bode, V. C. 1967. Single-strand scissions in circular and linear γ DNA by the presence of dithiothreitol and other reducing agents. J. Mol. Biol. 26: 125–129.PubMedCrossRefGoogle Scholar
  294. 293.
    McCarty, M. 1945. Reversible inactivation of the substance inducing transformation of pneumococcal types. J. Exp. Med. 81: 507–514.CrossRefGoogle Scholar
  295. 294.
    Kenyon, A., and Andress, L. 1980. Does vitamin C induce X-linked recessive lethal mutations in Drosophilia melanogaster? Genetics 94: 552–553.Google Scholar
  296. 295.
    Kalus, W. H., Filby, W. G., and Munzner, R. 1982. Chemical aspects of the mutagenic activity of the ascorbic acid autoxidation system. Z. Naturforsch. 37: 40–45.Google Scholar
  297. 296.
    Murphy, L. C., Wild, J., Posen, S., and Stone, G. 1979. 25-Hydroxycholecalciferol receptors in human breast cancer. Br. J. Cancer 39: 531–535.PubMedCrossRefGoogle Scholar
  298. 297.
    Eisman, J. A., MacIntyre, I., Martin, T. J., and Moseley, J. M. 1979. 1,25-Dihydroxy vitamin D receptor in breast cancer cells. Lancet 2: 1335–1336.PubMedCrossRefGoogle Scholar
  299. 298.
    Colston, K. W., Colston, M. J., and Feldman, D. 1981. 1,25-Dihydroxy vitamin D3 and malignant melanoma: The presence of receptors and inhibition of cell growth in culture. Endocrinology 108: 1083–1086.PubMedCrossRefGoogle Scholar
  300. 299.
    Colston, K., Colston, M. J., Fieldsteel, A. H., and Feldman, D. 1982. 1,25-Dihydroxy vitamin D3 receptors in human epithelial cancer cell lines. Cancer Res. 42: 856–859.PubMedGoogle Scholar
  301. 300.
    Shamberger, R. J. 1970. Relationships of selenium to Cancer. I. Inhibitory effect of selenium on carcinogenesis. J. Natl. Cancer Inst. 44: 931–936.PubMedGoogle Scholar
  302. 301.
    Jaffe, W. 1949. The influence of wheatgerm oil on the production of tumors in rats by methylcholanthrene. Exp. Med. Surg. 4: 278–282.Google Scholar
  303. 302.
    Haddow, A., and Russell, H. 1937. The influence of wheat germ oil in the diet on the induction of tumors in mice. Am. J. Cancer 29: 363–366.Google Scholar
  304. 303.
    Epstein, S. S., Joshi, S., Andrea, J., Forsyth, J., and Mantal, N. 1967. The null effect of antioxidants on the carcinogenicity of 3,4,9,10-dibenzpyrene to mice. Life Sci. 6: 225–233.PubMedCrossRefGoogle Scholar
  305. 304.
    Haber, S. L., and Wissler, R. W. 1962. Effect of vitamin E on carcinogenicity on methylcholanthrene. Proc. Soc. Exp. Biol. Med. III: 774–775.Google Scholar
  306. 305.
    Harman, D. 1969. Dibenzanthracene induced cancer. Inhibiting effect of vitamin E. Clin Res. 17: 125.Google Scholar
  307. 306.
    Ip, C. 1982. Dietary vitamin E intake and mammary carcinogenesis in rats. Carcinogenesis 3: 1453–1456.PubMedCrossRefGoogle Scholar
  308. 307.
    Narayan, K. A. 1970. Vitamin E deficiency and chemical carcinogenesis. Experientia 26: 840–841.PubMedCrossRefGoogle Scholar
  309. 308.
    Konings, A. W. T., and Trieling, W. B. 1977. The inhibition of DNA synthesis in vitamin E-depleted lymphosarcoma cells by x-rays and cytostatics. Int. J. Radiat Biol. 31: 397–400.CrossRefGoogle Scholar
  310. 309.
    Shklar, G. 1982. Oral mucosal carcinogenesis in hamsters: Inhibition by vitamin E. J. Natl. Cancer Inst. 68: 791–797.PubMedGoogle Scholar
  311. 310.
    Pauling, L., Willoughby, R., Reymonds, R., Blaisdell, B. E., and Lawson, S. 1982. Incidence of squamous cell carcinoma in hairless mice irradiated with ultraviolet light in relation to intake of ascorbic acid and of D, L. α-tocopheryl acetate. Int. J. Vitam. Nutr. Res. Suppl. 79: 53–82.Google Scholar
  312. 311.
    Weisburger, J. H., Reddy, D. V. M., Hill, P., Cohen, L. A., Wynder, E. L., and Spingarn, N. E. 1980. Nutrition and cancer-on the mechanisms bearing on causes of cancer of the colon, breast, prostate and stomach. Bull N.Y. Acad. Med. 56: 673–696.PubMedGoogle Scholar
  313. 312.
    Shamberger, R. J., Baughman, F. F., Kalchert, S. S., and Willis, C. E. 1973. Carcinogen-induced chromosomal breakage decreased by antioxidants. Proc. Natl. Acad. Sci. (USA) 70: 1461–1467.CrossRefGoogle Scholar
  314. 313.
    Smalls, E., and Patterson, R. M. 1982. Reduction of benzopyrene induced chromosomal aberrations by dl-alpha-tocopherol. Eur. J. Cell Biol. 28: 92–97.PubMedGoogle Scholar
  315. 314.
    Dion, P. W., Bright-See, E. B., Smith, C. C., and Bruce, W. R. 1982. The effect of dietary ascorbic acid and α-tocopherol on fecal mutagenicity. Mutat. Res. 102: 27–37.PubMedCrossRefGoogle Scholar
  316. 315.
    Abrams, A. A. 1965. Use of vitamin E. in chronic mastitis. N. Engl. J. Med. 272: 1081–1082.Google Scholar
  317. 316.
    London, R. S., Solomon, D. M., London, E. D., Strummer, D., Bankowski, J., and Mair, P. P. 1978. Mammary Dysplasia; clinical response and urinary excretion of 11-deoxyketosteroids and pregnanediol following a-tocopherol therapy. Breast 4: 19–22.Google Scholar
  318. 317.
    Hilgard, P., and Thornes, R. D. 1976. Anticoagulants in the treatment of cancer. Eur. J. Cancer 12: 755–762.Google Scholar
  319. 318.
    Hilgard, P., Schultz, H., Wetzig, G., Schmitt, and Schmidt, C. G. 1977. Oral anticoagulation in the treatment of a spontaneously metastasizing murine tumor (3LL). Br. J. Cancer 35: 448–453.CrossRefGoogle Scholar
  320. 319.
    Hilgard, P. 1977. Experimental vitamin K deficiency and spontaneous metastases. Br. J. Cancer 35: 448–453.CrossRefGoogle Scholar
  321. 320.
    Israels, L. G., Oilman, D. J., Friesen, E., and Israels, E. D. 1982. Vitamin K as a regulator of benzopyrene metabolism, mutagenesis and carcinogenesis. Clin. Invest. Med. 5: 46B.Google Scholar

Copyright information

© Raymond J. Shamberger 1984

Authors and Affiliations

  • Raymond J. Shamberger
    • 1
  1. 1.The Cleveland Clinic FoundationClevelandUSA

Personalised recommendations