Nonnutritive Components in Foods as Modifiers of the Cancer Process

  • John A. Milner
Part of the Nutrition ◊ and ◊ Health book series (NH)


Cancer, once thought to be an inevitable consequence of aging, is now thought to be primarily associated with a host of environmental factors, including dietary habits (1). Changes in cancer death rates during relatively short periods of time indicate that environmental factors, rather than a genetic predisposition, are primary determinants of risk. Since evidence exists that environmental factors correlate with approx 90% of all cancer cases, it becomes of paramount importance to identify those factors of greatest importance (1). Within the many possible factors, dietary practice is one that likely deserves special attention (1,2). Dietary habits have been correlated with 60% of cancers in women and more than 40% in men. Geographic correlations of per capita intake of fruits and vegetables are routinely, although not universally, observed to be inversely related to cancer risk (3–10).


Ellagic Acid Diallyl Disulfide Garlic Powder Diallyl Sulfide Allyl Mercaptan 


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  1. 1.
    Raunio H, Husgafvel-Pursiainen K, Anttila S, Hietanen E, Hirvonen A, Pelkonen O. Diagnosis of polymorphisms in carcinogen-activating and inactivating enzymes and cancer susceptibility—a review. Gene 1995; 159:113–21.Google Scholar
  2. 2.
    Wynder EL, Gori GB. Contribution of the environment to cancer incidence: an epidemiologic exercise. J Natl Cancer Inst 1977; 58:825–832.Google Scholar
  3. 3.
    Steinmetz KA, Potter JD, Folsom AR. Vegetables, fruit, and lung cancer in the Iowa Women’s Health Study. Cancer Res 1993; 53:536–543.Google Scholar
  4. 4.
    Steinmetz KA. Kushi LH, Bostick RM, Folsom AR, Potter JD. Vegetables, fruit, and colon cancer in the Iowa Women’s Health Study. Am J Epidemiol1994: 139:1–15.Google Scholar
  5. 5.
    Block G. Dietary guidelines and the results of food consumption surveys. Amer J Clin Nutr 1991; 53:356S, 357S.Google Scholar
  6. 6.
    Serdula MK, Coates RJ, Byers T, Simoes E, Mokdad AH, Subar AF. Fruit and vegetable intake among adults in 16 states: results of a brief telephone survey. Am J Public Hlth 1995; 85:236–239.Google Scholar
  7. 7.
    Yu MW, Hsieh HH, Pan WH, Yang CS, Chen CJ. Vegetable consumption, serum retinol level, and risk of hepatocellular carcinoma. Cancer Res 1995; 55:1301–1305.Google Scholar
  8. 8.
    Landa MC, Frago N, Tres A. Diet and the risk of breast cancer in Spain. Eur J Cancer Prev 1994; 3:313–320.Google Scholar
  9. 9.
    Stavric B. Role of chemopreventers in human diet. Clin Biochem 1994; 27:319–332.Google Scholar
  10. 10.
    Kennedy AR. The evidence for soybean products as cancer preventive agents. J Nutr 1995; 125:733S–743S.Google Scholar
  11. 11.
    Yang CS. Wane ZY. Tea and cancer. J Natl Cancer Inst 1993; 85:1038–1049.Google Scholar
  12. 12.
    Jin ZC, Qian J. Inhibitory effects of fifteen kinds of Chinese herbal drugs, vegetables and chemicals on SOS resnonse. Chin J Prev Med 1994: 28:147–150.Google Scholar
  13. 13.
    Singletary KW, Nelshoppen J. Inhibition of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumorigenesis and in vivo formation of mammary DMBA-DNA adducts by rosemary extract. Cancer Lett 1991; 60:169–175.Google Scholar
  14. 14.
    Steinmetz KA, Potter JD. Food-group consumption and colon cancer in the Adelaide Case-Control Study. I. Vegetables and fruit. Food-group consumption and colon cancer in the Adelaide Case-Control. Int J Cancer 1993; 53:711–719.Google Scholar
  15. 15.
    Milner JA. Reducing the risk of cancer. In: Functional Foods. New York: Van Nostrand Reinhold, NY, 1994; 39–70.Google Scholar
  16. 16.
    Dorant E, van den Brandt PA, Goldbohm RA, Hermus RJ, Sturmans E Garlic and its significance for the prevention of cancer in humans: a critical view. Br J Cancer 1933; 67:424–429.Google Scholar
  17. 17.
    Jain AK, Vargas R, Gotzkowsky S, McMahon FG. Can garlic reduce levels of serum lipids? A controlled clinical study. Am J Med 1993; 94:632–635.Google Scholar
  18. 18.
    Mei X, Wang ML, Xu HX, et al. Garlic and gastric cancer I: the influence of garlic on the level of nitrate and nitrite in gastric juice. Acta Nutrimenta Sinica 1982; 4:53–56.Google Scholar
  19. 19.
    You WC, Blot WJ, Chang, YS, et al. Allium vegetables and reduced risk of stomach cancer. J Natl Cancer Inst 1989;81:162–164.Google Scholar
  20. 20.
    Mei X, Wang ML, Han N. Garlic and gastric cancer II-The inhibitory effect of garlic on the growth of nitrate reducing bacteria and on the production of nitrite. Acta Nutrimenta Sinica 1985;7:173–176.Google Scholar
  21. 21.
    Adetumbi MA, Lau BH. Allium sativum (garlic)-a natural antibiotic. Med Hypotheses 1983; 12:227–237.Google Scholar
  22. 22.
    Mei X, Lin X, Liu J, et al. The blocking effect of garlic on the formation of N-nitrosoproline in humans. Acta Nutrimenta Sinica 1989; 11:141–145.Google Scholar
  23. 23.
    Shenoy NR, Choughuley AS. Inhibitory effect of diet related sulphydryl compounds on the formation of carcinogenic nitrosamines. Cancer Lett 1992; 65:227–232.Google Scholar
  24. 24.
    Lin XY, Liu JZ, Milner JA. Dietary garlic suppresses DNA adducts caused by N-nitroso compounds. Carcinogenesis 1994: 15:349–352.Google Scholar
  25. 25.
    Liu JZ, Schaffer EM, Pegg AE, Milner JA. Dietary garlic inhibits mammary carcinogenesis induced by N-methylnitrosourea. FASEB J1995; 9:A991.Google Scholar
  26. 26.
    Block E. The organosulfur chemistry of the genus Allium-implications for the organic chemistry of sulfur. Angewandte Chemie Inter Ed Eng 1992; 31:1135–1178.Google Scholar
  27. 27.
    Liu JZ, Lin RI, Milner JA. Inhibition of 7,12-dimethylbenz(a)- anthracene induced mammary tumors and DNA adducts by garlic powder. Carcinogenesis 1992; 13:1847–1851.Google Scholar
  28. 28.
    Wargovich MJ, Woods C, Eng VWS, Stephens LC, Gray KN. Chemoprevention of nitrosomethylbenzylamine-induced esophageal cancer in rats by the thioether, diallyl sulfide. Cancer Res 1988; 48:6872–6875.Google Scholar
  29. 29.
    Sumiyoshi H, Wargovich MJ. Chemoprevention of 1,2-dimethylhydrazine-induced colon cancer in mice by natural occurring organosulfur compounds. Cancer Res 1990; 50:5084–5087.Google Scholar
  30. 30.
    Belman S. Onion and garlic oils inhibit tumor promotion. Carcinogenesis 1983; 4: 1063–1067.Google Scholar
  31. 31.
    Wattenberg LW, Spamins VL, Barany G. Inhibition of N-nitrosodiethylamine carcinogenesis in mice by naturally occurring organosulfur compounds and monoterpenes. Cancer Res 1989; 49:2689–2692.Google Scholar
  32. 32.
    Amagase H, Milner JA. Impact of various sources of garlic and their constituents on 7,12-dimethylbenz(a)-anthracene binding to mammary cell DNA. Carcinogenesis 1993; 14:1627–1631.Google Scholar
  33. 33.
    Brady JF, Wang MH, Hong JY, et al. Modulation of rat hepatic microsomal monooxygenase enzymes and cytotoxicity by diallyl sulfide. Toxic Appl Pharmacol 1991; 108:342–354.Google Scholar
  34. 34.
    Liu JZ, Lin XY, Milner JA. Dietary garlic powder increases glutathione content and glutathione S-transferase activity in rat liver and mammary tissues. FASEB J 1992; 6(4):A 1493.Google Scholar
  35. 35.
    Sparnins VL, Barany G, Wattenberg LW. Effects of organosulfur compounds from garlic and onions on benzo(a)pyrene-induced neoplasia and glutathione S-transferase activity in the mouse. Carcinogenesis 1988; 9:131–134.Google Scholar
  36. 36.
    Choy YM, Kwok TT, Fung KP, Lee CY. Effect of garlic, Chinese medicinal drugs and amino acids on growth of Erlich ascites tumor cells in mice. Amer J Chinese Med 1983; 11:69–73.Google Scholar
  37. 37.
    Sundaram SG, Milner JA. Impact of organosulfur compounds in garlic on canine mammary tumor cells in culture. Cancer Lett 1994: 74:85–90.Google Scholar
  38. 38.
    Sundaram SG, Milner JA. Diallyl disulfide inhibits the proliferation of human colon tumor cells in culture. Biochem Biophys Acta, 1996; 1315:15–20.Google Scholar
  39. 39.
    Sundaram SG, Milner JA. Diallyl disulfide suppresses the growth of human colon tumor cell xenographs in athymic nude mice. J Nutr 1996; 126:1355–1361.Google Scholar
  40. 40.
    Ip C, Lisk DJ, Stoewsand GS. Mammary cancer prevention by regular garlic and selenium-enriched garlic. Nutr Cancer 1992; 7:279–286.Google Scholar
  41. 41.
    Amagase H, Schaffer E, Milner JA. Dietary components modify the ability of garlic to suppress 7,12 dimethylbenz(a)anthracene-induced mammary DNA adducts. J Nutr 1996; 126:817–824.Google Scholar
  42. 42.
    Dorant E, van den Brandt PA, Goldbohm RA. A prospective cohort study on Allium vegetable consumption, garlic supplement use, and the risk of lung carcinoma in The Netherlands. Cancer Res 1994; 54:6148–6153.Google Scholar
  43. 43.
    Takada N, Kitano M, Chen T, Yano Y, Otani S, Fukushima S. Enhancing effects of organosulfur compounds from garlic and onions on hepatocarcinogenesis in rats: association with increased cell proliferation and elevated ornithine decarboxylase activity. Jpn J Cancer Res 1994; 85:1067–1072.Google Scholar
  44. 44.
    Matsuda T, Takada N, Yano Y, Wanibuchi H, Otani S, Fukushima S. Dose-dependent inhibition of glutathione S-transferase placental form-positive hepatocellular foci induction in the rat by methyl propyl disulfide and propylene sulfide from garlic and onions. Cancer Lett 1994; 86:229–234.Google Scholar
  45. 45.
    Apitz-Castro R, Cabrera S, Cruz MR, Ledezma E, Jain MK. Effects of garlic extract and of three pure components isolated from it on human platelet aggregation, arachidonate metabolism, release reaction and platelet ultrastructure. Thromb Res 1983; 32:155–169.Google Scholar
  46. 46.
    Srivastava KC, Tyagi OD. Effects of a garlic-derived principle (ajoene) on aggregation and arachidonic acid metabolism in human blood platelets. Prost Leuk Essen Fatty Acids 1993; 49:587–595.Google Scholar
  47. 47.
    Beecher CW. Cancer preventive properties of varieties of Brassica oleracea: a review. Amer J Clin Nutr 1994; 59:1166S–1170S.Google Scholar
  48. 48.
    Zhang Y, Talalay P. Anticarcinogenic activities of organic isothiocyanates: chemistry and mechanisms. Cancer Research 1994; 54:1976s-1981 s.Google Scholar
  49. 49.
    Wattenberg LW. Inhibition of neoplasia by minor dietary constituents. Cancer Res 1983; 43:2448s-2453s.Google Scholar
  50. 50.
    Sugie S, Okumura A, Tanaka T, Mori H. Inhibitory effects of benzyl isothiocyanate and benzyl thiocyanate on diethylnitrosamine-induced hepatocarcinogenesis in rats. Jpn J Cancer Res 1993; 84: 865–870.Google Scholar
  51. 51.
    Daehnfeldt JL. Cytostatic activity and metabolic effects of aromatic isothiocyanic acid esters. Biochem Pharrn 1968; 17:511–518.Google Scholar
  52. 52.
    Loub WD, Wattenberg LW, Davis DW. Aryl hydrocarbon hydroxylase induction in rat tissues by naturally occurring indoles of cruciferous plants. J Natl Cancer Inst 1975; 54:985–988.Google Scholar
  53. 53.
    Mehta RG, Liu J, Constantinou A, et al. Cancer chemopreventive activity of brassinin, a phytoalexin from cabbage. Carcinogenesis 1995; 16:399–404.Google Scholar
  54. 54.
    Bjeldanes LF, Kim JY, Grose KR, Bartholomew JC, Bradfield CA. Aromatic hydrocarbon responsiveness-receptor agonists generated from indole-3-carbinol in vitro and in vivo: comparisons with 2,3,7,8-tetrachlorodibenzo-p-dioxin. Proc Natl Acad Sci 1991; 88:9543–9547.Google Scholar
  55. 55.
    Shertzer HG. Indole-3-carbinol protects against covalent binding of benzo[a]pyrene and N-nitrosodimethylamine metabolites to mouse liver macromolecules. Chem-Biol Interactions 1984; 48:81–90.Google Scholar
  56. 56.
    Kojima T, Tanaka T, Mori H. Chemoprevention of spontaneous endometrial cancer in female Donryu rats by dietary indole-3-carbinol. Cancer Res 1994; 54:1446–1449.Google Scholar
  57. 57.
    Tiwari RK, Guo L, Bradlow HL, Telang NT, Osborne MP. Selective responsiveness of human breast cancer cells to indole-3-carbinol, a chemopreventive agent. J Natl Cancer Inst 1994; 86:126–131.Google Scholar
  58. 58.
    Jellinck PH, Michnovicz JJ, Bradlow HL. Influence of indole-3-carbinol on the hepatic microsomal formation of catechol estrogens. Steroids 1991; 56:446–450.Google Scholar
  59. 59.
    Michnovicz JJ, Bradlow HL. Altered estrogen metabolism and excretion in humans following consumption of indole-3-carbinol. Nutr Cancer 1991; 16:59–66.Google Scholar
  60. 60.
    Li Y, Wang E, Patten CJ, Chen L, Yang CS. Effects of flavonoids on cytochrome P450-dependent acetaminophen metabolism in rats and human liver microsomes. Drug Metab Disp 1994; 22:566–571.Google Scholar
  61. 61.
    Kandaswami C, Perkins E, Drzewiecki G, Soloniuk DS, Middleton Jr E. Differential inhibition of proliferation of human squamous cell carcinoma, gliosarcoma and embryonic fibroblast-like lung cells in culture by plant flavonoids. Anti-Cancer Drugs 1992; 3:525–530.Google Scholar
  62. 62.
    Bracke M, Vyncke B, Opdenakker G, Foidart JM, De Pestel G, Mareel M. Effect of catechins and citrus flavonoids on invasion in vitro. Clin Exper Metastasis 1991; 9:13–25.Google Scholar
  63. 63.
    Das M, Mukhtar H, Bik DP, Bickers DR. Inhibition of epidermal xenobiotic metabolism in SENCAR mice by naturally occurring plant phenols. Cancer Res 1987; 47:760–766.Google Scholar
  64. 64.
    Verma AK, Johnson JA, Gould MN, Tanner MA. Inhibition of 7,12-dimethylbenz(a)anthracene- and N-nitrosomethylurea-induced rat mammary cancer by dietary flavonol quercetin. Cancer Res 1988; 48:5754–5758.Google Scholar
  65. 65.
    Mukhtar H, Das M, Khan WA, Wang ZY, Bik DP, Bickers DR. Exceptional activity of tannic acid among naturally occurring plant phenols in protecting against 7,12-dimethylbenz(a)anthracene-, benzo(a)pyrene, 3-methylcholanthrene-, and N-methyl-N-nitrosourea-induced skin tumorigenesis in mice. Cancer Res 1988;48:2361–2365.Google Scholar
  66. 66.
    Nakayama T, Yamada M, Osawa T, Kawakishi S. Suppression of active oxygen-induced cytotoxicity by flavonoids. Biochem Pharm 1993; 45:265–267.Google Scholar
  67. 67.
    Ranelletti FO, Ricci R, Larocca LM, et al. Growth-inhibitory effect of quercetin and presence of type-II estrogen-binding sites in human colon-cancer cell lines and primary colorectal tumors. Init J Cancer 1992; 50:486–492.Google Scholar
  68. 68.
    Graham HN. Green tea composition, consumption, and polyphenol chemistry. Prev Med 1992; 21:334–350.Google Scholar
  69. 69.
    Yang CS, Wang ZY, Hong JY. Inhibition of tumorigenesis by chemicals from garlic and tea. Adv Exp Med Biol 1994; 354:113–122.Google Scholar
  70. 70.
    La Vecchia C, Negri E, Franceschi S, D’Avanzo B, Boyle P. Tea consumption and cancer risk. Nutr Cancer 1992; 17:27–31.Google Scholar
  71. 71.
    Gao YT, McLaughlin JK, Blot WJ, Ji BT, Dai Q, Fraumeni Jr JF Reduced risk of esophageal cancer associated with green tea consumption. J Natl Cancer Inst 1994; 86:855–858.Google Scholar
  72. 72.
    Mukhtar H, Katiyar SK, Agarwal R. Green tea and skin-anticarcinogenic effects. J Invest Derm 1994; 102:3–7.Google Scholar
  73. 73.
    Narisawa T, Fukaura Y. A very low dose of green tea polyphenols in drinking water prevents N-methyl-N-nitrosourea-induced colon carcinogenesis in F344 rats. Jpn J Cancer Res 1993; 84:1007–1009.Google Scholar
  74. 74.
    Nishida H, Omori M, Fukutomi Y, et al. Inhibitory effects of (-)-epigallocatechin gallate on spontaneous hepatoma in C3H/HeNCrj mice and human hepatoma-derived PLC/PRF/5 cells. Jpn J Cancer Res 1994; 85:221–225.Google Scholar
  75. 75.
    Katiyar SK, Agarwal R, Zaim MT, Mukhtar H. Protection against N-nitrosodiethylamine and benzo[a]pyrene-induced forestomach and lung tumorigenesis in A/J mice by green tea. Carcinogenesis 1993; 14:849–855.Google Scholar
  76. 76.
    Komori A, Yatsunami J, Okabe S, et al. Anticarcinogenic activity of green tea polyphenols. Jpn J Clin Oncol 1993; 23:186–190.Google Scholar
  77. 77.
    Yin P, Zhao J, Cheng S, Zhu Q, Liu Z, Zhengguo L. Experimental studies of the inhibitory effects of green tea catechin on mice large intestinal cancers induced by 1,2-dimethylhydrazine. Cancer Lett 1994; 79:33–38.Google Scholar
  78. 78.
    Shi ST, Wang ZY, Smith TJ, et al. Effects of green tea and black tea on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone bioactivation, DNA methylation, and lung tumorigenesis in A/J mice. Cancer Res 1994; 54:4641–4647.Google Scholar
  79. 79.
    Hirose M, Hoshiya T, Akagi K, Futakuchi M, Ito N. Inhibition of mammary gland carcinogenesis by green tea catechins and other naturally occurring antioxidants in female Sprague-Dawley rats pretreated with 7,12-dimethylbenz[alpha]anthracene. Cancer Lett 1994; 83:149–156.Google Scholar
  80. 80.
    Xu Y, Ho CT, Amin SG, Han C, Chung FL. Inhibition of tobacco-specific nitrosamine-induced lung tumorigenesis in A/J mice by green tea and its major polyphenol as antioxidants. Cancer Res 1992; 52:3875–3879.Google Scholar
  81. 81.
    Wu YN, Wang HZ, Li JS, Han C. The inhibitory effect of Chinese tea and its polyphenols on in vitro and in vivo N-nitrosation. Biomed Environ Sci 1993; 6:237–258.Google Scholar
  82. 82.
    Wang ZY, Huang MT, Lou YR, et al. Inhibitory effects of black tea, green tea, decaffeinated black tea, and decaffeinated green tea on ultraviolet B light-induced skin carcinogenesis in 7,12-dimethylbenz[a]anthracene-initiated SKH-1 mice. Cancer Res 1994; 54:3428–3435.Google Scholar
  83. 83.
    Wang ZY, Hong JY, Huang MT, Reuhl KR, Conney AH, Yang CS. Inhibition of N-nitrosodiethylamineand 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced tumorigenesis inA/J mice by green tea and black tea. Cancer Res 1992; 52:1943–1947.Google Scholar
  84. 84.
    Fujita Y, Yamane T, Tanaka M, et al. Inhibitory effect of (-)-epigallocatechin gallate on carcinogenesis with N-ethyl-N’-nitro-N-nitrosoguanidine in mouse duodenum. Jpn J Cancer Res 1989; 80:503–505.Google Scholar
  85. 85.
    Huang MT, Ho CT, Wang ZY, et al. Inhibitory effect of topical application of a green tea polyphenol fraction on tumor initiation and promotion in mouse skin. Carcinogenesis 1992; 13:947–954.Google Scholar
  86. 86.
    Bu-Abbas A, Clifford MN, Ioannides C, Walker R. Stimulation of rat hepatic UDP-glucuronosyl transferase activity following treatment with green tea. Food Chem Toxicol 1995; 33:27–30.Google Scholar
  87. 87.
    Sohn OS, Surace A, Fiala ES, et al. Effects of green and black tea on hepatic xenobiotic metabolizing systems in the male F344 rat. Xenobiotica 1994; 24:119–127.Google Scholar
  88. 88.
    Khan SG, Katiyar SK, Agarwal R, Mukhtar H. Enhancement of antioxidant and phase II enzymes by oral feeding of green tea polyphenols in drinking water to SKH-1 hairless mice: possible role in cancer chemoprevention. Cancer Res 1992; 52:4050–4052.Google Scholar
  89. 89.
    Katiyar SK, Agarwal R, Mukhtar H. Inhibition of both stage I and stage II skin tumor promotion in SEN-CAR mice by a polyphenolic fraction isolated from green tea: inhibition depends on the duration of polyphenol treatment. Carcinogenesis 1993; 14:2641–2643.Google Scholar
  90. 90.
    Guengerich FP Kim DH. In vitro inhibition of dihydropyridine oxidation and aflatoxin B 1 activation in human liver microsomes by naringenin and other flavonoids. Carcinogenesis 1990; 11:2275–2279.Google Scholar
  91. 91.
    Trela BA, Carlson GP. Effect of flavanone on mixed-function oxidase and conjugation reactions in rats. Xenobiotica 1987; 17:11–16.Google Scholar
  92. 92.
    Wei H, Bowen R, Cai Q, Barnes S, Wang Y. Antioxidant and antipromotional effects of the soybean isoflavone genistein. Proc Soc Exp Biol Med 1995; 208:124–130.Google Scholar
  93. 93.
    Molteni A, Brizio-Molteni L, Persky V. In vitro hormonal effects of soybean isoflavones. J Nutr 1995; 125:751S–756S.Google Scholar
  94. 94.
    Herman C, Adlercreutz T, Goldin BR, et al. Soybean phytoestrogen intake and cancer risk. J Nutr 1995; 125:757S–770S.Google Scholar
  95. 95.
    Lamartiniere CA, Moore J, Holland M, Barnes S. Neonatal genistein chemoprevents mammary cancer. Proc Soc Exp Biol Med 1995: 208:120–123.Google Scholar
  96. 96.
    Fotsis T, Pepper M, Adlercreutz H, et al. Genistein, a dietary-derived inhibitor of in vitro angiogenesis. Proc Natl Acad Sci USA 1993; 90:2690–2694.Google Scholar
  97. 97.
    Shugart L, Kao J. Effect of ellagic and caffeic acids on covalent binding of benzo(a)pyrene to epidermal DNA of mouse skin in organ culture. Int J Biochem 1984; 16:571–573.Google Scholar
  98. 98.
    Chang RL, Huang M-T, Wood AW, et al. Effect of ellagic acid and hydroxylated flavonoids on the tumorigenicity of benzo(a)pyrene on mouse skin and in the newborn mouse. Carcinogenesis 1985; 6:1127–1133.Google Scholar
  99. 99.
    Mandal S, Stoner GD. Inhibition of N-nitrosobenzylmethylamine-induced esophageal tumorigenesis in rats by ellagic acid. Carcinogenesis 1990; 11:55–61.Google Scholar
  100. 100.
    Wattenberg LW. Inhibition of carcinogenesis by minor dietary constituents. Cancer Res 1992; 52:2085s-2091 s.Google Scholar
  101. 101.
    Elegbede JA, Maltzman TH, Elson CE, Gould MN. Effects of anticarcinogenic monoterpenes on phase II hepatic drug metabolizing enzymes. Carcinogenesis 1993; 14:1221–1223.Google Scholar
  102. 102.
    Wattenberg LW, Coccia JB. Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone carcinogenesis in mice by D-limonene and citrus fruit oils. Carcinogenesis 1991; 12:115–117.Google Scholar
  103. 103.
    Crowell PL, Gould MN. Chemoprevention and therapy of cancer by d-limonene. Crit Rev Oncogen 1994; 5:1–22.Google Scholar
  104. 104.
    Larsen MC, Brake PB, Parmar D, Jefcoate CR. The induction of five rat hepatic P450 cytochromes by phenobarbital and similarly acting compounds is regulated by a sexually dimorphic, dietary-dependent endocrine factor that is highly strain specific. Arch Biochem Biophys 1994; 315:24–34.Google Scholar
  105. 105.
    Ruch RJ, Sigler K. Growth inhibition of rat liver epithelial tumor cells by monoterpenes does not involve Ras plasma membrane association. Carcinogenesis 1994; 15:787–789.Google Scholar
  106. 106.
    Elson CE, Yu SG. The chemoprevention of cancer by mevalonate-derived constituents of fruits and vegetables. J Nutr 1994; 124:607–614.Google Scholar
  107. 107.
    Elegbede JA, Elson CE, Tanner MA, Qureshi A, Gould MN. Regression of rat primary mammary tumors following d-limonene. J Natl Cancer Inst 1986; 76:323–325.Google Scholar
  108. 108.
    Haag JD, Lindstrom MJ, Gould MN. Limonene-induced regression of mammary carcinomas. Cancer Res 1992; 52:4021–4026.Google Scholar
  109. 109.
    Mills JJ, Chari RS, Boyer IJ, Gould MN, Jirtle RL. Induction of apoptosis in liver tumors by the monoterpene perillyl alcohol. Cancer Res 1995; 55:979–983.Google Scholar
  110. 110.
    Hard GC, Whysner J. Risk assessment of d-limonene: an example of male rat-specific renal tumorigens. Crit Rev Toxicol 1994; 24:231–254.Google Scholar

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© Springer Science+Business Media New York 1997

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  • John A. Milner

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