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Antioxidants and Cancer: Molecular Mechanisms

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 366))

Abstract

Because chemotherapy is often ineffective for the treatment of cancer, considerable efforts are being made to develop agents for “chemoprevention” that would prevent cancers from developing in the first place. Furthermore understanding the antitumorigenic mechanisms should further our comprehension of carcinogenesis mechanisms. In the following, possible molecular mechanisms by which antioxidants inhibit carcinogenesis are reviewed.

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References

  1. Jaffe, W. The influence of wheat germ oil on the production of tumors in rats by methylcholanthrene. Proc. Soc. Exp. Biol. Med. 111, 714–715 (1946).

    Google Scholar 

  2. Haber, S.L. and Wissler, R.W. Effect of vitamin E on carcinogenicity of methylcholanthrene. Proc. Soc. Exp. Biol. Med. 111, 774–775 (1962).

    CAS  Google Scholar 

  3. Graham, S. Results of case-control studies of diet and cancer in Buffalo, N. Y., Cancer Res. 43, 2409s–2413s (1983).

    CAS  Google Scholar 

  4. Shamberger, R.J. Relationship of selenium to cancer I inhibitory effect of selenium on carcinogenesis. J. Natl. Cancer Inst. 44, 931–936 (1970).

    PubMed  CAS  Google Scholar 

  5. Shamberger, R.J. Increase of peroxidation in carcinogenesis. J. Natl. Cancer Inst. 48, 1491–1497 (1972).

    PubMed  CAS  Google Scholar 

  6. Wattenberg, L.W. Inhibition of carcinogenic and toxic effect of polycyclic hydrocarbons by phenolic antioxidants and ethoxyquin. J. Natl. Cancer Inst. 48, 1425–1430 (1972).

    PubMed  CAS  Google Scholar 

  7. Hocman, G. Prevention of Cancer: Vegetables and Plants. Comp. Biochem. Physiol. 93B, 201–212 (1989).

    CAS  Google Scholar 

  8. Block, G., Patterson, B. and Subar, A. Fruit, vegetables, and cancer prevention: a review of the epidemiological evidence. Cancer 18, 1–29 (1992).

    CAS  Google Scholar 

  9. Ames, B.N., Shigenaga, M.K. and Hagen, T.M. Oxidants, antioxidants, and the degenerative diseases of aging. Proc. Natl. Acad. Sci. 90, 7915–7922 (1993).

    Article  PubMed  CAS  Google Scholar 

  10. Ames, B.N. Dietary carcinogens and anticarcinogens: oxygen radicals and degenerative diseases. Science 221, 1256–1264 (1983).

    Article  PubMed  CAS  Google Scholar 

  11. Morse, M. A. and Stone, G. D. Cancer chemoprevention: principles and prospects. Carcinogenesis 14, 1737–1746 (1993).

    Article  PubMed  CAS  Google Scholar 

  12. Mukhtar, H., Katiyar, S.K. and Agarwal, R. Green tea and skin-anticarcinogenic effects. J. Inv. Dermatol. 102, 3–7 (1994).

    Article  CAS  Google Scholar 

  13. Wattenberg, L.W. Chemoprevention of cancer. Cancer Res. 45, 1–8 (1985).

    Article  PubMed  CAS  Google Scholar 

  14. Wattenberg, L.W. Inhibition of carcinogenesis by minor anutrient constituents of the diet. Proc. Nutr. Soc. 49, 173–183 (1990).

    Article  PubMed  CAS  Google Scholar 

  15. Prestera, T., Holtzclaw, W.D., Zhang, Y. and Talalay, P. Chemical and molecular regulation of enzymes that detoxify carcinogens. Proc. Natl. Acad. Sci. 90, 2965–2969 (1993).

    Article  PubMed  CAS  Google Scholar 

  16. Miller, E.C., Miller, J.A., Brown, R.R. and MacDonald, J.C. On protective action of certain polycyclic aromatic hydrocarbons against carcinogenesis by aminoazo dyes and acetylaminofluorene. Cancer Res. 18, 469–473 (1958).

    PubMed  CAS  Google Scholar 

  17. Harris, C.C. p53: at the crossroads of molecular carcinogenesis and risk assessment. Science 262, 1980–1982 (1993).

    Article  PubMed  CAS  Google Scholar 

  18. Rahimtula, A.D., Zachariah, P.K. and O’Brien, P.J. The effects of antioxidants on the metabolism and mutagenicity of benzo(a)pyrene in vitro. Biochem. J. 164, 473–475 (1977).

    PubMed  CAS  Google Scholar 

  19. Rahimtula, A.D., Zachariah, P.K. and O’Brien, P.J. Differential effects of antioxidants on benzo(a)pyrene-3 hydroxylase activity in various tissues of rat. Br. J. Cancer 40, 105–112 (1979).

    Article  PubMed  CAS  Google Scholar 

  20. Rahimtula, A.D., Jernstrom, B., Dock, L. and Moldeus, P. Effects of dietary and in vitro 2-t butylhydroxyanisole and other phenols on hepatic enzyme activities in mice. Br. J. Cancer. 45, 935–944 (1982).

    Article  PubMed  CAS  Google Scholar 

  21. Prochaska, H.J. and Talalay, P. Regulatory mechanisms of monofunctional and bifunctional anticarcinogenic enzyme inducers in murine liver. Cancer Res. 48, 4776–4782 (1988).

    PubMed  CAS  Google Scholar 

  22. Egner, P.A., Kensler, T.W., Prestera, T., Talalay, P., Libby, A.H. and Curphay, T.J. Regulation of phase 2 enzyme induction by oltipraz and other dithiolethiones. Carcinog. 15, 177–181 (1994).

    Article  CAS  Google Scholar 

  23. Zhang, Y., Talalay, P., Cho, C.G. and Posner, G.H. A major inducer of anticarcinogenic protective enzymes from broccoli: isolation and elucidation of structure. Proc. Natl. Acad. Sci. 89, 2399–2403 (1992).

    Article  PubMed  CAS  Google Scholar 

  24. Haber, D., Siess, M.H., Waziers, I., Beaune, P. and Suschetet, M. Modification of hepatic drug metabolizing enzymes in rats fed naturally occurring allyl sulfides. Xenobiotica 24, 169–182 (1994).

    Article  PubMed  CAS  Google Scholar 

  25. Bjeldanes, L.F., Kim, J., Grose, K.R., Bartholomew, J.C. and Bradfield, C.A. Aromatic hydrocarbon responsiveness receptor agonists generated from indole-3-carbinol in vitro and in vivo: comparisons with tetrachlorobenzodioxin. Proc. Natl. Acad. Sci. 88, 9543–9547 (1991).

    Article  PubMed  CAS  Google Scholar 

  26. Cha, Y. and Heine, H.S. Comparative effects of dietary administration of butylhydroxyanisole and butylhydroxytoluene on several hepatic enzyme activities in mice and rats. Cancer Res. 42, 2609–2615 (1982).

    PubMed  CAS  Google Scholar 

  27. Guo, Z., Smith, T.J., Wang, E., Thomas, P.E. and Yang, C.S. Effects of phenethyl isothiocyanate, a carcinogenesis inhibitor, on xenobiotic metabolising enzymes and nitrosamine metabolism in rats. Carcinog. 13, 2205–2210 (1992).

    Article  CAS  Google Scholar 

  28. Putt, D.A., Kensler, T. and Hollenberg, P. Effects of three chemoprotective antioxidants, ethoxyquin, oltipraz and 1,2 dithiole-3-thione on cytochrome P-450 levels and aflatoxin ß, metabolism. FASEB J. 5, A1517 (1991).

    Google Scholar 

  29. Chae, Y., Ho, D.K., Cassady, J.M., Cook, V.M., Craig, B.M. and Baird, W.M. Effects of synthetic and naturally occurring flavonoids on metabolic activation of benzo(a)pyrene in hamster embryo cell cultures. Chem.-Biol. Interacns. 82, 181–193 (1992).

    Article  CAS  Google Scholar 

  30. Mukhtar, H. Das, M., Khan, W., Wang, Z.Y., Bik, D.P. and Bickers, D. Exceptional activity of tannic acids among naturally occurring plant phenols in protecting against dimethylbenzanthracene, benzopyrene, 3 methylcholanthrene induced skin tumorigenesis in mice. Cancer Res. 48, 2361–2365 (1988).

    PubMed  CAS  Google Scholar 

  31. Verma, A.K., Johnson, J.A., Gould, M.N. and Tanner, M.A. Inhibition of dimethylbenzanthracene and N-nitrosomethylurea induced rat mammary cancer by dietary flavonol quercetin. Cancer Res. 48, 5754–5761 (1988).

    PubMed  CAS  Google Scholar 

  32. Chae, Y.H., Marcus, C.B., Ho, D.K., Cassady, J.M. and Baird, W.M. Effects of synthetic and naturally occurring flavonoids on benzopyrene metabolism by hepatic microsomes. Cancer Lett. 60, 15–24 (1991).

    Article  PubMed  CAS  Google Scholar 

  33. Shah, G.M. and Bhattacharya, R.K. Modulation by plant flavonoids and related phenolics of microsome catalysed adduct formation between benzo(a)pyrene and DNA. Chem.-Biol. Interacns. 59, 1–15 (1986).

    Article  CAS  Google Scholar 

  34. Siess, N.H. and Vernevaut, M.F. The influence of food flavonoids on the activity of some hepatic microsomal monooxygenases in rats. Fd. Chem. Toxic. 20, 883–886 (1982).

    Article  CAS  Google Scholar 

  35. Beyeler, S., Testa, B. and Perrissoud, D. Flavonoids as inhibitors of rat liver monooxy-genase activities. Biochem. Pharmacol. 37, 1971–1979 (1988).

    Article  PubMed  CAS  Google Scholar 

  36. Steele, C.M., Lalies, M. and Ioannides, C. Inhibition of the mutagenicity of aromatic amines by the plant flavonoid(+)-catechin. Cancer Res. 45, 3573–3577 (1985).

    PubMed  CAS  Google Scholar 

  37. Das, M., Khan, W.A., Asokan, P., Bickers, D.R. and Mukhtar, H. Inhibition of epidermal xenobiotic metabolism in mice by naturally occurring plant phenols. Cancer Res. 47, 760–766 (1987).

    PubMed  CAS  Google Scholar 

  38. Chang, R.L., Huang, M.T., Wood, A.W., Wong, C.Q., Newmark, H.L., Yagi, H., Sayer, J.M., Jerina, D.M. and Conney, A.H. Effect of ellagic acid and hydroxylated flavonoids on the tumorigenicity of benzo(a)pyrene on mouse skin. Carcinog. 6, 1127–1133 (1985).

    Article  CAS  Google Scholar 

  39. Sayer, J.M., Whalen, D.L. and Jerina, D.M. Chemical strategies for the inactivation of bayregion diol epoxides. Drug. Metab. Rev. 20, 155–182 (1989).

    Article  PubMed  CAS  Google Scholar 

  40. Zhang, Z., Hamilton, S.M., Stewart, C., Strothers, A. and Teel, R.W. Inhibition of liver microsomal cytochrome P450 activity and metabolism of the tobacco specific nitrosamine NNK by ellagic acid. Anticancer Res. 13, 2341–2346 (1993).

    PubMed  CAS  Google Scholar 

  41. Das, M., Bickers, D.R. and Mukhtar, H. Effect of ellagic acid on hepatic and pulmonary xenobiotic metabolism in mice: studies on the mechanism of its anticarcinogenic action. Carcinog. 6, 1409–1413 (1985).

    Article  CAS  Google Scholar 

  42. Agarwal, R., Wang, Z.Y., Bik, D.P. and Mukhtar, H. Nordihydroguaiaretic acid, an inhibitor of lipoxygenase, also inhibits cytochrome P450 mediated monooxygenase activity. Drug Metab. Disp. 19, 620–624 (1991).

    CAS  Google Scholar 

  43. Yang, C.S. and Strickhart, F.S. Inhibition of hepatic mixed function oxidase activity by propyl gallate. Biochem. Pharmacol. 23, 3129–3138 (1974).

    Article  PubMed  CAS  Google Scholar 

  44. Hong, J., Wang, Z., Smith, T.J., Zhou, S., Shi, S., Pan, J. and Yang, C.S. Inhibitory effects of diallyl sulfide on the metabolism and tumorigenicity of the tobacco specific carcinogen 4-(methylnitrosamino)-l-(3 pyridyl)-l-butanone in A/J mouse lung. Carcinogenesis 13, 901–904 (1992).

    Article  PubMed  CAS  Google Scholar 

  45. Liu, L. and Castonguay, A. Inhibition of the metabolism and genotoxicity of 4 methyl-nitrosamino pyridyl butanone in rat hepatocytes by catechin. Carcinog. 12, 1203–1208 (1991).

    Article  CAS  Google Scholar 

  46. Castonguay, A., Allaire, L., Charest, M., Rossignol, G., and Boutet, M. Metabolism of methylnitrosamino-l-(3 pyridyl)-1 butanone by hamster respiratory tissues cultured with ellagic acid. Cancer Lett., 46, 93 (1989); for errata, see 47, 161.

    Article  PubMed  CAS  Google Scholar 

  47. Barch, D.H. and Fox, C.C. Dietary ellagic acid reduces the esophageal microsomal metabolism of methylbenzylnitrosamine. Cancer Lett. 44, 39–44 (1989).

    Article  PubMed  CAS  Google Scholar 

  48. You, W., Blot, W., Chang, A.E., Yang, Z.T., Qi, A., Henderson, B.E., Fraumeni, J.F., Wang, T. Allium vegetables and reduced risk of stomach cancer. JNCI 81, 162–164 (1989).

    Article  PubMed  CAS  Google Scholar 

  49. Pan, J., Hong, J.Y., Ma, B.L., Ning, S.M., Paranawithana, S.R. and Yang, C.S. Transcriptional activation of cytochrome P450 2B1/2 genes in rat liver by diallyl sulfide, a compound derived from garlic. Arch. Biochem. Biophys. 302, 337–342 (1993).

    Article  PubMed  CAS  Google Scholar 

  50. Vang, O., Jensen, H. and Autrup, H. Induction of cytochrome P450 1A1, 1A2, 2B1, 2B2 and 2E1 by broccoli in rat liver and colon. Chem. Biol. Interacns. 78, 85–96 (1991).

    Article  CAS  Google Scholar 

  51. Wortelboer, H.M., De Kruif, C.A., Iersel, A.A., Noordhoek, J., Blaauboer, B., Van Bladeren, P.J. and Falke, H.E. Effects of cooked brussel sprouts on cytochrome P450 profile and phase II enzymes in rat. Fd. Chem. Toxic. 30, 17–27 (1992).

    Article  CAS  Google Scholar 

  52. Ishizaki, H., Brady, J.F., Ning, S.M. and Yang, C.S. Effect of phenethyl isothiocyanate on microsomal N-nitrosodimethylamine metabolism and other monooxygenase activities. Xenobiotica 20, 255–264 (1990).

    Article  PubMed  CAS  Google Scholar 

  53. Salbe, A.D., and Bjeldanes, L.F. Effect of diet on the DNA binding of aflatoxin B1 in the rat. Carcinogenesis 10, 629–634 (1989).

    Article  PubMed  CAS  Google Scholar 

  54. Tanaka, T., Mori, Y., Morishita, Y., Hara, A., Ohno, T., Kojima, T. and Mori, H. Inhibitory effect of sinigrin and indolecarbinol on diethylnitrosamine-induced hepatocarcinogenesis in male rats. Carcinogenesis 11, 1403–1406 (1990).

    Article  PubMed  CAS  Google Scholar 

  55. Wortelboer, H.M., Kruif, C.A., Falke, H.E., Noordhoek, J. and Blaauboer, B.J. Acid reacton products of indole carbinol and their effects on cytochrome P450 and phase II enzymes in hepatocytes. Biochem. Pharmacol. 43, 1439–1447 (1992).

    Article  PubMed  CAS  Google Scholar 

  56. Wattenberg, L.W. and Bueding, E. Inhibitory effects of oltipraz on carcinogenesis induced by benzo(a)pyrene and diethylnitrosamine. Carcinogenesis 7, 1379–1381 (1986).

    Article  PubMed  CAS  Google Scholar 

  57. Kensler, T.W., Groopman, J.D., Eaton, D.L., Curphey, T. and Roebuck, B. Potent inhibition of aflatoxin induced hepatic tumorigenesis by the monofuctional enzyme inducer 1,2 dithiole-3-thione. Carcinogenesis 13, 95–100 (1992).

    Article  PubMed  CAS  Google Scholar 

  58. Eling, T.E. and Curtis, J.F. Hydroperoxide-dependent oxidation. Pharmacol. Ther. 53, 261 (1993).

    Article  Google Scholar 

  59. Sarkar, F.H., Radcliff, G. and Callewaert, D.M. Purified prostaglandin synthase activates aromatic amines to mutagenic derivatives. Mutn. Res. 282, 273–281 (1992).

    Article  CAS  Google Scholar 

  60. Pruess-Schwartz, D., Nimesheim, A. and Marnett, L.J. Peroxyl radical and cytochrome P-450 metabolic activation of 7,8 dihydroxy 7,8 dihydrobenzo(a)pyrene in mouse skin in vitro and in vivo. Cancer Res. 49, 1732–1737 (1989).

    PubMed  CAS  Google Scholar 

  61. Zenser, T.V. and Davis, B.B. Arachidonic acid metabolism by human urothelial cells: implications in aromatic amine-induced bladder cancer. Prostaglandins Leuk. Essent. Fatty Acids: Rev. 31: 199–207 (1988).

    CAS  Google Scholar 

  62. Yamazoe, Y., Zenser, T.V., Miller, D.W. and Kadlubar, F.F. Mechanism of formation and structural characterisation of DNA adducts derived from peroxidative activation of benzidine. Carcinogen. 9, 1635–1641 (1988).

    Article  CAS  Google Scholar 

  63. Krauss, R.S., Angerman-Stewart, J., Dooley, K.L., Kadlubar, F.F. and Eling, T.E. The formation of 2 aminofluorene-DNA in vivo: evidence for peroxidase-mediated activation. Biochem. Toxicol. 4, 111–117 (1989).

    Article  CAS  Google Scholar 

  64. Josephy, P.D., Chiu, A.I.H. and Eling, T.E. Prostaglandin H synthase dependent mutagenic activation of benzidine in a Styphimunium Ames tester strain possesing elevated N-acetyltransferase levels Cancer Res. 49, 853–856 (1989).

    PubMed  CAS  Google Scholar 

  65. Majid, S., Kharduja, K., Gandhi, R.K., Kapus, S. and Sharma, R.R. Influence of ellagic acid on antioxidant defense system and lipid peroxidation in mice. Biochem. Pharmacol. 42, 1441–1445 (1991).

    Article  PubMed  CAS  Google Scholar 

  66. Marnett, L.J., Reed, G.A. and Johnson, J.T. Prostaglandin synthetase dependent benzo(a)pyrene oxidation: products of the oxidation and inhibition of their formation by antioxidants. Biochem. biophys. Res. Comm. 79, 569–576 (1977).

    Article  PubMed  CAS  Google Scholar 

  67. O’Brien, P.J. Radical formation during the peroxidase catalyzed metabolism of carcinogens and xenobiotics: the reactivity of these radicals with GSH, DNA and unsaturated lipid. Free Radic. Biol. Med. 4, 169–183 (1988).

    Article  PubMed  Google Scholar 

  68. Tsuruta, Y., Subrahmanyan, V.V., Marshall, W. and O’Brien, P.J. Peroxidase mediated irreversible binding of aryamine carcinnogens to DNA in intact polymorphonuclear leukocytes activated by a tumor promoter. Chemico-Biol. Interacns. 53, 25–35 (1985).

    Article  CAS  Google Scholar 

  69. Uetrecht, J.P. The role of leukocyte-generated reactive metabolites in the pathogenesis of idiosyncratic drug reactions. Drug Metab. Rev. 24, 299–366 (1992).

    Article  PubMed  CAS  Google Scholar 

  70. Cross, A.R. Inhibitors of the leukocyte superoxide generating oxidase. Free Rad. Biol. Med. 8, 71–93 (1990).

    Article  PubMed  CAS  Google Scholar 

  71. Chena, K.C., Cahill, D.S., Kasai, H., Nishimura, S., and Loeb, L.A. 8 hydroxydeoxy-guanosine, an abundant form of oxidative DNA damage causes G-T and A-T substitution. J. Biol. Chem. 267, 166–172 (1992).

    Google Scholar 

  72. Kensler, T. W., Bush, D.M. and Kozumbo, W.J. Inhibition of tumor promotion by a biomimetic superoxide dismutase. Science 221, 75–77 (1983).

    Article  PubMed  CAS  Google Scholar 

  73. Kasai, H., Okada, Y., Nishimura, S., Rao, M.S., and Reddy, J.K. Formation of 8-hydroxydeoxyguanosine in rat kidney DNA after intraperitoneal administration of ferric nitrilotriacetate. Carcinogenesis 11, 345–347 (1989).

    Google Scholar 

  74. Hinrichsen, L.I., Floyd, R.A. and Sudilovsky, O. Is 8 hydroxydeoxyguanosine a mediator of carcinogenesis by choline-devoid diet in the rat liver? Carcinogenesis 11, 1879–1881 (1990).

    Article  PubMed  CAS  Google Scholar 

  75. Kasai, H., Nishimura, S., Kurokawa, Y., and Hayoslii, Y. Oral administration of the renal carcinogen, potassium bromate, specifically produces 8-hydroxydeoxyguanosine in rat target organ DNA. Carcinogenesis, 8, 1959–1961 (1987).

    Article  PubMed  CAS  Google Scholar 

  76. Umemura, T., Sai, K., Takagi, A., Hasegawa, R. and Kurokawa, Y. Formation of 8-hydroxydeoxyguanosine in rat kidney DNA after intraperitoneal administration of ferric nitrilotriacetate. Carcinogenesis 11, 345–347 (1990).

    Article  PubMed  CAS  Google Scholar 

  77. Tchou, J., and Grollman, A.P. Repair of DNA containing the oxidatively damaged base, 8 oxyguanine. Mutn. Res. 299, 277–287 (1993).

    Article  CAS  Google Scholar 

  78. Slaga, T.J., Fischer, S.M., Weeks, C.E., Nelson, K., Mamrack, M. and Klein-Szanto, A.J.P. Specificity and mechanism(s) of promoter inhibitors in multistage promotion. In: Carcinogenesis, Vol. 7, pp. 19–34, Hecker, E., Kuntz, W., Fusenig, N.E., Marks, F. and Thielmann, H.W. (eds) Raven Press, New York (1982).

    Google Scholar 

  79. Athar, M., Raza, H., Bickers, D.M. and Muktar, H. Inhibition of benzoyl peroxide mediated tumor promotion in 1,2 dimethylbenz(a)anthracene-initiated skin of Sencar mice by antioxidants, nordihydroguaiaretic acid and diallyl sulfide. J. Invest. Dermatol., 94, 162 (1990).

    Article  PubMed  CAS  Google Scholar 

  80. Huang, M.T., Smart, R.C., Wong, C.Q., Conney, A.H. Inhibitory effect of curcumin, chlorogenic acid, caffeic acid, ferulic acid on tumor promotion in mouse skin by tetradecanoylphorbol acetate. Cancer Res. 48, 5941–5946 (1988).

    PubMed  CAS  Google Scholar 

  81. Rao, M.S., Lalwani, N.D., Watanabe, T.K. and Reddy, J.K. Inhibitory effects of antioxidants ethoxyquin and butylhydroxyanisole on hepatic tumorigenesis in rats fed ciprofibrate, a peroxisome proliferator. Cancer Res. 44, 1072–1076 (1984).

    PubMed  CAS  Google Scholar 

  82. Ghoshal, A.K., Rushmore, T.H., Calderon, P., Roberfroid, M. and Farber, E. Prevention by a free radical scavenger of prooxidant effects of choline deficiency. Free Rad. Biol. Med. 8, 3–7 (1990).

    Article  PubMed  CAS  Google Scholar 

  83. Okada, S., Hamazaki, S., Ebina, Y., Li, J.L. and Midorikawa, O. Nephrotoxicity and its prevention by vitamin E in ferric nitrilotriacetate-promoted lipid peroxidation. Biochim. biophys. Acta 922, 28–33 (1987).

    Article  PubMed  CAS  Google Scholar 

  84. Tanaka, T., Kojima, T., Kawamori, T., Wang, A., Suzui, M., Okamoto, K. and Mori, H. Inhibition of 4 nitroquinoline 1 oxide induced rat tongue carcinogenesis by the naturally occurring plant phenolics caffeic, ellagic, chlorogenic and ferulic acids. Carcinogenesis 14, 1321–1325 (1993).

    Article  PubMed  CAS  Google Scholar 

  85. Nunoshiba, T., and Demple, B. Potent intracellular oxidative stress exerted by the carcinogen 4 nitroquinoline N oxide. Cancer Res. 53, 3250–3252 (1993).

    PubMed  CAS  Google Scholar 

  86. Wargowich, M. J., Imada, O. and Stephens, L.C. Initiation and post initiation chemopreventive effects of diallyl sulfide in oesophageal carcinogenesis. Cancer Lett. 64, 39–42 (1992).

    Article  Google Scholar 

  87. Cerutti, P.A. Oxidant stress and carcinogenesis. Eur. J. Clin. Invest. 21, 1–5 (1991).

    Article  PubMed  CAS  Google Scholar 

  88. Keller, B.J., Marsman, D.S.O., Popp, J.A., Thyman, R.G. Several nongenotoxic carcinogens uncouple mitochondrial oxidative phosphorylation. Biochim. biophys. Acta 1162, 237 (1992).

    Article  Google Scholar 

  89. Monteiro, H.P., Ivaschenko, Y., Fischer, R. and Stern, A. Inhibition of protein tyrosine phosphatase activity by diamide is reversed by epidermal growth factor in fibroblasts. FEBS Lett. 295, 146–148 (1991).

    Article  PubMed  CAS  Google Scholar 

  90. Milo, G.E., Kurican, P., Kirsten, E. and Kun, E. Inhibition of carcinogen-induced cellular transformation of human fibroblasts by drugs that interact with the poly(ADP-ribose) polymerase system. FEBS Lett. 179, 332–336 (1985).

    Article  PubMed  CAS  Google Scholar 

  91. Yamamoto, S. and Kyoto, R. Inhibitors of the arachidonic acid cascade and their chemoprevention of skin cancer, in Cancer Chemoprevention. Ed Wattenberg, L., Lipkin, M., Boone, C.W. and Keloff, G.J. pp 141–151, CRC press (1992).

    Google Scholar 

  92. Marnett, L.J. Aspirin and the potential role of prostaglandins in colon cancer. Cancer Res. 52, 5575–5589 (1992).

    PubMed  CAS  Google Scholar 

  93. Reddy, B.S. Inhibitors of the arachidonic acid cascade and their chemoprevention of colon carcinogenesis, in Cancer Chemoprevention. Ed. Wattenberg, L., Lipkin, M., Boone, C.W. and Kelopff, G.J. pp. 153–163, CRC Press (1992).

    Google Scholar 

  94. Nguyen, T. and Pickett, C.B. Regulation of rat glutathione S transferase Ya subunit gene expression. J. Biol. Chem. 267, 1535–13539 (1992).

    Google Scholar 

  95. Prestera, T., Holtzclaw, Zhang, Y. and Talalay, P. Chemical and molecular regulation of enzymes that detoxify carcinogens. Proc. Natl. Acad. Sci. 90, 2965–2969 (1993).

    Article  PubMed  CAS  Google Scholar 

  96. Li, Y. and Jaiswal, A.K. Regulation of human NAD(P)H: quinone oxidoreductase gene: role of AP1 binding site contained within human antioxidant responsive element. J. Biol. Chem. 267, 15097–15104 (1992).

    PubMed  CAS  Google Scholar 

  97. Prestera, T., Zhang, Y., Spencer, S.R., Wilczak, C.A. and Talalay, P. The electrophile counterattack response: protection against neoplasia and toxicity. Adv. Enz. Regul. 33, 281–296 (1993).

    Article  CAS  Google Scholar 

  98. DeLong, M.J., Dolan, P., Santamaria, A. and Bueding, E. Dithiolethione analogs: effects on NAD(P)H quinone reductase and glutathione levels in murine hepatoma cells. Carcinog. 7, 977–980 (1986).

    Article  CAS  Google Scholar 

  99. Morel, F., Fardel, O., Meyer, D.J., Kensler, T.W., Ketterer, B. and Guillouzo, A. Preferential increase of GS transferase class α-transcripts in cultured human hepatocytes by phenobarbital, methylcholanthrene and dithiolethiones. Cancer Res. 53, 231–234 (1993).

    PubMed  CAS  Google Scholar 

  100. Munday, R. and Winterbourn, C.C. Reduced glutathione in combination with superoxide dismutase as an important biological antioxidant defense mechanism. Biochem. Pharmacol. 38, 4349–4352 (1989).

    Article  PubMed  CAS  Google Scholar 

  101. Keyse, S.M. and Tyrrell, R.M. Both near ultraviolet radiation and the oxidising agent hydrogen peroxide induced a 32KDa stress protein in normal human skin fibroblasts. J. Biol. Chem. 262, 14821–14825 (1987).

    PubMed  CAS  Google Scholar 

  102. Cantoni, A., Guidarelli, O., Sestili, P., Mannello, F., Gazzanelli, G. and Cattabeni, F. Development and characterization of hydrogen peroxide resistant Chinese hamster ovary cell variants. Biochem. Pharmacol. 45, 2251–2257 (1993).

    Article  PubMed  CAS  Google Scholar 

  103. Spitz, D.R., Adams, D.T., Sherman, C.M. and Roberts, R.J. Mechanisms of cellular resistance to hydrogen peroxide, hyperoxia and 4 hydroxy 2 nonenal toxicity: the significance of increased catalase activity in H2O2 resistant fibroblasts. Arch. Biochem. Biophys. 292, 221–227 (1992).

    Article  PubMed  CAS  Google Scholar 

  104. Spitz, D.R., Sullivan, S.J., Malcom, R.R., and Roberts, R.J. Glutathione dependent metabolism and detoxification of 4 hydroxy 2 nonenal. Free Rad. Biol. Med. 11, 415–423 (1991).

    Article  PubMed  CAS  Google Scholar 

  105. Chu, F.F., Esworthy, R.S., Aleman, S. and Dorshow, J.H. Modulation of glutathione peroxidase expression by selenium. Nucl. Acid. Res. 18, 1531–1539 (1990).

    Article  CAS  Google Scholar 

  106. Sandstrom, B., Carlsson, J. and Marklund, S.L. Selenite-induced variation in glutathione peroxidase activity of three mammalian cell lines. Radiation Res. 117, 318–325 (1989).

    Article  PubMed  CAS  Google Scholar 

  107. Bannai, S., Sato, H., Ishii, T. and Taketani, S. Enhancement of glutathione levels in mouse peritoneal macrophages. Biochim. biophys. Acta. 1092, 175–179 (1991)

    Article  PubMed  CAS  Google Scholar 

  108. Deneke, S.M. and Fanburg, B.L. Regulation of cellular glutathione Am. J. Physiol. 257, L163–L173 (1989).

    PubMed  CAS  Google Scholar 

  109. Taketani, S., Sato, H., Yoshinaga, T., Tokunaga, R., Ishii, T., and Bannai, S. Induction in mouse peritoneal macrophages of 34kDa stress protein and heme oxygenase by sulfhydryl-reactive agents. J. Biochem. 108, 111–115 (1990).

    Google Scholar 

  110. Mimnaugh, E.G., Dusre, L., Atwell, J. and Myers, C.E. Differential oxygen radical susceptibility of adriamycin-sensitive and-resistant human breast tumor cells. Cancer Res. 49, 8–15 (1989).

    PubMed  CAS  Google Scholar 

  111. Sinha, B.K., Minnaugh, E.C., Rajagopalan, S. and Myers, C.E. Adriamycin activation and oxygen free radical formation in human breast tumor cells. Cancer Res. 49, 3844–3848 (1989).

    PubMed  CAS  Google Scholar 

  112. Meier-Bratschi, A., Lutz, W.K. and Schlatter, C. Methylation of liver DNA of a rat and mouse by N-nitrosodimethylamine formed in vivo from dimethylamine and nitrite. Food Chem. Toxicol. 21, 285–290 (1983).

    Article  PubMed  CAS  Google Scholar 

  113. Astili, B.D. and Mulligan, L.T. Phenolic antioxidants and the inhibition of hepatotoxicity from N-dimethylnitrosamine formed in situ in the rat stomach. Fd. Cosmet. Toxicol. 15, 167–171 (1977).

    Article  Google Scholar 

  114. Stich, H.F., Dunn, B.P., Pignatelli, B., Ohshinia, H. and Bartsch, H. Dietary phenolics and betel nut extracts as modifiers of N-nitrosation in rat and man. IARC Sc. Publ. 57, 213–222 (1984).

    CAS  Google Scholar 

  115. Pignatelli, B., Bereziat J., Descotes, G. and Bartsch, H. Catalysis of nitrosation in vivo in rats by catechin and resorcinol and inhibition by chlorogenic acid. Carcinogenesis 3, 1045–1049 (1982).

    Article  PubMed  CAS  Google Scholar 

  116. Kuenzig W., Chan, J., Norkus, E., Newmark, H., Mergens, W. and Conney, A.H. Caffeic acid and ferulic acid as blockers of nitrosamine formation. Carcinogenesis 5, 309–313 (1984).

    Article  PubMed  CAS  Google Scholar 

  117. Nguyen, T., Brunson, D., Crespi, C.L., Periman, B.W., Wishnok, J.S. and Tannenbaum, S.R. DNA damage and mutation in human cells exposed to nitric oxide in vitro. Proc. Natl. Acad. Sci. 89, 3030–3034 (1992).

    Article  PubMed  CAS  Google Scholar 

  118. Carreras, M.C., Paragament, G.A., Catz, S.D., Poderoso, J.J. and Boveris, A. Kinetics of nitric oxide and hydrogen peroxide production and formation of peroxynitrite during the respiration burst of human neutrophils. FEBS Lett. 341, 65–68 (1994).

    Article  PubMed  CAS  Google Scholar 

  119. Michnovicz, J.J., Bradlow, H.L. Induction of estradiol metabolism by dietary indole-1-carbinol in humans. J. Natl. Cancer Inst. 82, 947–949 (1990).

    Article  PubMed  CAS  Google Scholar 

  120. Baldwin, W.S. and Leblanc, G.A. The anticarcinogenic plant compound indolecarbinol differentially modulates P450-mediated steroid hydroxylase activities in mice. Chem.-Biol. Interacns. 83, 155–169 (1992).

    Article  CAS  Google Scholar 

  121. Bradlow, H.L., Michnovicz, J.J., Telang, N.T. and Osborne, M.P. Effects of dietary indole-3-carbinol on estradiol metabolism and spontaneous mammary tumors in mice. Carcinogenesis 12, 1571–1574 (1991).

    Article  PubMed  CAS  Google Scholar 

  122. Takahashi, S., Hakoi, K., Yaga, H., Hirose, M., Ito, N. and Fukushima, S. Enhancing effects of diallyl sulfide on hepatocarcinogenesis and inhibitory actions of the related diallyl disulfide on colon and renal carcinogenesis in rats. Carcinogenesis 13, 1513–1518 (1992).

    Article  PubMed  CAS  Google Scholar 

  123. Bailey, G.S., Hendricks, J.D., Shelton, D.W. Enhancement of carcinogenesis by the natural anticarcinogenindole-3-carbinol. J. Natl. Cancer Inst. 78, 931–934 (1987).

    PubMed  CAS  Google Scholar 

  124. Ito, N. and Hirose, M. Antioxidants-carcinogenic and chemopreventive properties. Adv. Cancer Res. 53, 247–302 (1989).

    Article  PubMed  CAS  Google Scholar 

  125. Farber, E. Clonal adaptation during carcinogenesis. Biochem. Pharmacol. 39, 1837–1846 (1990).

    Article  PubMed  CAS  Google Scholar 

  126. Jones, G.R.N. Cancer destruction in vivo through disrupted energy metabolism. Physiol. Chem. Phys. and Med. NMR 24, 181–194 (1992).

    CAS  Google Scholar 

  127. De Vries, C.E. and Van Noorden, C.J.F. Effects of fatty acids on tumor growth and metastasis. Anticancer Res. 12, 1513–1522 (1992).

    PubMed  Google Scholar 

  128. Corrocher, R., Casaril, M., Bellisola, G., Gabrielli, G.B., Guidi, G.C. and DeSandre, G. Severe impairment of antioxidant systems in human hepatoma. Cancer 58, 1658–1662 (1986).

    Article  PubMed  CAS  Google Scholar 

  129. Canuto, R.A.,, Muzio, G., Biocca, M.E. and Dianzani, M.U. Lipid peroxidation in rat AH-130 hepatoma cells enriched in vitro with arachidonic acid. Cancer Res. 51, 4603–4608 (1991).

    PubMed  CAS  Google Scholar 

  130. Cogrel, P., Morel, I., Lescoat, G., Chevanne, M., Brissot, P., Cillard, P. and Cillard, J. The relationship between fatty acid peroxidation and α-tocopherol consumption in isolated normal and transformed hepatocytes. Lipids 28, 115–119 (1993).

    Article  PubMed  CAS  Google Scholar 

  131. Kandaswami, C., Perkins, E., Soloniuk, D.S. and Middleton, E. Differential inhibition of proliferation of human squamous cell carcinoma, gliosarcoma and embryonic fibroblastlike lung cells in culture by plant flavonoids. Anti-Cancer Drugs 3, 525–530 (1992).

    Article  PubMed  CAS  Google Scholar 

  132. Khan, S., Ramuvani, J.J. and O’Brien, P.J. The toxicity of mechlorethamine and other alkylating anti-cancer drugs: role of lipid peroxidation. Biochem. Pharmacol. 43, 1963–1967 (1992).

    Article  PubMed  CAS  Google Scholar 

  133. Powis, G. and Hacker, M.P. The toxicity of anticancer drugs. Pergamon Press (1991).

    Google Scholar 

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O’Brien, P.J. (1994). Antioxidants and Cancer: Molecular Mechanisms. In: Armstrong, D. (eds) Free Radicals in Diagnostic Medicine. Advances in Experimental Medicine and Biology, vol 366. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1833-4_16

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