Vitamin C, vitamin E, and βcarotene in cancer Chemoprevention

Phytopharmaceuticals in Cancer Chemoprevention

Volumn , Issue , 2004, Pages 271-310

  Higdon, Jane ^a   Frei, Balz ^a  

^a OREGON STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 25444491719     PISSN: None     EISSN: None     Source Type: Book    
DOI: None     Document Type: Chapter

References (264)

1. Block, G., Patterson, B., and Subar, A., Fruit, vegetables, and cancer prevention: a review of the epidemiological evidence, Nutr. Cancer, 18, 1, 1992.
2. Steinmetz, K.A. and Potter, J.D., Vegetables, fruit, and cancer prevention: a review, J. Am. Diet. Assoc., 96, 1027, 1996.
3. Peto, R., Doll, R., Buckley, J.D., and Sporn, M.B., Can dietary beta-carotene materially reduce human cancer rates?, Nature, 290, 201, 1981.
4. Blot, W.J., Li, J.Y., Taylor, P.R., Guo, W., Dawsey, S., Wang, G.Q., Yang, C.S., Zheng, S.F., Gail, M., Li, G.Y. et al., Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population, J. Natl. Cancer Inst., 85, 1483, 1993.
5. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group, The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers, New England J. Med., 330, 1029, 1994.
6. Omenn, G.S., Goodman, G.E., Thornquist, M.D., Balmes, J., Cullen, M.R., Glass, A., Keogh, J.P., Meyskens, F.L., Valanis, B., Williams, J.H., Barnhart, S., and Hammar, S., Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease, New England J. Med., 334, 1150, 1996.
7. Levine, M., Rumsey, S.C., Daruwala, R., Park, J.B., and Wang, Y., Criteria and recommendations for vitamin C intake, JAMA, 281, 1415, 1999.
8. Levine, M., Conry-Cantilena, C., Wang, Y., Welch, R.W., Washko, P.W., Dhariwal, K.R., Park, J.B., Lazarev, A., Graumlich, J.F., King, J., and Cantilena, L.R., Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance, Proc. Natl. Acad. Sci. USA, 93, 3704, 1996.
9. Carr, A.C. and Frei, B., Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans, Am. J. Clin. Nutr., 69, 1086, 1999.
10. Food and Nutrition Board, Institute of Medicine, Vitamin C, in Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids, National Academy Press, Washington, DC, 2000, pp. 95.
11. Upston, J.M., Terentis, A.C., and Stocker, R., Tocopherol-mediated peroxidation of lipoproteins:implications for vitamin E as a potential antiatherogenic supplement, FASEB J., 13, 977, 1999.
12. Traber, M.G., Vitamin E, in Nutrition in Health and Disease, 9th ed., Shils, M., Olson, J.A., Shike, M., and Ross, A.C., Eds., Williams & Wilkins, Baltimore, 1999, p. 347.
13. Kiyose, C., Muramatsu, R., Kameyama, Y., Ueda, T., and Igarashi, O., Biodiscrimination of alphatocopherol stereoisomers in humans after oral administration, Am. J. Clin. Nutr., 65, 785, 1997.
14. Food and Nutrition Board, Institute of Medicine, Vitamin E, in Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids, National Academy Press, Washington, DC, 2000, pp. 95.
15. Halliwell, B. and Gutteridge, J.M.C., Free Radicals in Biology and Medicine, 3rd ed., Oxford University Press, New York, 1999.
16. Buettner, G.R., The pecking order of free radicals and antioxidants: lipid peroxidation, alphatocopherol, and ascorbate, Arch. Biochem. Biophys., 300, 535, 1993.
17. Brigelius-Flohe, R., Kelly, F.J., Salonen, J.T., Neuzil, J., Zingg, J.M., and Azzi, A., The European perspective on vitamin E: current knowledge and future research, Am. J. Clin. Nutr., 76, 703, 2002.
18. Behrens, W.A. and Madere, R., Alpha- and gamma-tocopherol concentrations in human serum, J. Am. Coll. Nutr., 5, 91, 1986.
19. Jiang, Q., Lykkesfeldt, J., Shigenaga, M.K., Shigeno, E.T., Christen, S., and Ames, B.N., Gammatocopherol supplementation inhibits protein nitration and ascorbate oxidation in rats with inflammation, Free Radic. Biol. Med., 33, 1534, 2002.
20. Jiang, Q., Christen, S., Shigenaga, M.K., and Ames, B.N., Gamma-tocopherol, the major form of vitamin E in the US diet, deserves more attention, Am. J. Clin. Nutr., 74, 714, 2001.
21. Solomons, N.W., Vitamin A and carotenoids, in Present Knowledge in Nutrition, 8th ed., Bowman, B.A. and Russell, R.M., Eds., ILSI Press, Washington, DC, 2001, p. 127.
22. Food and Nutrition Board, Institute of Medicine, Beta-carotene and other carotenoids, in Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids, National Academy Press, Washington, DC, 2000, pp. 325.
23. Burton, G.W. and Ingold, K.U., Beta-carotene: an unusual type of lipid antioxidant, Science, 224, 569, 1984.
24. Krinsky, N.I., The antioxidant and biological properties of the carotenoids, Ann. N.Y. Acad. Sci., 854, 443, 1998.
25. Hatta, A. and Frei, B., Oxidative modification and antioxidant protection of human low density lipoprotein at high and low oxygen partial pressures, J. Lipid Res., 36, 2383, 1995.
26. Liebler, D.C., Stratton, S.P., and Kaysen, K.L., Antioxidant actions of beta-carotene in liposomal and microsomal membranes: role of carotenoid-membrane incorporation and alpha-tocopherol, Arch. Biochem. Biophys., 338, 244, 1997.
27. Allard, J.P., Royall, D., Kurian, R., Muggli, R., and Jeejeebhoy, K.N., Effects of beta-carotene supplementation on lipid peroxidation in humans, Am. J. Clin. Nutr., 59, 884, 1994.
28. Winklhofer-Roob, B.M., Puhl, H., Khoschsorur, G., van’t Hof, M.A., Esterbauer, H., and Shmerling, D.H., Enhanced resistance to oxidation of low density lipoproteins and decreased lipid peroxide formation during beta-carotene supplementation in cystic fibrosis, Free Radic. Biol. Med., 18, 849, 1995.
29. Pryor, W.A., Stahl, W., and Rock, C.L., Beta carotene: from biochemistry to clinical trials, Nutr. Rev., 58, 39, 2000.
30. Woodall, A.A. and Ames, B.N., Diet and oxidative damage to DNA: the importance of ascorbate as an antioxidant, in Vitamin C in Health and Disease, Packer, L. and Fuchs, J., Eds., Marcel Dekker, New York, 1997, pp. 193.
31. Wiseman, H. and Halliwell, B., Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer, Biochem. J., 313 (Pt. 1), 17, 1996.
32. Ames, B.N., Shigenaga, M.K., and Hagen, T.M., Oxidants, antioxidants, and the degenerative diseases of aging, Proc. Natl. Acad. Sci. USA, 90, 7915, 1993.
33. Collins, A.R., Oxidative DNA damage, antioxidants, and cancer, Bioessays, 21, 238, 1999.
34. Halliwell, B., Vitamin C and genomic stability, Mutat. Res., 475, 29, 2001.
35. Asami, S., Manabe, H., Miyake, J., Tsurudome, Y., Hirano, T., Yamaguchi, R., Itoh, H., and Kasai, H., Cigarette smoking induces an increase in oxidative DNA damage, 8-hydroxydeoxyguanosine, in a central site of the human lung, Carcinogenesis, 18, 1763, 1997.
36. Poulsen, H.E., Loft, S., Prieme, H., Vistisen, K., Lykkesfeldt, J., Nyyssonen, K., and Salonen, J.T., Oxidative DNA damage in vivo: relationship to age, plasma antioxidants, drug metabolism, glutathione-S-transferase activity and urinary creatinine excretion, Free Radic. Res., 29, 565, 1998.
37. Halliwell, B., Can oxidative DNA damage be used as a biomarker of cancer risk in humans? Problems, resolutions and preliminary results from nutritional supplementation studies, Free Radic. Res., 29, 469, 1998.
38. Loft, S. and Poulsen, H.E., Antioxidant intervention studies related to DNA damage, DNA repair and gene expression, Free Radic. Res., 33 Suppl., S67, 2000.
39. Loft, S., Deng, X.S., Tuo, J., Wellejus, A., Sorensen, M., and Poulsen, H.E., Experimental study of oxidative DNA damage, Free Radic. Res., 29, 525, 1998.
40. Cooke, M.S., Lunec, J., and Evans, M.D., Progress in the analysis of urinary oxidative DNA damage, Free Radic. Biol. Med., 33, 1601, 2002.
41. Lenton, K.J., Therriault, H., Fulop, T., Payette, H., and Wagner, J.R., Glutathione and ascorbate are negatively correlated with oxidative DNA damage in human lymphocytes, Carcinogenesis, 20, 607, 1999.
42. Bianchini, F., Elmstahl, S., Martinez-Garcia, C., van Kappel, A.L., Douki, T., Cadet, J., Ohshima, H., Riboli, E., and Kaaks, R., Oxidative DNA damage in human lymphocytes: correlations with plasma levels of alpha-tocopherol and carotenoids, Carcinogenesis, 21, 321, 2000.
43. Fraga, C.G., Motchnik, P.A., Shigenaga, M.K., Helbock, H.J., Jacob, R.A., and Ames, B.N., Ascorbic acid protects against endogenous oxidative DNA damage in human sperm, Proc. Natl. Acad. Sci. USA, 88, 11003, 1991.
44. Daube, H., Scherer, G., Riedel, K., Ruppert, T., Tricker, A.R., Rosenbaum, P., and Adlkofer, F., DNA adducts in human placenta in relation to tobacco smoke exposure and plasma antioxidant status, J. Cancer Res. Clin. Oncol., 123, 141, 1997.
45. Collins, A.R., Olmedilla, B., Southon, S., Granado, F., and Duthie, S.J., Serum carotenoids and oxidative DNA damage in human lymphocytes, Carcinogenesis, 19, 2159, 1998.
46. Loft, S., Vistisen, K., Ewertz, M., Tjonneland, A., Overvad, K., and Poulsen, H.E., Oxidative DNA damage estimated by 8-hydroxydeoxyguanosine excretion in humans: influence of smoking, gender and body mass index, Carcinogenesis, 13, 2241, 1992.
47. Huang, H.Y., Helzlsouer, K.J., and Appel, L.J., The effects of vitamin C and vitamin E on oxidative DNA damage: results from a randomized controlled trial, Cancer Epidemiol. Biomarkers Prev., 9, 647, 2000.
48. Kristenson, M., Kucinskiene, Z., Schafer-Elinder, L., Leanderson, P., and Tagesson, C., The LiVicordia study: lower serum levels of beta-carotene in Lithuanian men are accompanied by higher urinary excretion of the oxidative DNA adduct, 8-hydroxydeoxyguanosine, Nutrition, 19, 11, 2003.
49. Lee, B.M., Lee, S.K., and Kim, H.S., Inhibition of oxidative DNA damage, 8-OHdG, and carbonyl contents in smokers treated with antioxidants (vitamin E, vitamin C, beta-carotene and red ginseng), Cancer Lett., 132, 219, 1998.
50. Welch, R.W., Turley, E., Sweetman, S.F., Kennedy, G., Collins, A.R., Dunne, A., Livingstone, M.B., McKenna, P.G., McKelvey-Martin, V.J., and Strain, J.J., Dietary antioxidant supplementation and DNA damage in smokers and nonsmokers, Nutr. Cancer, 34, 167, 1999.
51. Howard, D.J., Ota, R.B., Briggs, L.A., Hampton, M., and Pritsos, C.A., Oxidative stress induced by environmental tobacco smoke in the workplace is mitigated by antioxidant supplementation, Cancer Epidemiol. Biomarkers Prev., 7, 981, 1998.
52. Jacobson, J.S., Begg, M.D., Wang, L.W., Wang, Q., Agarwal, M., Norkus, E., Singh, V.N., Young, T.L., Yang, D., and Santella, R.M., Effects of a 6-month vitamin intervention on DNA damage in heavy smokers, Cancer Epidemiol. Biomarkers Prev., 9, 1303, 2000.
53. Vojdani, A., Bazargan, M., Vojdani, E., and Wright, J., New evidence for antioxidant properties of vitamin C, Cancer Detect. Prev., 24, 508, 2000.
54. Cooke, M.S., Evans, M.D., Podmore, I.D., Herbert, K.E., Mistry, N., Mistry, P., Hickenbotham, P.T., Hussieni, A., Griffiths, H.R., and Lunec, J., Novel repair action of vitamin C upon in vivo oxidative DNA damage, FEBS Lett., 439, 363, 1998.
55. Podmore, I.D., Griffiths, H.R., Herbert, K.E., Mistry, N., Mistry, P., and Lunec, J., Vitamin C exhibits pro-oxidant properties, Nature, 392, 559, 1998.
56. Rehman, A., Collis, C.S., Yang, M., Kelly, M., Diplock, A.T., Halliwell, B., and Rice-Evans, C., The effects of iron and vitamin C co-supplementation on oxidative damage to DNA in healthy volunteers, Biochem. Biophys. Res. Commun., 246, 293, 1998.
57. Proteggente, A.R., Rehman, A., Halliwell, B., and Rice-Evans, C.A., Potential problems of ascorbate and iron supplementation: pro-oxidant effect in vivo?, Biochem. Biophys. Res. Commun., 277, 535, 2000.
58. Prieme, H., Loft, S., Nyyssonen, K., Salonen, J.T., and Poulsen, H.E., No effect of supplementation with vitamin E, ascorbic acid, or coenzyme Q10 on oxidative DNA damage estimated by 8-oxo-7,8- dihydro-2'-deoxyguanosine excretion in smokers, Am. J. Clin. Nutr., 65, 503, 1997.
59. Porkkala-Sarataho, E., Salonen, J.T., Nyyssonen, K., Kaikkonen, J., Salonen, R., Ristonmaa, U., Diczfalusy, U., Brigelius-Flohe, R., Loft, S., and Poulsen, H.E., Long-term effects of vitamin E, vitamin C, and combined supplementation on urinary 7-hydro-8-oxo-2'-deoxyguanosine, serum cholesterol oxidation products, and oxidation resistance of lipids in nondepleted men, Arterioscler. Thromb. Vasc. Biol., 20, 2087, 2000.
60. van Poppel, G., Poulsen, H., Loft, S., and Verhagen, H., No influence of beta carotene on oxidative DNA damage in male smokers, J. Natl. Cancer Inst., 87, 310, 1995.
61. Sumida, S., Doi, T., Sakurai, M., Yoshioka, Y., and Okamura, K., Effect of a single bout of exercise and beta-carotene supplementation on the urinary excretion of 8-hydroxy-deoxyguanosine in humans, Free Radic. Res., 27, 607, 1997.
62. Witt, E.H., Reznick, A.Z., Viguie, C.A., Starke-Reed, P., and Packer, L., Exercise, oxidative damage and effects of antioxidant manipulation, J. Nutr., 122, 766, 1992.
63. Green, M.H., Lowe, J.E., Waugh, A.P., Aldridge, K.E., Cole, J., and Arlett, C.F., Effect of diet and vitamin C on DNA strand breakage in freshly isolated human white blood cells, Mutat. Res., 316, 91, 1994.
64. Panayiotidis, M. and Collins, A.R., Ex vivo assessment of lymphocyte antioxidant status using the Comet assay, Free Radic. Res., 27, 533, 1997.
65. Brennan, L.A., Morris, G.M., Wasson, G.R., Hannigan, B.M., and Barnett, Y.A., The effect of vitamin C or vitamin E supplementation on basal and H2O2-induced DNA damage in human lymphocytes, Br. J. Nutr., 84, 195, 2000.
66. Duthie, S.J., Ma, A., Ross, M.A., and Collins, A.R., Antioxidant supplementation decreases oxidative DNA damage in human lymphocytes, Cancer Res., 56, 1291, 1996.
67. Anderson, D., Phillips, B.J., Yu, T.W., Edwards, A.J., Ayesh, R., and Butterworth, K.R., The effects of vitamin C supplementation on biomarkers of oxygen radical generated damage in human volunteers with “low” or “high” cholesterol levels, Environ. Mol. Mutagen., 30, 161, 1997.
68. Astley, S., Langrish-Smith, A., Southon, S., and Sampson, M., Vitamin E supplementation and oxidative damage to DNA and plasma LDL in type 1 diabetes, Diabetes Care, 22, 1626, 1999.
69. White, K.L., Chalmers, D.M., Martin, I.G., Everett, S.M., Neville, P.M., Naylor, G., Sutcliffe, A.E., Dixon, M.F., Turner, P.C., and Schorah, C.J., Dietary antioxidants and DNA damage in patients on long-term acid-suppression therapy: a randomized controlled study, Br. J. Nutr., 88, 265, 2002.
70. Jenkinson, A.M., Collins, A.R., Duthie, S.J., Wahle, K.W., and Duthie, G.G., The effect of increased intakes of polyunsaturated fatty acids and vitamin E on DNA damage in human lymphocytes, FASEB J., 13, 2138, 1999.
71. Pool-Zobel, B.L., Bub, A., Muller, H., Wollowski, I., and Rechkemmer, G., Consumption of vegetables reduces genetic damage in humans: first results of a human intervention trial with carotenoid-rich foods, Carcinogenesis, 18, 1847, 1997.
72. Hecht, S.S., Approaches to cancer prevention based on an understanding of N-nitrosamine carcinogenesis, Proc. Soc. Exp. Biol. Med., 216, 181, 1997.
73. Mirvish, S.S., Role of N-nitroso compounds (NOC) and N-nitrosation in etiology of gastric, esophageal, nasopharyngeal and bladder cancer and contribution to cancer of known exposures to NOC, Cancer Lett., 93, 17, 1995.
74. Tannenbaum, S.R., Wishnok, J.S., and Leaf, C.D., Inhibition of nitrosamine formation by ascorbic acid, Am. J. Clin. Nutr., 53, 247S, 1991.
75. Mannick, E.E., Bravo, L.E., Zarama, G., Realpe, J.L., Zhang, X.J., Ruiz, B., Fontham, E.T., Mera, R., Miller, M.J., and Correa, P., Inducible nitric oxide synthase, nitrotyrosine, and apoptosis in Helicobacter pylori gastritis: effect of antibiotics and antioxidants, Cancer Res., 56, 3238, 1996.
76. Leaf, C.D., Vecchio, A.J., Roe, D.A., and Hotchkiss, J.H., Influence of ascorbic acid dose on N-nitrosoproline formation in humans, Carcinogenesis, 8, 791, 1987.
77. Mirvish, S.S., Grandjean, A.C., Reimers, K.J., Connelly, B.J., Chen, S.C., Morris, C.R., Wang, X., Haorah, J., and Lyden, E.R., Effect of ascorbic acid dose taken with a meal on nitrosoproline excretion in subjects ingesting nitrate and proline, Nutr. Cancer, 31, 106, 1998.
78. Mirvish, S.S., Effects of vitamins C and E on N-nitroso compound formation, carcinogenesis, and cancer, Cancer, 58, 1842, 1986.
79. Reed, J.C., Dysregulation of apoptosis in cancer, J. Clin. Oncol., 17, 2941, 1999.
80. Lavrovsky, Y., Chatterjee, B., Clark, R.A., and Roy, A.K., Role of redox-regulated transcription factors in inflammation, aging and age-related diseases, Exp. Gerontol., 35, 521, 2000.
81. Bijur, G.N., Briggs, B., Hitchcock, C.L., and Williams, M.V., Ascorbic acid-dehydroascorbate induces cell cycle arrest at G2/M DNA damage checkpoint during oxidative stress, Environ. Mol. Mutagen., 33, 144, 1999.
82. Reddy, V.G., Khanna, N., and Singh, N., Vitamin C augments chemotherapeutic response of cervical carcinoma HeLa cells by stabilizing P53, Biochem. Biophys. Res. Commun., 282, 409, 2001.
83. Peltomaki, P., Deficient DNA mismatch repair: a common etiologic factor for colon cancer, Hum. Mol. Genet., 10, 735, 2001.
84. Catani, M.V., Costanzo, A., Savini, I., Levrero, M., de Laurenzi, V., Wang, J.Y., Melino, G., and Avigliano, L., Ascorbate up-regulates MLH1 (Mut L homologue-1) and p73: implications for the cellular response to DNA damage, Biochem. J., 364, 441, 2002.
85. Gopalakrishna, R. and Jaken, S., Protein kinase C signaling and oxidative stress, Free Radic. Biol. Med., 28, 1349, 2000.
86. Azzi, A., Breyer, I., Feher, M., Ricciarelli, R., Stocker, A., Zimmer, S., and Zingg, J., Nonantioxidant functions of alpha-tocopherol in smooth muscle cells, J. Nutr., 131, 378S, 2001.
87. Tasinato, A., Boscoboinik, D., Bartoli, G.M., Maroni, P., and Azzi, A., d-Alpha-tocopherol inhibition of vascular smooth muscle cell proliferation occurs at physiological concentrations, correlates with protein kinase C inhibition, and is independent of its antioxidant properties, Proc. Natl. Acad. Sci. USA, 92, 12190, 1995.
88. Clement, S., Tasinato, A., Boscoboinik, D., and Azzi, A., The effect of alpha-tocopherol on the synthesis, phosphorylation and activity of protein kinase C in smooth muscle cells after phorbol 12-myristate 13-acetate down-regulation, Eur. J. Biochem., 246, 745, 1997.
89. Ricciarelli, R., Tasinato, A., Clement, S., Ozer, N.K., Boscoboinik, D., and Azzi, A., alpha-Tocopherol specifically inactivates cellular protein kinase C alpha by changing its phosphorylation state, Biochem. J., 334 (Pt. 1), 243, 1998.
90. Neuzil, J., Weber, T., Schroder, A., Lu, M., Ostermann, G., Gellert, N., Mayne, G.C., Olejnicka, B., Negre-Salvayre, A., Sticha, M., Coffey, R.J., and Weber, C., Induction of cancer cell apoptosis by alpha-tocopheryl succinate: molecular pathways and structural requirements, FASEB J., 15, 403, 2001.
91. Bertram, J.S., Carotenoids and gene regulation, Nutr. Rev., 57, 182, 1999.
92. Cooper, D.A., Eldridge, A.L., and Peters, J.C., Dietary carotenoids and lung cancer: a review of recent research, Nutr. Rev., 57, 133, 1999.
93. Stahl, W., Nicolai, S., Briviba, K., Hanusch, M., Broszeit, G., Peters, M., Martin, H.D., and Sies, H., Biological activities of natural and synthetic carotenoids: induction of gap junctional communication and singlet oxygen quenching, Carcinogenesis, 18, 89, 1997.
94. Banoub, R.W., Fernstrom, M., and Ruch, R.J., Lack of growth inhibition or enhancement of gap junctional intercellular communication and connexin43 expression by beta-carotene in murine lung epithelial cells in vitro, Cancer Lett., 108, 35, 1996.
95. Krutovskikh, V., Asamoto, M., Takasuka, N., Murakoshi, M., Nishino, H., and Tsuda, H., Differential dose-dependent effects of alpha-, beta-carotenes and lycopene on gap-junctional intercellular communication in rat liver in vivo, Jpn. J. Cancer Res., 88, 1121, 1997.
96. World Cancer Research Fund, Food, Nutrition, and the Prevention of Cancer: a global perspective, American Institute for Cancer Research, Washington, DC, 1997.
97. Dunn, G.P., Bruce, A.T., Ikeda, H., Old, L.J., and Schreiber, R.D., Cancer immunoediting: from immunosurveillance to tumor escape, Nat. Immunol., 3, 991, 2002.
98. Del Rio, M., Ruedas, G., Medina, S., Victor, V.M., and De la Fuente, M., Improvement by several antioxidants of macrophage function in vitro, Life Sci., 63, 871, 1998.
99. Campbell, J.D., Cole, M., Bunditrutavorn, B., and Vella, A.T., Ascorbic acid is a potent inhibitor of various forms of T cell apoptosis, Cell. Immunol., 194, 1, 1999.
100. Radoja, S. and Frey, A.B., Cancer-induced defective cytotoxic T lymphocyte effector function: another mechanism how antigenic tumors escape immune-mediated killing, Mol. Med., 6, 465, 2000.
101. O’Connell, J., Bennett, M.W., Nally, K., Houston, A., O’Sullivan, G.C., and Shanahan, F., Altered mechanisms of apoptosis in colon cancer: Fas resistance and counterattack in the tumor-immune conflict, Ann. N. Y. Acad. Sci., 910, 178, 2000.
102. Jacob, R.A., Kelley, D.S., Pianalto, F.S., Swendseid, M.E., Henning, S.M., Zhang, J.Z., Ames, B.N., Fraga, C.G., and Peters, J.H., Immunocompetence and oxidant defense during ascorbate depletion of healthy men, Am. J. Clin. Nutr., 54, 1302S, 1991.
103. Anderson, R., Oosthuizen, R., Maritz, R., Theron, A., and Van Rensburg, A.J., The effects of increasing weekly doses of ascorbate on certain cellular and humoral immune functions in normal volunteers, Am. J. Clin. Nutr., 33, 71, 1980.
104. Panush, R.S., Delafuente, J.C., Katz, P., and Johnson, J., Modulation of certain immunologic responses by vitamin C, III: potentiation of in vitro and in vivo lymphocyte responses, Int. J. Vitam. Nutr. Res. Suppl., 23, 35, 1982.
105. Heuser, G. and Vojdani, A., Enhancement of natural killer cell activity and T and B cell function by buffered vitamin C in patients exposed to toxic chemicals: the role of protein kinase-C, Immunopharmacol. Immunotoxicol., 19, 291, 1997.
106. Han, S.N. and Meydani, S.N., Antioxidants, cytokines, and influenza infection in aged mice and elderly humans, J. Infect. Dis., 182 (Suppl. 1), S74, 2000.
107. Meydani, S.N., Barklund, M.P., Liu, S., Meydani, M., Miller, R.A., Cannon, J.G., Morrow, F.D., Rocklin, R., and Blumberg, J.B., Vitamin E supplementation enhances cell-mediated immunity in healthy elderly subjects, Am. J. Clin. Nutr., 52, 557, 1990.
108. Meydani, S.N., Meydani, M., Blumberg, J.B., Leka, L.S., Siber, G., Loszewski, R., Thompson, C., Pedrosa, M.C., Diamond, R.D., and Stollar, B.D., Vitamin E supplementation and in vivo immune response in healthy elderly subjects: a randomized controlled trial, JAMA, 277, 1380, 1997.
109. Han, S.N., Adolfsson, O., and Meydani, S.N., Vitamin E and enhancement of the immune response in the aged: cellular and molecular mechanisms, in The Antioxidant Vitamins C and E, Packer, L., Traber, M.G., Kramer, K., and Frei, B., Eds., AOCS Press, Champaign, IL, 2002, pp. 216.
110. Beharka, A.A., Wu, D., Serafini, M., and Meydani, S.N., Mechanism of vitamin E inhibition of cyclooxygenase activity in macrophages from old mice: role of peroxynitrite, Free Radic. Biol. Med., 32, 503, 2002.
111. Jiang, Q., Elson-Schwab, I., Courtemanche, C., and Ames, B.N., Gamma-tocopherol and its major metabolite, in contrast to alpha-tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells, Proc. Natl. Acad. Sci. USA, 97, 11494, 2000.
112. Ross, A.C., Vitamin A and retinoids, in Nutrition in Health and Disease, 9th ed., Shils, M., Olson, J.A., Shike, M., and Ross, A.C., Eds., Williams & Wilkins, Baltimore, 1999, p. 305.
113. Ponnamperuma, R.M., Shimizu, Y., Kirchhof, S.M., and De Luca, L.M., Beta-carotene fails to act as a tumor promoter, induces RAR expression, and prevents carcinoma formation in a two-stage model of skin carcinogenesis in male Sencar mice, Nutr. Cancer, 37, 82, 2000.
114. Chen, L.C., Sly, L., Jones, C.S., Tarone, R., and De Luca, L.M., Differential effects of dietary betacarotene on papilloma and carcinoma formation induced by an initiation-promotion protocol in SENCAR mouse skin, Carcinogenesis, 14, 713, 1993.
115. Mathews-Roth, M.M. and Krinsky, N.I., Carotenoids affect development of UV-B induced skin cancer, Photochem. Photobiol., 46, 507, 1987.
116. Black, H.S., Okotie-Eboh, G., and Gerguis, J., Diet potentiates the UV-carcinogenic response to betacarotene, Nutr. Cancer, 37, 173, 2000.
117. Krol, E.S., Kramer-Stickland, K.A., and Liebler, D.C., Photoprotective actions of topically applied vitamin E, Drug Metab. Rev., 32, 413, 2000.
118. Mitchel, R.E. and McCann, R., Vitamin E is a complete tumor promoter in mouse skin, Carcinogenesis, 14, 659, 1993.
119. Sawant, S.S. and Kandarkar, S.V., Role of vitamins C and E as chemopreventive agents in the hamster cheek pouch treated with the oral carcinogen-DMBA, Oral. Dis., 6, 241, 2000.
120. Schwartz, J.L., Sloane, D., and Shklar, G., Prevention and inhibition of oral cancer in the hamster buccal pouch model associated with carotenoid immune enhancement, Tumour Biol., 10, 297, 1989.
121. Shklar, G., Schwartz, J., Trickler, D., and Reid, S., Regression of experimental cancer by oral administration of combined alpha-tocopherol and beta-carotene, Nutr. Cancer, 12, 321, 1989.
122. Woutersen, R.A., Appel, M.J., and Van Garderen-Hoetmer, A., Modulation of pancreatic carcinogenesis by antioxidants, Food Chem. Toxicol., 37, 981, 1999.
123. Majima, T., Tsutsumi, M., Nishino, H., Tsunoda, T., and Konishi, Y., Inhibitory effects of betacarotene, palm carotene, and green tea polyphenols on pancreatic carcinogenesis initiated by Nnitorsobis (2-oxopropyl)amine in Syrian golden hamsters, Pancreas, 16, 13, 1998.
124. Appel, M.J. and Woutersen, R.A., Effects of dietary beta-carotene and selenium on initiation and promotion of pancreatic carcinogenesis in azaserine-treated rats, Carcinogenesis, 17, 1411, 1996.
125. Factor, V.M., Laskowska, D., Jensen, M.R., Woitach, J.T., Popescu, N.C., and Thorgeirsson, S.S., Vitamin E reduces chromosomal damage and inhibits hepatic tumor formation in a transgenic mouse model, Proc. Natl. Acad. Sci. USA, 97, 2196, 2000.
126. Kakizaki, S., Takagi, H., Fukusato, T., Toyoda, M., Horiguchi, N., Sato, K., Takayama, H., Nagamine, T., and Mori, M., Effect of alpha-tocopherol on hepatocarcinogenesis in transforming growth factoralpha (TGF-alpha) transgenic mice treated with diethylnitrosamine, Int. J. Vitam. Nutr. Res., 71, 261, 2001.
127. Ziegler, R.G., Mayne, S.T., and Swanson, C.A., Nutrition and lung cancer, Cancer Causes Control, 7, 157, 1996.
128. Stram, D.O., Huberman, M., and Wu, A.H., Is residual confounding a reasonable explanation for the apparent protective effects of beta-carotene found in epidemiologic studies of lung cancer in smokers?, Am. J. Epidemiol., 155, 622, 2002.
129. Knekt, P., Role of vitamin E in the prophylaxis of cancer, Ann. Med., 23, 3, 1991.
130. Block, G., Epidemiologic evidence regarding vitamin C and cancer, Am. J. Clin. Nutr., 54, 1310S, 1991.
131. Ziegler, R.G., Vegetables, fruits, and carotenoids and the risk of cancer, Am. J. Clin. Nutr., 53, 251S, 1991.
132. Enstrom, J.E., Kanim, L.E., and Klein, M.A., Vitamin C intake and mortality among a sample of the United States population, Epidemiology, 3, 194, 1992.
133. Shibata, A., Paganini-Hill, A., Ross, R.K., and Henderson, B.E., Intake of vegetables, fruits, betacarotene, vitamin C and vitamin supplements and cancer incidence among the elderly: a prospective study, Br. J. Cancer, 66, 673, 1992.
134. Pandey, D.K., Shekelle, R., Selwyn, B.J., Tangney, C., and Stamler, J., The Western Electric Study:dietary vitamin C and beta-carotene and risk of death in middle-aged men, Am. J. Epidemiol., 142, 1269, 1995.
135. Losonczy, K.G., Harris, T.B., and Havlik, R.J., Vitamin E and vitamin C supplement use and risk of all-cause and coronary heart disease mortality in older persons: the Established Populations for Epidemiologic Studies of the Elderly, Am. J. Clin. Nutr., 64, 190, 1996.
136. Sahyoun, N.R., Jacques, P.F., and Russell, R.M., Carotenoids, vitamins C and E, and mortality in an elderly population, Am. J. Epidemiol., 144, 501, 1996.
137. Eichholzer, M., Stahelin, H.B., Gey, K.F., Ludin, E., and Bernasconi, F., Prediction of male cancer mortality by plasma levels of interacting vitamins: 17-year follow-up of the prospective Basel study, Int. J. Cancer, 66, 145, 1996.
138. Loria, C.M., Klag, M.J., Caulfield, L.E., and Whelton, P.K., Vitamin C status and mortality in US adults, Am. J. Clin. Nutr., 72, 139, 2000.
139. Khaw, K.T., Bingham, S., Welch, A., Luben, R., Wareham, N., Oakes, S., and Day, N., European Prospective Investigation into Cancer and Nutrition: relation between plasma ascorbic acid and mortality in men and women in EPIC-Norfolk prospective study: a prospective population study, Lancet, 357, 657, 2001.
140. Kilander, L., Berglund, L., Boberg, M., Vessby, B., and Lithell, H., Education, lifestyle factors and mortality from cardiovascular disease and cancer: a 25-year follow-up of Swedish 50-year-old men, Int. J. Epidemiol., 30, 1119, 2001.
141. Martini, M.C., Campbell, D.R., Gross, M.D., Grandits, G.A., Potter, J.D., and Slavin, J.L., Plasma carotenoids as biomarkers of vegetable intake: the University of Minnesota Cancer Prevention Research Unit Feeding Studies, Cancer Epidemiol. Biomarkers Prev., 4, 491, 1995.
142. McEligot, A.J., Rock, C.L., Flatt, S.W., Newman, V., Faerber, S., and Pierce, J.P., Plasma carotenoids are biomarkers of long-term high vegetable intake in women with breast cancer, J. Nutr., 129, 2258, 1999.
143. Van Hoydonck, P.G., Temme, E.H., and Schouten, E.G., A dietary oxidative balance score of vitamin C, beta-carotene and iron intakes and mortality risk in male smoking Belgians, J. Nutr., 132, 756, 2002.
144. Knekt, P., Jarvinen, R., Seppanen, R., Rissanen, A., Aromaa, A., Heinonen, O.P., Albanes, D., Heinonen, M., Pukkala, E., and Teppo, L., Dietary antioxidants and the risk of lung cancer, Am. J. Epidemiol., 134, 471, 1991.
145. Chow, W.H., Schuman, L.M., McLaughlin, J.K., Bjelke, E., Gridley, G., Wacholder, S., Chien, H.T., and Blot, W.J., A cohort study of tobacco use, diet, occupation, and lung cancer mortality, Cancer Causes Control, 3, 247, 1992.
146. Steinmetz, K.A., Potter, J.D., and Folsom, A.R., Vegetables, fruit, and lung cancer in the Iowa Women’s Health Study, Cancer Res., 53, 536, 1993.
147. Comstock, G.W., Alberg, A.J., Huang, H.Y., Wu, K., Burke, A.E., Hoffman, S.C., Norkus, E.P., Gross, M., Cutler, R.G., Morris, J.S., Spate, V.L., and Helzlsouer, K.J., The risk of developing lung cancer associated with antioxidants in the blood: ascorbic acid, carotenoids, alpha-tocopherol, selenium, and total peroxyl radical absorbing capacity, Cancer Epidemiol. Biomarkers Prev., 6, 907, 1997.
148. Ocke, M.C., Bueno-de-Mesquita, H.B., Feskens, E.J., van Staveren, W.A., and Kromhout, D., The Zutphen study: repeated measurements of vegetables, fruits, beta-carotene, and vitamins C and E in relation to lung cancer, Am. J. Epidemiol., 145, 358, 1997.
149. Yong, L.C., Brown, C.C., Schatzkin, A., Dresser, C.M., Slesinski, M.J., Cox, C.S., and Taylor, P.R., First National Health and Nutrition Examination Survey, NHANES I epidemiologic followup study:intake of vitamins E, C, and A and risk of lung cancer, Am. J. Epidemiol., 146, 231, 1997.
150. Bandera, E.V., Freudenheim, J.L., Marshall, J.R., Zielezny, M., Priore, R.L., Brasure, J., Baptiste, M., and Graham, S., Diet and alcohol consumption and lung cancer risk in the New York State Cohort (United States), Cancer Causes Control, 8, 828, 1997.
151. Voorrips, L.E., Goldbohm, R.A., Brants, H.A., van Poppel, G.A., Sturmans, F., Hermus, R.J., and van den Brandt, P.A., A prospective cohort study on antioxidant and folate intake and male lung cancer risk, Cancer Epidemiol. Biomarkers Prev., 9, 357, 2000.
152. Woodson, K., Tangrea, J.A., Barrett, M.J., Virtamo, J., Taylor, P.R., and Albanes, D., Serum alphatocopherol and subsequent risk of lung cancer among male smokers, J. Natl. Cancer Inst., 91, 1738, 1999.
153. Michaud, D.S., Feskanich, D., Rimm, E.B., Colditz, G.A., Speizer, F.E., Willett, W.C., and Giovannucci, E., Intake of specific carotenoids and risk of lung cancer in two prospective US cohorts, Am. J. Clin. Nutr., 72, 990, 2000.
154. Holick, C.N., Michaud, D.S., Stolzenberg-Solomon, R., Mayne, S.T., Pietinen, P., Taylor, P.R., Virtamo, J., and Albanes, D., Dietary carotenoids, serum beta-carotene, and retinol and risk of lung cancer in the alpha-tocopherol, beta-carotene cohort study, Am. J. Epidemiol., 156, 536, 2002.
155. Rohan, T.E., Jain, M., Howe, G.R., and Miller, A.B., A cohort study of dietary carotenoids and lung cancer risk in women (Canada), Cancer Causes Control, 13, 231, 2002.
156. Kritchevsky, S.B., Bush, A.J., Pahor, M., and Gross, M.D., Serum carotenoids and markers of inflammation in nonsmokers, Am. J. Epidemiol., 152, 1065, 2000.
157. Erlinger, T.P., Guallar, E., Miller, III, E.R., Stolzenberg-Solomon, R., and Appel, L.J., Relationship between systemic markers of inflammation and serum beta-carotene levels, Arch. Intern. Med., 161, 1903, 2001.
158. Ekstrom, A.M., Serafini, M., Nyren, O., Hansson, L.E., Ye, W., and Wolk, A., Dietary antioxidant intake and the risk of cardia cancer and noncardia cancer of the intestinal and diffuse types: a population-based case-control study in Sweden, Int. J. Cancer, 87, 133, 2000.
159. Kaaks, R., Tuyns, A.J., Haelterman, M., and Riboli, E., Nutrient intake patterns and gastric cancer risk: a case-control study in Belgium, Int. J. Cancer, 78, 415, 1998.
160. Mayne, S.T., Risch, H.A., Dubrow, R., Chow, W.H., Gammon, M.D., Vaughan, T.L., Farrow, D.C., Schoenberg, J.B., Stanford, J.L., Ahsan, H., West, A.B., Rotterdam, H., Blot, W.J., and Fraumeni, Jr., J.F., Nutrient intake and risk of subtypes of esophageal and gastric cancer, Cancer Epidemiol. Biomarkers Prev., 10, 1055, 2001.
161. Palli, D., Russo, A., and Decarli, A., Dietary patterns, nutrient intake and gastric cancer in a highrisk area of Italy, Cancer Causes Control, 12, 163, 2001.
162. Botterweck, A.A., van den Brandt, P.A., and Goldbohm, R.A., Vitamins, carotenoids, dietary fiber, and the risk of gastric carcinoma: results from a prospective study after 6.3 years of follow-up, Cancer, 88, 737, 2000.
163. Chyou, P.H., Nomura, A.M., Hankin, J.H., and Stemmermann, G.N., A case-cohort study of diet and stomach cancer, Cancer Res., 50, 7501, 1990.
164. Zheng, W., Sellers, T.A., Doyle, T.J., Kushi, L.H., Potter, J.D., and Folsom, A.R., Retinol, antioxidant vitamins, and cancers of the upper digestive tract in a prospective cohort study of postmenopausal women, Am. J. Epidemiol., 142, 955, 1995.
165. Stahelin, H.B., Gey, K.F., Eichholzer, M., Ludin, E., Bernasconi, F., Thurneysen, J., and Brubacher, G., Plasma antioxidant vitamins and subsequent cancer mortality in the 12-year follow-up of the prospective Basel Study, Am. J. Epidemiol., 133, 766, 1991.
166. Jacobs, E.J., Connell, C.J., McCullough, M.L., Chao, A., Jonas, C.R., Rodriguez, C., Calle, E.E., and Thun, M.J., Vitamin C, vitamin E, and multivitamin supplement use and stomach cancer mortality in the Cancer Prevention Study II cohort, Cancer Epidemiol. Biomarkers Prev., 11, 35, 2002.
167. Reed, P.I., Vitamin C, Helicobacter pylori infection and gastric carcinogenesis, Int. J. Vitam. Nutr. Res., 69, 220, 1999.
168. De Stefani, E., Boffetta, P., Brennan, P., Deneo-Pellegrini, H., Carzoglio, J.C., Ronco, A., and Mendilaharsu, M., Dietary carotenoids and risk of gastric cancer: a case-control study in Uruguay, Eur. J. Cancer Prev., 9, 329, 2000.
169. Bostick, R.M., Diet and colon cancer, in Preventive Nutrition: the Comprehensive Guide for Health Professionals, 2nd ed., Bendich, A. and Deckelbaum, R.J., Eds., Humana Press, Totowa, NJ, 2001, p. 47.
170. Bostick, R.M., Potter, J.D., McKenzie, D.R., Sellers, T.A., Kushi, L.H., Steinmetz, K.A., and Folsom, A.R., Reduced risk of colon cancer with high intake of vitamin E: the Iowa Women’s Health Study, Cancer Res., 53, 4230, 1993.
171. Jacobs, E.J., Connell, C.J., Patel, A.V., Chao, A., Rodriguez, C., Seymour, J., McCullough, M.L., Calle, E.E., and Thun, M.J., Vitamin C and vitamin E supplement use and colorectal cancer mortality in a large American Cancer Society cohort, Cancer Epidemiol. Biomarkers Prev., 10, 17, 2001.
172. Malila, N., Virtamo, J., Virtanen, M., Pietinen, P., Albanes, D., and Teppo, L., Dietary and serum alpha-tocopherol, beta-carotene and retinol, and risk for colorectal cancer in male smokers, Eur. J. Clin. Nutr., 56, 615, 2002.
173. Longnecker, M.P., Martin-Moreno, J.M., Knekt, P., Nomura, A.M., Schober, S.E., Stahelin, H.B., Wald, N.J., Gey, K.F., and Willett, W.C., Serum alpha-tocopherol concentration in relation to subsequent colorectal cancer: pooled data from five cohorts, J. Natl. Cancer Inst., 84, 430, 1992.
174. Wu, K., Willett, W.C., Chan, J.M., Fuchs, C.S., Colditz, G.A., Rimm, E.B., and Giovannucci, E.L., A prospective study on supplemental vitamin E intake and risk of colon cancer in women and men, Cancer Epidemiol. Biomarkers Prev., 11, 1298, 2002.
175. Sellers, T.A., Bazyk, A.E., Bostick, R.M., Kushi, L.H., Olson, J.E., Anderson, K.E., Lazovich, D., and Folsom, A.R., Diet and risk of colon cancer in a large prospective study of older women: an analysis stratified on family history (Iowa, United States), Cancer Causes Control, 9, 357, 1998.
176. Michaud, D.S., Spiegelman, D., Clinton, S.K., Rimm, E.B., Willett, W.C., and Giovannucci, E., Prospective study of dietary supplements, macronutrients, micronutrients, and risk of bladder cancer in US men, Am. J. Epidemiol., 152, 1145, 2000.
177. Zeegers, M.P., Goldbohm, R.A., and Brandt, P.A., Are retinol, vitamin C, vitamin E, folate and carotenoids intake associated with bladder cancer risk? Results from the Netherlands Cohort Study, Br. J. Cancer, 85, 977, 2001.
178. Michaud, D.S., Pietinen, P., Taylor, P.R., Virtanen, M., Virtamo, J., and Albanes, D., Intakes of fruits and vegetables, carotenoids and vitamins A, E, C in relation to the risk of bladder cancer in the ATBC cohort study, Br. J. Cancer, 87, 960, 2002.
179. Jacobs, E.J., Henion, A.K., Briggs, P.J., Connell, C.J., McCullough, M.L., Jonas, C.R., Rodriguez, C., Calle, E.E., and Thun, M.J., Vitamin C and vitamin E supplement use and bladder cancer mortality in a large cohort of US men and women, Am. J. Epidemiol., 156, 1002, 2002.
180. Knekt, P., Aromaa, A., Maatela, J., Alfthan, G., Aaran, R.K., Nikkari, T., Hakama, M., Hakulinen, T., and Teppo, L., Serum micronutrients and risk of cancers of low incidence in Finland, Am. J. Epidemiol., 134, 356, 1991.
181. Daviglus, M.L., Dyer, A.R., Persky, V., Chavez, N., Drum, M., Goldberg, J., Liu, K., Morris, D.K., Shekelle, R.B., and Stamler, J., Dietary beta-carotene, vitamin C, and risk of prostate cancer: results from the Western Electric Study, Epidemiology, 7, 472, 1996.
182. Schuurman, A.G., Goldbohm, R.A., Brants, H.A., and van den Brandt, P.A., A prospective cohort study on intake of retinol, vitamins C and E, and carotenoids and prostate cancer risk (Netherlands), Cancer Causes Control, 13, 573, 2002.
183. Hsing, A.W., Comstock, G.W., Abbey, H., and Polk, B.F., Serologic precursors of cancer: retinol, carotenoids, and tocopherol and risk of prostate cancer, J. Natl. Cancer Inst., 82, 941, 1990.
184. Nomura, A.M., Stemmermann, G.N., Lee, J., and Craft, N.E., Serum micronutrients and prostate cancer in Japanese Americans in Hawaii, Cancer Epidemiol. Biomarkers Prev., 6, 487, 1997.
185. Gann, P.H., Ma, J., Giovannucci, E., Willett, W., Sacks, F.M., Hennekens, C.H., and Stampfer, M.J., Lower prostate cancer risk in men with elevated plasma lycopene levels: results of a prospective analysis, Cancer Res., 59, 1225, 1999.
186. Chan, J.M., Stampfer, M.J., Ma, J., Rimm, E.B., Willett, W.C., and Giovannucci, E.L., Supplemental vitamin E intake and prostate cancer risk in a large cohort of men in the United States, Cancer Epidemiol. Biomarkers Prev., 8, 893, 1999.
187. Helzlsouer, K.J., Huang, H.Y., Alberg, A.J., Hoffman, S., Burke, A., Norkus, E.P., Morris, J.S., and Comstock, G.W., Association between alpha-tocopherol, gamma-tocopherol, selenium, and subsequent prostate cancer, J. Natl. Cancer Inst., 92, 2018, 2000.
188. Giovannucci, E., Ascherio, A., Rimm, E.B., Stampfer, M.J., Colditz, G.A., and Willett, W.C., Intake of carotenoids and retinol in relation to risk of prostate cancer, J. Natl. Cancer Inst., 87, 1767, 1995.
189. Ambrosone, C.B., Oxidants and antioxidants in breast cancer, Antioxid. Redox Signal., 2, 903, 2000.
190. Graham, S., Zielezny, M., Marshall, J., Priore, R., Freudenheim, J., Brasure, J., Haughey, B., Nasca, P., and Zdeb, M., Diet in the epidemiology of postmenopausal breast cancer in the New York State Cohort, Am. J. Epidemiol., 136, 1327, 1992.
191. Rohan, T.E., Howe, G.R., Friedenreich, C.M., Jain, M., and Miller, A.B., Dietary fiber, vitamins A, C, and E, and risk of breast cancer: a cohort study, Cancer Causes Control, 4, 29, 1993.
192. Kushi, L.H., Fee, R.M., Sellers, T.A., Zheng, W., and Folsom, A.R., Iowa Women’s Health Study:intake of vitamins A, C, and E and postmenopausal breast cancer, Am. J. Epidemiol., 144, 165, 1996.
193. Verhoeven, D.T., Assen, N., Goldbohm, R.A., Dorant, E., van’t Veer, P., Sturmans, F., Hermus, R.J., and van den Brandt, P.A., Vitamins C and E, retinol, beta-carotene and dietary fibre in relation to breast cancer risk: a prospective cohort study, Br. J. Cancer, 75, 149, 1997.
194. Zhang, S., Hunter, D.J., Forman, M.R., Rosner, B.A., Speizer, F.E., Colditz, G.A., Manson, J.E., Hankinson, S.E., and Willett, W.C., Dietary carotenoids and vitamins A, C, and E and risk of breast cancer, J. Natl. Cancer Inst., 91, 547, 1999.
195. Michels, K.B., Holmberg, L., Bergkvist, L., Ljung, H., Bruce, A., and Wolk, A., Dietary antioxidant vitamins, retinol, and breast cancer incidence in a cohort of Swedish women, Int. J. Cancer, 91, 563, 2001.
196. Wu, K., Helzlsouer, K.J., Alberg, A.J., Comstock, G.W., Norkus, E.P., and Hoffman, S.C., A prospective study of plasma ascorbic acid concentrations and breast cancer (United States), Cancer Causes Control, 11, 279, 2000.
197. Dorgan, J.F., Sowell, A., Swanson, C.A., Potischman, N., Miller, R., Schussler, N., and Stephenson, Jr., H.E., Relationships of serum carotenoids, retinol, alpha-tocopherol, and selenium with breast cancer risk: results from a prospective study in Columbia, Missouri (United States), Cancer Causes Control, 9, 89, 1998.
198. Hulten, K., Van Kappel, A.L., Winkvist, A., Kaaks, R., Hallmans, G., Lenner, P., and Riboli, E., Carotenoids, alpha-tocopherols, and retinol in plasma and breast cancer risk in northern Sweden, Cancer Causes Control, 12, 529, 2001.
199. Sato, R., Helzlsouer, K.J., Alberg, A.J., Hoffman, S.C., Norkus, E.P., and Comstock, G.W., Prospective study of carotenoids, tocopherols, and retinoid concentrations and the risk of breast cancer, Cancer Epidemiol. Biomarkers Prev., 11, 451, 2002.
200. Jumaan, A.O., Holmberg, L., Zack, M., Mokdad, A.H., Ohlander, E.M., Wolk, A., and Byers, T., Betacarotene intake and risk of postmenopausal breast cancer, Epidemiology, 10, 49, 1999.
201. Toniolo, P., Van Kappel, A.L., Akhmedkhanov, A., Ferrari, P., Kato, I., Shore, R.E., and Riboli, E., Serum carotenoids and breast cancer, Am. J. Epidemiol., 153, 1142, 2001.
202. Taylor, P.R., Li, B., Dawsey, S.M., Li, J.Y., Yang, C.S., Guo, W., and Blot, W.J., Linxian Nutrition Intervention Trials Study Group: Prevention of esophageal cancer: the nutrition intervention trials in Linxian, China, Cancer Res. 54, 2029s, 1994.
203. Gail, M.H., You, W.C., Chang, Y.S., Zhang, L., Blot, W.J., Brown, L.M., Groves, F.D., Heinrich, J.P., Hu, J., Jin, M.L., Li, J.Y., Liu, W.D., Ma, J.L., Mark, S.D., Rabkin, C.S., Fraumeni, Jr., J.F., and Xu, G.W., Factorial trial of three interventions to reduce the progression of precancerous gastric lesions in Shandong, China: design issues and initial data, Control. Clin. Trials, 19, 352, 1998.
204. Hennekens, C.H., Buring, J.E., Manson, J.E., Stampfer, M., Rosner, B., Cook, N.R., Belanger, C., LaMotte, F., Gaziano, J.M., Ridker, P.M., Willett, W., and Peto, R., Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease, New England J. Med., 334, 1145, 1996.
205. Cook, N.R., Lee, I.M., Manson, J.E., Buring, J.E., and Hennekens, C.H., Effects of beta-carotene supplementation on cancer incidence by baseline characteristics in the Physicians’ Health Study (United States), Cancer Causes Control, 11, 617, 2000.
206. Lee, I.M., Cook, N.R., Manson, J.E., Buring, J.E., and Hennekens, C.H., Beta-carotene supplementation and incidence of cancer and cardiovascular disease: the Women’s Health Study, J. Natl. Cancer Inst., 91, 2102, 1999.
207. Yeum, K.J. and Russell, R.M., Carotenoid bioavailability and bioconversion, Annu. Rev. Nutr., 22, 483, 2002.
208. Wang, X.D. and Russell, R.M., Procarcinogenic and anticarcinogenic effects of beta-carotene, Nutr. Rev., 57, 263, 1999.
209. Wang, X.D., Liu, C., Bronson, R.T., Smith, D.E., Krinsky, N.I., and Russell, M., Retinoid signaling and activator protein-1 expression in ferrets given beta-carotene supplements and exposed to tobacco smoke, J. Natl. Cancer Inst., 91, 60, 1999.
210. Gradelet, S., Leclerc, J., Siess, M.H., and Astorg, P.O., Beta-Apo-8'-carotenal, but not beta-carotene, is a strong inducer of liver cytochromes P4501A1 and 1A2 in rat, Xenobiotica, 26, 909, 1996.
211. Paolini, M., Antelli, A., Pozzetti, L., Spetlova, D., Perocco, P., Valgimigli, L., Pedulli, G.F., and Cantelli-Forti, G., Induction of cytochrome P450 enzymes and over-generation of oxygen radicals in beta-carotene supplemented rats, Carcinogenesis, 22, 1483, 2001.
212. Salgo, M.G., Cueto, R., Winston, G.W., and Pryor, W.A., Beta carotene and its oxidation products have different effects on microsome mediated binding of benzo[a]pyrene to DNA, Free Radic. Biol. Med., 26, 162, 1999.
213. Omenn, G.S., Goodman, G.E., Thornquist, M.D., Balmes, J., Cullen, M.R., Glass, A., Keogh, J.P., Meyskens, Jr., F.L., Valanis, B., Williams, Jr., J.H., Barnhart, S., Cherniack, M.G., Brodkin, C.A., and Hammar, S., Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial, J. Natl. Cancer Inst., 88, 1550, 1996.
214. Albanes, D., Heinonen, O.P., Taylor, P.R., Virtamo, J., Edwards, B.K., Rautalahti, M., Hartman, A.M., Palmgren, J., Freedman, L.S., Haapakoski, J., Barrett, M.J., Pietinen, P., Malila, N., Tala, E., Liippo, K., Salomaa, E.R., Tangrea, J.A., Teppo, L., Askin, F.B., Taskinen, E., Erozan, Y., Greenwald, P., and Huttunen, J.K., Alpha-tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance, J. Natl. Cancer Inst., 88, 1560, 1996.
215. Liu, C., Wang, X.D., Bronson, R.T., Smith, D.E., Krinsky, N.I., and Russell, R.M., Effects of physiological versus pharmacological beta-carotene supplementation on cell proliferation and histopathological changes in the lungs of cigarette smoke-exposed ferrets, Carcinogenesis, 21, 2245, 2000.
216. Lykkesfeldt, J., Christen, S., Wallock, L.M., Chang, H.H., Jacob, R.A., and Ames, B.N., Ascorbate is depleted by smoking and repleted by moderate supplementation: a study in male smokers and nonsmokers with matched dietary antioxidant intakes, Am. J. Clin. Nutr., 71, 530, 2000.
217. Tribble, D.L., Giuliano, L.J., and Fortmann, S.P., Reduced plasma ascorbic acid concentrations in nonsmokers regularly exposed to environmental tobacco smoke, Am. J. Clin. Nutr., 58, 886, 1993.
218. Burke, M., Edge, R., Land, E.J., and Truscott, T.G., Characterisation of carotenoid radical cations in liposomal environments: interaction with vitamin C, J. Photochem. Photobiol. B, 60, 1, 2001.
219. Yeum, K.J., dos Anjos Ferreira, A.L., Smith, D., Krinsky, N.I., and Russell, R.M., The effect of alpha-tocopherol on the oxidative cleavage of beta-carotene, Free Radical Biol. Med., 29, 105, 2000.
220. Cook, N.R., Stampfer, M.J., Ma, J., Manson, J.E., Sacks, F.M., Buring, J.E., and Hennekens, C.H., Beta-carotene supplementation for patients with low baseline levels and decreased risks of total and prostate carcinoma, Cancer, 86, 1783, 1999.
221. Shklar, G. and Schwartz, J.L., Vitamin E inhibits experimental carcinogenesis and tumour angiogenesis, Eur. J. Cancer B Oral Oncol., 32B, 114, 1996.
222. Woodson, K., Triantos, S., Hartman, T., Taylor, P.R., Virtamo, J., and Albanes, D., Long-term alphatocopherol supplementation is associated with lower serum vascular endothelial growth factor levels, Anticancer Res., 22, 375, 2002.
223. Greenberg, E.R., Baron, J.A., Stukel, T.A., Stevens, M.M., Mandel, J.S., Spencer, S.K., Elias, P.M., Lowe, N., Nierenberg, D.W., Bayrd, G. et al., The Skin Cancer Prevention Study Group: a clinical trial of beta carotene to prevent basal-cell and squamous-cell cancers of the skin, New England J. Med., 323, 789, 1990.
224. Frieling, U.M., Schaumberg, D.A., Kupper, T.S., Muntwyler, J., and Hennekens, C.H., A randomized, 12-year primary-prevention trial of beta carotene supplementation for nonmelanoma skin cancer in the physician’s health study, Arch. Dermatol., 136, 179, 2000.
225. Mayne, S.T., Cartmel, B., Baum, M., Shor-Posner, G., Fallon, B.G., Briskin, K., Bean, J., Zheng, T., Cooper, D., Friedman, C., and Goodwin, Jr., W.J., Randomized trial of supplemental beta-carotene to prevent second head and neck cancer, Cancer Res., 61, 1457, 2001.
226. Albanes, D., Malila, N., Taylor, P.R., Huttunen, J.K., Virtamo, J., Edwards, B.K., Rautalahti, M., Hartman, A.M., Barrett, M.J., Pietinen, P., Hartman, T.J., Sipponen, P., Lewin, K., Teerenhovi, L., Hietanen, P., Tangrea, J.A., Virtanen, M., and Heinonen, O.P., Effects of supplemental alpha-tocopherol and beta-carotene on colorectal cancer: results from a controlled trial (Finland), Cancer Causes Control, 11, 197, 2000.
227. Virtamo, J., Edwards, B.K., Virtanen, M., Taylor, P.R., Malila, N., Albanes, D., Huttunen, J.K., Hartman, A.M., Hietanen, P., Maenpaa, H., Koss, L., Nordling, S., and Heinonen, O.P., Effects of supplemental alpha-tocopherol and beta-carotene on urinary tract cancer: incidence and mortality in a controlled trial (Finland), Cancer Causes Control, 11, 933, 2000.
228. Malila, N., Taylor, P.R., Virtanen, M.J., Korhonen, P., Huttunen, J.K., Albanes, D., and Virtamo, J., Effects of alpha-tocopherol and beta-carotene supplementation on gastric cancer incidence in male smokers (ATBC Study, Finland), Cancer Causes Control, 13, 617, 2002.
229. Rautalahti, M.T., Virtamo, J.R., Taylor, P.R., Heinonen, O.P., Albanes, D., Haukka, J.K., Edwards, B.K., Karkkainen, P.A., Stolzenberg-Solomon, R.Z., and Huttunen, J., The effects of supplementation with alpha-tocopherol and beta-carotene on the incidence and mortality of carcinoma of the pancreas in a randomized, controlled trial, Cancer, 86, 37, 1999.
230. Lodi, G., Sardella, A., Bez, C., Demarosi, F., and Carrassi, A., Systematic review of randomized trials for the treatment of oral leukoplakia, J. Dent. Educ., 66, 896, 2002.
231. Garewal, H.S., Meyskens, Jr., F.L., Killen, D., Reeves, D., Kiersch, T.A., Elletson, H., Strosberg, A., King, D., and Steinbronn, K., Response of oral leukoplakia to beta-carotene, J. Clin. Oncol., 8, 1715, 1990.
232. Toma, S., Benso, S., Albanese, E., Palumbo, R., Cantoni, E., Nicolo, G., and Mangiante, P., Treatment of oral leukoplakia with beta-carotene, Oncology, 49, 77, 1992.
233. Kaugars, G.E., Silverman, Jr., S., Lovas, J.G., Brandt, R.B., Riley, W.T., Dao, Q., Singh, V.N., and Gallo, J., A clinical trial of antioxidant supplements in the treatment of oral leukoplakia, Oral Surg. Oral Med. Oral Pathol., 78, 462, 1994.
234. Barth, T.J., Zoller, J., Kubler, A., Born, I.A., and Osswald, H., Redifferentiation of oral dysplastic mucosa by the application of the antioxidants beta-carotene, alpha-tocopherol and vitamin C, Int. J. Vitam. Nutr. Res., 67, 368, 1997.
235. Garewal, H.S., Katz, R.V., Meyskens, F., Pitcock, J., Morse, D., Friedman, S., Peng, Y., Pendrys, D.G., Mayne, S., Alberts, D., Kiersch, T., and Graver, E., Beta-carotene produces sustained remissions in patients with oral leukoplakia: results of a multicenter prospective trial, Arch. Otolaryngol. Head Neck Surg., 125, 1305, 1999.
236. Zaride, D., Evstifeeva, T., and Boyle, P., Chemoprevention of oral leukoplakia and chromic esophagitis in an area of high incidence of oral and esophagent cancer, Ann. Epidemiol. 3, 225, 1993
237. Sankaranarayanan, R., Mathew, B., Varghese, C., Sudhakaran, P.R., Menon, V., Jayadeep, A., Nair, M.K., Mathews, C., Mahalingam, T.R., Balaram, P., and Nair, P.P., Chemoprevention of oral leukoplakia with vitamin A and beta carotene: an assessment, Oral Oncol., 33, 231, 1997.
238. Giuliano, A.R. and Gapstur, S., Can cervical dysplasia and cancer be prevented with nutrients?, Nutr. Rev., 56, 9, 1998.
239. Einstein, M.H. and Goldberg, G.L., Human papilloma virus and cervical neoplasia, Cancer Invest., 20, 1080, 2002.
240. de Vet, H.C., Knipschild, P.G., Willebrand, D., Schouten, H.J., and Sturmans, F., The effect of betacarotene on the regression and progression of cervical dysplasia: a clinical experiment, J. Clin. Epidemiol., 44, 273, 1991.
241. Romney, S.L., Ho, G.Y., Palan, P.R., Basu, J., Kadish, A.S., Klein, S., Mikhail, M., Hagan, R.J., Chang, C.J., and Burk, R.D., Effects of beta-carotene and other factors on outcome of cervical dysplasia and human papilloma virus infection, Gynecol. Oncol., 65, 483, 1997.
242. Keefe, K.A., Schell, M.J., Brewer, C., McHale, M., Brewster, W., Chapman, J.A., Rose, G.S., McMeeken, D.S., Lagerberg, W., Peng, Y.M., Wilczynski, S.P., Anton-Culver, H., Meyskens, F.L., and Berman, M.L., A randomized, double blind, Phase III trial using oral beta-carotene supplementation for women with high-grade cervical intraepithelial neoplasia, Cancer Epidemiol. Biomarkers Prev., 10, 1029, 2001.
243. Mackerras, D., Irwig, L., Simpson, J.M., Weisberg, E., Cardona, M., Webster, F., Walton, L., and Ghersi, D., Randomized double-blind trial of beta-carotene and vitamin C in women with minor cervical abnormalities, Br. J. Cancer, 79, 1448, 1999.
244. DeCosse, J.J., Adams, M.B., Kuzma, J.F., LoGerfo, P., and Condon, R.E., Effect of ascorbic acid on rectal polyps of patients with familial polyposis, Surgery, 78, 608, 1975.
245. Bussey, H.J., DeCosse, J.J., Deschner, E.E., Eyers, A.A., Lesser, M.L., Morson, B.C., Ritchie, S.M., Thomson, J.P., and Wadsworth, J., A randomized trial of ascorbic acid in polyposis coli, Cancer, 50, 1434, 1982.
246. Roncucci, L., Di Donato, P., Carati, L., Ferrari, A., Perini, M., Bertoni, G., Bedogni, G., Paris, B., Svanoni, F., Girola, M. et al., Colorectal Cancer Study Group of the University of Modena and the Health Care District 16: Antioxidant vitamins or lactulose for the prevention of the recurrence of colorectal adenomas, Dis. Colon Rectum, 36, 227, 1993.
247. Greenberg, E.R., Baron, J.A., Tosteson, T.D., Freeman, Jr., D.H., Beck, G.J., Bond, J.H., Colacchio, T.A., Coller, J.A., Frankl, H.D., Haile, R.W. et al., Polyp Prevention Study Group: a clinical trial of antioxidant vitamins to prevent colorectal adenoma, New England J. Med., 331, 141, 1994.
248. MacLennan, R., Macrae, F., Bain, C., Battistutta, D., Chapuis, P., Gratten, H., Lambert, J., Newland, R.C., Ngu, M., Russell, A. et al., The Australian Polyp Prevention Project: randomized trial of intake of fat, fiber, and beta carotene to prevent colorectal adenomas, J. Natl. Cancer Inst., 87, 1760, 1995.
249. McKeown-Eyssen, G., Holloway, C., Jazmaji, V., Bright-See, E., Dion, P., and Bruce, W.R., A randomized trial of vitamins C and E in the prevention of recurrence of colorectal polyps, Cancer Res., 48, 4701, 1988.
250. DeCosse, J.J., Miller, H.H., and Lesser, M.L., Effect of wheat fiber and vitamins C and E on rectal polyps in patients with familial adenomatous polyposis, J. Natl. Cancer Inst., 81, 1290, 1989.
251. Malila, N., Virtamo, J., Virtanen, M., Albanes, D., Tangrea, J.A., and Huttunen, J.K., The effect of alpha-tocopherol and beta-carotene supplementation on colorectal adenomas in middle-aged male smokers, Cancer Epidemiol. Biomarkers Prev., 8, 489, 1999.
252. Paganelli, G.M., Biasco, G., Brandi, G., Santucci, R., Gizzi, G., Villani, V., Cianci, M., Miglioli, M., and Barbara, L., Effect of vitamin A, C, and E supplementation on rectal cell proliferation in patients with colorectal adenomas, J. Natl. Cancer Inst., 84, 47, 1992.
253. Frommel, T.O., Mobarhan, S., Doria, M., Halline, A.G., Luk, G.D., Bowen, P.E., Candel, A., and Liao, Y., Effect of beta-carotene supplementation on indices of colonic cell proliferation, J. Natl. Cancer Inst., 87, 1781, 1995.
254. Cascinu, S., Ligi, M., Del Ferro, E., Foglietti, G., Cioccolini, P., Staccioli, M.P., Carnevali, A., Luigi Rocchi, M.B., Alessandroni, P., Giordani, P., Catalano, V., Polizzi, V., Agostinelli, R., Muretto, P., and Catalano, G., Effects of calcium and vitamin supplementation on colon cell proliferation in colorectal cancer, Cancer Invest., 18, 411, 2000.
255. Schorah, C.J., Vitamin C and gastric cancer prevention, in Vitamin C: the State of the Art in Disease Prevention Sixty Years after the Nobel Prize, Paoletti, R., Sies, H., Bug, J., Grossi, E., and Poli, A., Eds., Springer-Verlag, Milan, 1998, pp. 41.
256. Zhang, L., Blot, W.J., You, W.C., Chang, Y.S., Liu, X.Q., Kneller, R.W., Zhao, L., Liu, W.D., Li, J.Y., Jin, M.L. et al., Serum micronutrients in relation to pre-cancerous gastric lesions, Int. J. Cancer, 56, 650, 1994.
257. You, W.C., Zhang, L., Gail, M.H., Chang, Y.S., Liu, W.D., Ma, J.L., Li, J.Y., Jin, M.L., Hu, Y.R., Yang, C.S., Blaser, M.J., Correa, P., Blot, W.J., Fraumeni, Jr., J.F., and Xu, G.W., Gastric dysplasia and gastric cancer: Helicobacter pylori, serum vitamin C, and other risk factors, J. Natl. Cancer Inst., 92, 1607, 2000.
258. Zhang, Z.W., Patchett, S.E., Perrett, D., Domizio, P., and Farthing, M.J., Gastric alpha-tocopherol and beta-carotene concentrations in association with Helicobacter pylori infection, Eur. J. Gastroenterol. Hepatol., 12, 497, 2000.
259. Varis, K., Taylor, P.R., Sipponen, P., Samloff, I.M., Heinonen, O.P., Albanes, D., Harkonen, M., Huttunen, J.K., Laxen, F., and Virtamo, J., Helsinki Gastritis Study Group: gastric cancer and premalignant lesions in atrophic gastritis: a controlled trial on the effect of supplementation with alphatocopherol and beta-carotene, Scand. J. Gastroenterol., 33, 294, 1998.
260. Correa, P., Fontham, E.T., Bravo, J.C., Bravo, L.E., Ruiz, B., Zarama, G., Realpe, J.L., Malcom, G.T., Li, D., Johnson, W.D., and Mera, R., Chemoprevention of gastric dysplasia: randomized trial of antioxidant supplements and anti-Helicobacter pylori therapy, J. Natl. Cancer Inst., 92, 1881, 2000.
261. Zullo, A., Rinaldi, V., Hassan, C., Diana, F., Winn, S., Castagna, G., and Attili, A.F., Ascorbic acid and intestinal metaplasia in the stomach: a prospective, randomized study, Aliment. Pharmacol. Ther., 14, 1303, 2000.
262. Smith-Werner, S.A. and Giovannucci, E., Fruit and vegetable intake and cancer, in Nutritional Oncology, Heber, D., Blackburn, G.L., and Go, V.L., Eds., Academic Press, San Diego, 1999, pp. 153.
263. Anon., MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial, Lancet, 360, 23, 2002.
264. Woodson, K., Stewart, C., Barrett, M., Bhat, N.K., Virtamo, J., Taylor, P.R., and Albanes, D., Effect of vitamin intervention on the relationship between GSTM1, smoking, and lung cancer risk among male smokers, Cancer Epidemiol. Biomarkers Prev., 8, 965, 1999.