Modulation of genotoxic and related effects by carotenoids and vitamin A in experimental models: Mechanistic issues

Mutagenesis

Volumn 14, Issue 2, 1999, Pages 153-172

  De Flora, Silvio ^a   Bagnasco, Maria ^a   Vainio, Harri ^b  

^a UNIVERSITY OF GENOA   (Italy)

^b INTERNATIONAL AGENCY FOR RESEARCH ON CANCER   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA CAROTENE; BETA CAROTENE; CAROTENOID; CONNEXIN 43; ENZYME; OXYGEN; RETINAL; RETINOIC ACID; RETINOL; RETINOL ESTER; XENOBIOTIC AGENT;

ANIMAL CELL; ARTICLE; BACTERIUM; CANCER; CELL COMMUNICATION; DATA BASE; DNA DAMAGE; DNA REPAIR; DRUG ACTIVITY; EXPERIMENTAL MODEL; GENE EXPRESSION; GENOTOXICITY; HAMSTER; HIGH RISK PATIENT; HUMAN; LUNG CANCER; METABOLIC ACTIVATION; MOUSE; NONHUMAN; ONCOGENE MYC; PATHOGENESIS; PRIORITY JOURNAL; RAT; SIGNAL TRANSDUCTION; TUMOR PROMOTION;

ANIMALIA; BACTERIA (MICROORGANISMS); CRICETINAE; MAMMALIA; NICOTIANA TABACUM;

EID: 0033050127     PISSN: 02678357     EISSN: None     Source Type: Journal    
DOI: 10.1093/mutage/14.2.153     Document Type: Article

References (140)

1. Abraham, S. K., Sarma, L. and Kevasan, P.C. (1993) Protective effects of chlorogenic acid, curcumin and β-carotene against γ-radiation-induced in vivo chromosomal damage. Mutat. Res., 303, 109-112.
2. Aidoo, A., Lyn-Cook, L.E., Lensing, S., Bishop, M.E. and Warmer, W. (1995) In vivo antimutagenic activity of beta-carotene in rat spleen lymphocytes. Carcinogenesis, 16, 2237-2241.
3. Alaoui-Jamali, M.A., Bélanger, P.M., Rossignol, G. and Castonguay, A. (1991a) Metabolism, sister chromatid exchanges and DNA single-strand breaks induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and their modulation by vitamin A in vitro. Cancer Res., 51, 3946-3950.
4. Alaoui-Jamali, M.A., Rossignol, G. and Castonguay, A. (1991b) Protective effects of vitamin A against the genotoxicity of NNK, a nicotine-derived N-nitrosamine. Carcinogenesis, 12, 379-384.
5. Althaus, F.R., Lawrence, S.D., Sattler, G.L., Longfellow, D.G. and Pitot, H.C. (1982) Chemical quantification of unscheduled DNA synthesis in cultured hepatocytes as an assay for the rapid screening of potential chemical carcinogens. Cancer Res., 42, 3010-3015.
6. Alzieu, P., Cassand P., Colin, C., Grolier P. and Narbonne J.F. (1987) Effect of vitamins A, C and glutathione on the mutagenicity of benzo[a]pyrene mediated by S9 from vitamin A-deficient rats. Mutat. Res., 192, 227-231.
7. Amagase, H., Schaffer, E.M. and Milner, J.A. (1996) Dietary components modify the ability of garlic to suppress 7,12-dimethylbenz[a]anthracene-induced mammary DNA adducts. J. Nutr., 126, 817-824.
8. Arroyo, P.L., Hatch-Pigott, V., Mower, H.F. and Cooney, R.V. (1992) Mutagenicity of nitric oxide and its inhibition by antioxidants. Mutat. Res., 281, 193-202.
9. Azuine, M.A., Goswami, U.C., Kayal, J.J. and Bhide, S.V. (1992) Antimutagenic and anticarcinogenic effects of carotenoids and dietary palm oil. Nutr. Cancer, 17, 287-295.
10. Baird, M.B. and Birnbaum, L.S. (1979) Inhibition of 2-fluorenamine-induced mutagenesis in Salmonella typhimurium by vitamin A. J. Natl Cancer Inst., 63, 1093-1096.
11. Balansky, R., Mircheva, Z. and Blagoeva P. (1994) Modulation of the mutagenic activity of cigarette smoke, cigarette smoke condensate and benzo[a]pyrene in vitro and in vivo. Mutagenesis, 9, 107-112.
12. Balbinder, E., Stick, S.M. and Sharma, O.K. (1983) Complex effects of retinol on the metabolic activation of 2-aminofluorene. Environ. Mutagen., 5, 665-678.
13. Banoub, R.W., Fernstrom, M. and Ruch, R.J. (1996) Lack of growth inhibition or enhancement of gap junctional intercellular communication and connexin 43 expression by β-carotene in murine lung epithelial cells in vitro. Cancer Lett., 108, 35-40.
14. Bayless, J.H., Jablonski, J.E., Roach, S.M. and Sullivan, P.D. (1986) Inhibition of the mutagenicity and metabolism of 6-methyl-benzo[a]pyrene and 6-hydroxymethyl-benzo[a]pyrene. Biochem. Pharmacol., 35, 2313-2322.
15. Belisario, M.A., Pecce, R., Battista, C., Panza, N. and Pacilio, G. (1985) Inhibition of cyclophosphamide mutagenicity by β-carotene. Biomed. Pharmacother., 39, 445-448.
16. Bertram, J.S. and Bortkiewicz, H. (1995) Dietary carotenoids inhibit neoplastic transformation and modulate gene expression in mouse and human cells. Am. J. Clin. Nutr., 62, 1327S-1336S.
17. Bertram, J.S., Pung, A., Churley, M., Kappock, T.J., Wilkins, L.R. and Cooney, R.V. (1991) Diverse carotenoids protect against chemically induced neoplastic transformation. Carcinogenesis, 12, 671-678.
18. Bhattacharya, R.K., Francis, A.R. and Shetty, T.K. (1987) Modifying role of dietary factors on the mutagenicity of aflatoxin B1: in vitro effect of vitamins. Mutat. Res., 188, 121-128.
19. Blaner, W.S. and Olson, J.A. (1994) Retinol and retinoic acid metabolism. In Sporn, M.B., Roberts, A.B. and Goodman, D.S. (eds), The Retinoids: Biology, Chemistry and Medicine, 2nd Edn.Raven Press, New York, NY, pp. 229-255.
20. Bolognesi, C., Ognio, E., Ferreri-Santi, L. and Rossi, L. (1992) Modulation of DNA damage by vitamin A in developing Sprague-Dawley rats. Anticancer Res., 12, 1587-1592.
21. Brockman, H.E., Stack, H.F. and Waters, M.D. (1992) Antimutagenicity profiles of some natural substances. Mutat. Res., 267, 157-172.
22. Budroe, J.D., Shaddock, J.G. and Casciano D.A. (1987) Modulation of ultraviolet light-, ethyl methanesulfonate- and 7,12-dimethyl-benz[a]anthracene-induced unscheduled DNA synthesis by retinol and retinoic acid in the primary rat hepatocyte. Environ. Mol. Mutagen., 10, 129-139.
23. Budroe, J.D., Schol, H.M., Shaddock, J.G. and Casciano, D.A. (1988) Inhibition of 7,12-dimethylbenz[a]anthracene-induced genotoxicity in Chinese hamster ovary cells by retinol and retinoic acid. Carcinogenesis, 9, 1307-1311.
24. 1. Toxicol. Lett., 6, 243-249.
25. Busk, L. and Ahlborg, U.G. (1982a) Retinol (vitamin A) as a modifier of 2-aminofluorene and 2-acetyl-aminofluorene mutagenesis in the Salmonella/microsome assay. Arch. Toxicol., 49, 169-174.
26. Busk, L. and Ahlborg, U.G. (1982b) Retinoids as inhibitors of orthoaminoazotoluene-induced mutagenesis in the Salmonella/liver microsome test. Mutat. Res., 104, 225-231.
27. Busk, L., Ahlborg, U.G. and Albanus, L. (1982) Inhibition of protein pyrolisate mutagenicity by retinol (vitamin A). Fd Chem. Toxicol., 20, 535-539.
28. Busk, L., Sjöström, B. and Ahlborg, U.G. (1984) Effects of vitamin A on cyclophosphamide mutagenicity in vitro (Ames test) and in vivo (mouse micronucleus test). Fd Chem. Toxicol., 22, 725-730.
29. Caliaro, M.J., Vitaux, P., Lafon, C., Lochon, I., Néhmé, A., Valette, A., Canal, P., Bugat, R. and Jozan, S. (1997) Multifactorial mechanism for the potentiation of cisplatin (CDDP) cytotoxicity by all-trans-retinoic acid (ATRA) in human ovarian carcinoma cell lines. Br. J. Cancer, 75, 333-340.
30. Calle, L.M. and Sullivan, P.D. (1982) Screening of antioxidants and other compounds for antimutagenic properties towards benzo[a]pyrene-induced mutagenicity in strain TA98 of Salmonella typhimurium. Mutat. Res., 101, 99-114.
31. Camoirano, A., Balansky, R.M., Bennicelli, C., Izzotti, A., D'Agostini, F. and De Flora, S. (1994) Experimental databases on inhibition of the bacterial mutagenicity of 4-nitroquinoline l-oxide and cigarette smoke. Mutat. Res., 317, 89-109.
32. Cheng, L.L. and Wilkie, D. (1991) Mitochondrial activity and cytotoxicity of vitamin A (retinol) in yeast and human cell cultures. Biochem. Pharmacol., 42, 1237-1240.
33. Colin, C., Narbonne, J.F., Migaud, M.L., Grolier, P., Cassand, P. and Pellissier M.A. (1991) Lipid peroxidation and benzo[a]pyrene activation to mutagenic metabolites: in vivo influence of vitamins A, E and C and glutathione in both dietary vitamin A sufficiency and deficiency. Mutat. Res., 246, 159-168.
34. Cozzi, R., Bona, R., Polani, S. and De Salvia, R. (1990) Retinoids as modulators of metabolism: their inhibitory effect on cyclophosphamide and 7.12-dimethylbenz[a]anthracene induced sister chromatid exchanges in a metabolically competent cell line. Mutagenesis, 5, 397-401.
35. Cozzi, R., Ricordy, R., Aglitti, T., Gatta, V., Perticone, P. and De Salvia, R. (1997) Ascorbic acid and β-carotene as modulators of oxidative damage. Carcinogenesis, 18, 223-228.
36. De Flora, S. (1998) Mechanisms of inhibitors of mutagenesis and carcinogenesis. Mutat. Res., 402, 151-158.
37. De Flora, S. and Ramel, C. (1988) Mechanisms of inhibitors of mutagenesis and carcinogenesis. Classification and overview. Mutat. Res., 202, 285-306.
38. De Flora, S., Bennicelli, C., Camoirano, A., Serra, D. and Hochstein, P. (1988) Influence of DT diaphorase on the mutagenicity of organic and inorganic compounds. Carcinogenesis, 9, 611-617.
39. De Flora, S., Bennicelli, C., Rovida, A., Scatolini, L. and Camoirano, A. (1994) Inhibition of the 'spontaneous' mutagenicity in Salmonella typhimurium TA102 and TA104. Mutat. Res., 307, 157-167.
40. De Flora, S., Balansky, R., Gasparini, L. and Camoirano, A. (1995) Bacterial mutagenicity of cigarette smoke and its interactions with ethanol. Mutagenesis. 10, 47-52.
41. De Flora, S. et al. (1996) DNA adducts in chronic degenerative diseases. Pathogenetic relevance and implications in preventive medicine. Mutat. Res., 366, 197-238.
42. De Flora, S., Izzotti, A., Walsh, D., Degan, P., Petrilli, G.L. and Lewtas, J. (1997) Molecular epidemiology of atherosclerosis. FASEB J., 11, 1021-1031.
43. Decoudu, S., Cassand, P., Daubéze, M., Frayssinet, C. and Narbonne. J.F (1992) Effect of vitamin A dietary intake on in vitro and in vivo activation of aflatoxin B1. Mutat. Res., 269, 269-278.
44. Dozi-Vassiliades, J., Myrtsiotis, A., Granitsas, A. and Mourelatos D. (1985) Induction of sister-chromatid exchanges and cell-cycle delays in human lymphocytes by vitamin A alone or in combination with melphalan and caffeine. Eur. J. Cancer Clin. Oncol., 21, 1089-1092.
45. Einistö, P., Watanabe, M., Ishidate, M., Jr and Nohmi, T. (1991) Mutagenicity of 30 chemicals in Salmonella typhimurium strains possessing different nitroreductase or 0-acetyltransferase activities. Mutat. Res., 259, 95-102.
46. Espinosa-Aguirre, J.J., Reyes, R.E., Rubio, J., Ostrosky-Wegman, P. and Martinez, G. (1993) Mutagenic activity of urban air samples and its modulation by chili extracts. Mutat. Res., 303, 55-61.
47. Ferrari, N., Rocco, M., Aprile, A., Fassina, G. and Vidali, G. (1989) Interaction retinol-chromatin: an analysis of DNA from vitamin A-treated V79 Chinese hamster cells. Biochim. Biophys. Acta, 1007, 30-35.
48. Ferreri, A.M., Grilli, M.P., Capucci, A., Prodi, G., Rocchi, P. and Bianucci, F. (1986) Effect of antioxidants on mutagenesis induced by DMBA in human cells. Nutr. Cancer, 8, 267-272.
49. Gonzales, F.J. and Gelboin, H.V. (1991) Human cytochromes P450: evolution. catalytic activities and interindividual variations in expression. In Gledhill, B.L. and Mauro, F. (eds), New Horizons in Biological Dostmetry. Wiley Liss, New York, NY, pp. 11-20.
50. González de Mejía, E., Loarca-Piña, G. and Ramos-Gõmez, M. (1997a) Antimutagenicity of xanthophylls present in Aztec Marigold (Tagetes erecta) against 1-nitropyrene. Mutat. Res., 389, 219-226.
51. 1 in Salmonella typhimurium. Environ. Mol. Mittagen., 30, 346-353.
52. Gradelet, S., Leclerc., J., Siess, M.H. and Astorg, P.O. (1996) β-Apo-8′-carotenal, but not β-carotene, is a strong inducer of liver citochromes P4501A1 and 1A2 in rat. Xenobiotica, 26, 909-919.
53. 1 carcinogenicity, genotoxicity and metabolism in rat liver by dietary carotenoids: evidence for a protective effect of CYP1A inducers. Cancer Lett., 114, 221-223.
54. Grosse, Y., Chekir-Ghedira, L., Huc, A., Obrecht-Pflumio, S., Dirheimer, G., Bacha, H. and Pfohl-Leszkowicz, A. (1997) Retinol, ascorbic acid and α-tocopherol prevent DNA adduct formation in mice treated with the mycotoxins ochratoxin A and zearalenone. Cancer Lett., 114, 225-229.
55. Han, J.-S. (1992) Effects of various chemical compounds on spontaneous and hydrogen peroxide-induced reversion in strain TA104 of Salmonella typhimurium. Mutat. Res., 266, 77-84.
56. Haveland-Smith, R.B. (1981) Evaluation of genotoxicity of some natural food colors. Mutat. Res., 91, 285-290.
57. Hazuka, M.B., Edwards Prasad, J., Newman, F., Kinzie, J.J. and Prasad, K.N. (1990) Beta-carotene induces morphological differentiation and decreases adenylate cyclase activity in melanoma cells in culture. J. Am. Coll. Nutr., 9, 143-149.
58. He, Y. and Campbell, C. (1990) Effects of carotenoids on aflatoxin B1-induced mutagenesis in S. typhimurium TA100 and TA98. Nutr. Cancer, 13, 243-253.
59. Heywood, R., Palmer, A.K., Gregson, R.L. and Hummler, H. (1985) The toxicity of beta-carotene. Toxicology, 36, 91-100
60. Hossain, M.Z., Wilkens, L.R., Metha, P.P., Lowenstein, W. and Bertram, J.S. (1989) Enhancement of gap junctional communication by retinoids correlates with their ability to inhibit neoplastic transformation. Carcinogenesis, 10, 1743-1748.
61. Huang, C.C. (1987) Retinol (vitamin A) inhibition of dimethylnitrosamine (DMN) and diethylnitrosamine (DEN) induced sister-chromatid exchanges in V79 cells and mutations in Salmonella/microsome assays. Mutat. Res., 187, 133-140.
62. 1 in Chinese hamster V79 cells. Carcinogenesis, 3, 1-5.
63. IARC (1998a) IARC Handbooks of Cancer Prevention, Vol. 2, Carotenoids. International Agency for Research on Cancer, Lyon, France.
64. IARC (1998b) IARC Handbooks of Cancer Prevention, Vol. 3. Vitamin A. International Agency for Research on Cancer, Lyon, France.
65. Ioannides, C., Ayrton, A.D., Keele, A., Lewis, D.F.V., Flatt, P.R. and Walker, R. (1990) Mechanism of the in vitro antimutagenic action of retinol. Mutagenesis, 5, 257-262.
66. Kada, T.K., Tulikawa, K. and Sadaie Y. (1972) In vitro and host-mediated 'rec-assay' procedures for screening chemical mutagens; and phloxine, a mutagenic red dye detected. Mutat. Res., 16, 165-174.
67. Kelloff, G.J., Boone, C.W., Steele, V.E., Crowell, J.A., Lubet, R.A., Greenwald, P., Hawk, E.T., Fay, J.R., Sigman, C.C. (1996) Mechanistic considerations in the evaluation of chemopreventive data. In Stewart, B.W., McGregor, D. and Kleihues, P. (eds), Principles of Chemoprevention. IARC Scientific Publication no. 139. International Agency for Research on Cancer, Lyon, France, pp. 203-219.
68. Knasmüller, S., Huber, W.W., Kienzl, H. and Schulte-Hermann, R. (1992) Inhibition of repairable DNA-damage in Escherichia coli K-12 cells recovered from various organs of nitrosamine-treated mice by vitamin A. phenethylisothiocyanate, oleic acid and triolein. Carcinogenesis, 13, 1643-1650.
69. Krinsky, N.I. (1993a) Micronutrients and their influence on mutagenicity and malignant transformation. Ann. NY Acad. Sci., 686, 229-242.
70. Krinsky, N.I. (1993b) Actions of carotenoids in biological systems. Annu. Rev. Nutr., 13, 561-587.
71. Krinsky, N.I. (1994) Carotenoids and cancer: basic research studies. In Frei.B. (ed.). Natural Antioxidants in Human Health and Disease. Academic Press. New York, NY, pp. 239-261.
72. Kumari, D. and Sinha, P. (1994) Effect of retinol on ochratoxin-produced genotoxicity in mice. Fd Chem. Toxicol., 32, 471-475.
73. Kuroda, Y. (1990) Antimutagenic activity of vitamins in cultured mammalian cells. In Kuroda. Y., Shankel, D.M. and Waters, M.D. (eds), Antimutagenesis and Anticarcinogenesis Mechanisms II. Plenum Publishing. New York, NY, pp. 233-256.
74. Lahiri, M., Maru, G.B. and Bhide, S.V. (1993) Effect of plant phenols, β-carotene and α-tocopherol on benzo[a]pyrene-induced damage in the mouse forestomach mucosa (target organ) and bone marrow polychromatic erythrocytes (non-target organ). Mutat. Res., 303, 97-100.
75. Leo, M.A. and Lieber, C.S. (1985) New pathways for retinol metabolism in liver microsomes. J. Biol. Chem., 260, 5228-5231.
76. Lewis, D.F.V., Ioannides, C. and Parke, D.V. (1986) Molecular dimensions of the substrate binding site of cytochrome P-448. Biochem. Pharmacol., 35, 2179-2185.
77. Manoharan, K. and Banerjee, M.R. (1985) Beta-carotene reduces sister chromatid exchanges induced by chemical carcinogens in mouse mammmary cells in organ culture. Cell. Biol. Int. Rep., 9, 783-789.
78. Marnett, L.J. and Ji, C. (1994) Modulation of oxidant formation in mouse skin in vivo by tumor-promoting phorbol esters. Cancer Res., 54, 1886s-1889s.
79. McCarthy, D.J., Lindamood, C. and Hill, D.L. (1987) Effects of retinoids on metabolizing enzymes and on binding of benzo(a)pyrene to rat tissue DNA. Cancer Res., 47, 5014-5020.
80. Merriman, R.L. and Bertram, J.S. (1979) Reversible inhibition by retinoids of 3-methylcholanthrene-induced neoplastic transformation in CH3/10T1/2 clone cells. Cancer Res., 39, 1661-1666.
81. Mordan, L.J., Bergin, L.M., Budnick, J.E.L., Meegan, R.R. and Bertram, J.S. (1982) Isolation of methylcholanthrene-'initiated' CH3/10T1/2 cells by inhibiting neoplastic progression wilh retinyl acetate. Carcinogenesis, 3, 279-285.
82. Mukherjee, A., Agarwal, K., Aguilar, M.A. and Sharma, A. (1991) Anticlastogenic activity of β-carotene against cyclophosphamide in mice in vivo. Mutat. Res., 263, 41-46.
83. Nikawa,T., Schulz, W.A., van den Brink, C.E., Hanusch, M., van der Saag, P., Stahl, W. and Sies, H. (1995) Efficacy of all-trans-β-carotene, canthaxanthin and all-trans-, 9-cis-and 4-oxoretinoic acids in inducing differentiation of an F9 embryonal carcinoma RARβ-lacZ reporter cell line. Arch. Biochem. Biophys, 316, 665-672.
84. Odin, A.P. (1997) Vitamins as antimutagens: advantages and some possible mechanisms of antimutagenic action. Mutat. Res., 386, 39-67.
85. Okai, Y., Higashi-Okai, K., Nakamura, S.-I., Yano, Y. and Otani, S. (1996) Suppressive effects of retinoids, carotenoids and antioxidant vitamins on heterocyclic amine-induced umu C gene expression in Salmonella typhimurium (TA1535/pSK 1002). Mutat. Res., 368, 133-140.
86. Okuzumi, J., Nishino, H., Murakoshi, M., Iwashima, A., Tanaka, Y., Yamane, T., Fujita, Y. and Takahashi, T. (1990) Inhibitory effects of fucoxanthin, a natural carotenoid, on N-myc expression and cell cycle progression in human malignant tumor cells. Cancer Lett., 55. 75-81.
87. Olson, J.A. (1983) Formation and function of vitamin A. In Porter, J.W. and Spurgeon, D.L. (eds), Biosynthesis of lsoprenoid Compounds. John Wiley & Sons, New York, NY, pp. 371-412.
88. Olson, J.A. (1994) Vitamin A, retinoids and carotenoids. In Shils, M.E., Olson, J.A and Shike, M. (eds), Modern Nutrition in Health and Disease, 8th Edn. Lea & Febiger, Philadelphia, PA, pp. 371-412.
89. Ong, T., Whong, W.-Z., Stewart, J.D. and Brockman, H.E. (1989) Comparative antimutagenicity of 5 compounds against 5 mutagenic complex mixtures in Salmonella typhimurium strain TA98. Mutat. Res., 222, 19-25.
90. Palmer, H.J., Maher, V.M. and McCormick, J.J. (1989) Effect of retinoids on growth factor-induced anchorage independent growth of human fibroblasts. In Vitro Cell. Dev. Biol., 25, 1009-1015.
91. Pfander, H. (1987) Key to Carotenoids, 2nd Edn. Birkhäuser, Basel, Switzerland.
92. Pung, A., Rundhaug, J.E., Yoshizawa, C.N. and Bertram, J.S. (1988) β-Carotene and canthaxanthin inhibit chemically- and physically-induced neoplastic transformation in IOT1/2 cells. Carcinogenesis, 9, 1533-1539.
93. Qin, S. and Huang, C.C. (1985) Effect of retinoids on carcinogen-induced mutagenesis in Salmonella tester strains. Mutat. Res., 142, 115-120.
94. 1, benzo[a]pyrene, or cyclophosphamide. Environ. Mutagen., 8, 839-847.
95. Qin, S., Batt, T. and Huang, C.C. (1985) Influence of retinol on carcinogen-induced sister chromatid exchanges and chromosome aberrations in V79 cells. Environ. Mutagen., 7, 137-146.
96. 1-induced mutagenesis in Salmonella typhimurium TA98 and TA100. Teratogen. Carcinogen. Mutagen., 5, 29-40.
97. Raj, A.S. and Katz, M. (1985) β-Carotene as an inhibitor of benzo(a)pyrene and mytomicin C induced chromosomal breaks in the bone marrow of mice. Can. J. Genet. Cytol., 27, 598-602.
98. Rao, K.P., Ramadevi, G. and Das, U.N. (1986) Vitamin A can prevent genetic damage induced by benzo(a)pyrene to the bone marrow cells of mice. Int. J. Tissue React., 8, 219-223.
99. Renner, H.W. (1985) Anticlastogenic effect of β-carotene in Chinese hamsters. Time and dose response studies with different mutagens Mutat. Res., 144, 251-256.
100. Rocchi, P., Arfellini, G., Capucci, A., Grilli, M.P. and Prodi, G. (1983) Effect of vitamin A palmitale on mutagenesis induced by polycyclic aromatic hydrocarbons in human cells. Carcinogenesis, 4, 245-247.
101. Romert, L., Jansson, T., Curvall, M. and Jenssen, D. (1994) Screening for agents inhibiting the mutagenicity of extracts and constituents of tobacco products. Mutat. Res., 322, 97-110.
102. Rondahl, L., Busk, L., Ahlborg, U.G. and Bergman, K. (1985) Effects of vitamin A on the metabolism and mutagenicity of 2AAF in vitro and on the covalent binding to rat liver DNA/RNA in vivo. Arch. Toxicol., 57, 178-183.
103. Rundhaug, J.E., Pung, A., Read, C.M. and Bertram, J.S. (1988) Uptake and metabolism of β-carotene and retinol by CH310T1/2 cells. Carcinogenesis. 9, 1541-1545.
104. Rutten, A.A.J.J.L., Jongen, W.M.F., de Haan, L.H.J., Hendriksen, E.G.J. and Koeman, J.H. (1988) Effect of retinol and cigarette-smoke condensate on dye-coupled intercellular communication between hamster tracheal epithelial cells. Carcinogenesis, 9, 315-320.
105. Salvadori, D.M.F., Ribeiro, L.R., Oliveira, M.D.M., Pereira, C.A.B. and Becan, W. (1992) The protective effect of β-carotene on genotoxicity induced by cyclophosphamide. Mutat. Res., 265, 237-244.
106. Salvadori, D.M.F., Ribeiro, L.R. and Natarajan, A.T. (1993) The anticlastogenicity of β-carotene evaluated on human hepatoma cells. Mutat. Res., 303, 151-156.
107. Salvadori, D.M.F., Ribeiro, L.R. and Natarajan, A.T. (1994) Effect of β-carotene on clastogenic effects of mitomycin C, methyl methanesulphonate and bleomycin in Chinese hamster ovary cells. Mutagenesis, 9, 53-57.
108. Santamaria, L., Bianchi, A., Arnaboldi, A., Ravetto, C., Bianchi, L., Pizzala, R., Andreoni, L., Santagati, G. and Bermond, P. (1988) Chemoprevention of indirect and direct chemical carcinogenesis by carotenoids as oxygen radical quenchers. Ann. NY Acad. Sci., 534, 584-596.
109. Shetty, T.K., Francis, A.R. and Bhattacharya, R.K. (1988) Modifying role of vitamins on the mutagenic action of N-methyl-N′-nitro-N-nitrosoguanidine. Carcinogenesis, 9, 1513-1515.
110. Sinha, S.P. and Kumari, D. (1994) Vitamin A ameliorates the genotoxicity in mice of aflatoxin B1-containing Aspergillus flavus infested food. Cytobios, 79, 85-95.
111. Sirianni, S.R., Chen, H.H. and Huang, C.C. (1981) Effect of retinoids on plating efficiency, sister-chromatid exchanges (SCE) and mitomycin-C-induced SCE in cultured Chinese hamster cells. Mutat. Res., 90, 175-182.
112. Som, S., Chatterjee, M. and Banerjee, M. (1984) β-Carotene inhibition of 7,12-dimethylbenz[a]anthracene-induced transformation of murine mammary cells in vitro. Carcinogenesis, 5, 937-940.
113. Sporn, M.B. (1984) The Retinoids. Academic Press, New York, NY.
114. Stahl, W., Nicolai, S., Briviba, K., Hanusch, M., Broszeit, G., Peters, M., Martin, H.-D. and Sies, H. (1997) Biological activities of natural and synthetic carotenoids: induction of gap junctional communication and singlet oxygen quenching. Carcinogenesis, 18, 89-92.
115. Stark, A.-A., Pagano, D.A., Glass, G., Kamin-Belsky, N. and Zeiger, R. (1994) The effects of antioxidants and enzymes involved in glutathione metabolism on mutagenesis by glutathione and L-cysteine. Mutat. Res., 308, 215-222.
116. Stich, H.F. and Dunn, B.P. (1986) Relationship between cellular levels of betacarotene and sensitivity to genotoxic agents. Int. J. Cancer, 38, 713-717.
117. Stich, H.F. and Tsang, S.S. (1989) Promoting activity of betel quid ingredients and their inhibition by retinol. Cancer Lett., 45, 71-77.
118. Stich, H.F., Tsang, S.S. and Palcic, B. (1990) The effect of retinoids, carotenoids and phenolics on chromosomal instability of bovine papillomavirus DNA-carrying cells. Mutat. Res., 241, 387-393.
119. Sugimura, T., Okabe, K. and Nagao, M. (1966) The metabolism of 4-nitroquinoline-1-oxide, a carcinogen. III. An enzyme catalyzing the conversion of 4-nitroquinoline-1-oxide to 4-hydroxyaminoquinoline in rat liver and hepatomas. Cancer Res., 26, 1717-1721.
120. Tang, X. and Edenharder, R. (1997) Inhibition of the mutagenicity of 2-nitrofluorene, 3-nitrofluoranthene and l-nitropyrene by vitamins, porphyrins and related compounds and vegetable and fruit juices and solvent extracts. Fd Chem. Toxicol., 35, 373-378.
121. Tavan, E., Maziere, S., Narbonne, J.F. and Cassand, P. (1997) Effects of vitamins A and E on methylazoxymethanol-induced mutagenesis in Salmonella typhimurium strain TA100. Mutat. Res., 377, 231-237.
122. Terwel, L. and van der Hoeven, J.C.M. (1985) Antimutagenic activity of some naturally occurring compounds towards cigarette-smoke condensate and benzo[a]pyrene in the Salmonella/microsome assay. Mutat. Res., 152, 1-4.
123. Umegaki, K., Tacheuchi, N., Ikegami, S. and Ichikawa, T. (1994) Effect of β-carotene on spontaneous and X-ray-induced chromosomal damage in bone marrow cells of mice. Nutr. Cancer, 22, 277-284.
124. Victorin, K., Busk, L. and Ahlborg, U.G. (1987) Retinol (vitamin A) inhibits the mutagenicity of o-aminoazotoluene activated by liver microsomes from several species in the Ames test. Mutat. Res., 179, 41-48.
125. Wang, C.-J., Shiah, H.-S. and Lin, J.-K. (1991a) Modulatory effect of crocetin on aflatoxin B1 cytotoxicity and DNA adduct formation in C3H10T1/2 fibroblast cell. Cancer Lett., 56, 1-10.
126. 1 in rats. Carcinogenesis, 12, 459-462.
127. Wang, W. and Higuchi, C.M. (1995) Induction of NAD(P)H:quinone reductase by vitamins A. E and C in Colo205 colon cancer cells. Cancer Lett., 98, 63-69.
128. Waters, M.D., Brady, A.L., Stack, H.F. and Brockman, H.E. (1990) Antimutagenicity profiles for some model compounds. Mutat. Res., 238, 57-85.
129. Waters, M.D., Stack, H.F., Jackson, M.A. and Brockman, H.E (1996a) Interpretation of short-term test data: implications for assessment of chemopreventive activity. In Stewart, B.W., McGregor, D. and Kleihues, P. (eds). Principles of Chemoprevention. IARC Scientific Publication no. 139, International Agency for Research on Cancer, Lyon, France, pp. 313-332.
130. Waters, M.D., Stack, H.F., Jackson, M.A., Brockman, H.E. and De Flora, S. (1996b) Activity profiles of antimutagens: in vitro and in vivo data. Mutat. Res., 350, 109-129.
131. Wattenberg, L.W. (1981) Inhibitors of chemical carcinogens. In Burchenal, J.H. and Oettgen, H.F. (eds), Cancer. Achievements, Challenges and Prospects for the 1980s. Grune & Stratton, New York, NY. pp. 517-540.
132. Webster, R.P., Gawde, M.D. and Bhattacharya, R.K. (1996) Effect of different vitamin A status on carcinogen-induced DNA damage in repair enzymes in rats. In Vivo, 10, 113-118.
133. Weitberg, A.B., Weitzman, S.A., Clark, E.P. and Slossel, T.P. (1985) Effects of antioxidants on antioxidant-induced sister chromatid exchange formation. J. Clin. Invest., 75, 1835-1841.
134. White, W.E., Jr and Rock, S.G. (1981) Lack of comutagenicity by norharman and other compounds on revertants induced by photolabeling with 2-azido-9-fluorenone oxime. Mutat. Res., 84, 263-271.
135. Whong, W.-Z., Stewart, J., Brockman, H.E. and Ong, T.-M. (1988) Comparative antimutagenicity of chlorophyllin and five other agents against aflatoxin B1-induced reversion in Salmonella typhimurium strain TA98. Teratogen. Carcinogen. Mutagen., 8, 215-224.
136. Wilmer, J.W.G.M. and Spit, B.J. (1986) Influence of retinoids on the mutagenicity of cigarette-smoke condensate in Salmonella typhimurium TA98. Mutat. Res., 173, 9-11.
137. Wolterbeek, A.P.M., Roggeband, R., van Morsel, C.J.A., Baan, R.A., Koeman, J.H., Feron, V.J. and Rutten, A.A.J.J.L. (1995) Vitamin A and β-carotene influence the level of benzo[a]pyrene-induced DNA adducts and DNA-repair activities in hamster tracheal epithelium in organ culture. Cancer Lett., 91, 205-214.
138. Yu, M.-W., Zhang, Y.-J., Blaner, W.-S. and Samella, R.M. (1994) Influence of vitamins A, C and E and β-carotene on aflatoxin B1, binding to DNA in woodchucks hepatocytes. Cancer, 73, 596-604.
139. Zhang, L.-X., Cooney, R.V. and Bertram, J.-S. (1991) Carotenoids enhance gap junctional communication and inhibit lipid peroxidation in C3H/10T1/2 cells: relationship to their cancer chemopreventive action. Carcinogenesis, 12, 2109-2114.
140. Zhang, L.-X., Cooney, R.V. and Bertram, J.-S. (1992) Carotenoids up-regulate connexin 43 gene expression independent of their provitamin A or antioxidant properties. Cancer Res., 52, 5707-5712.