Dietary carotenoids inhibit aflatoxin B1-induced liver preneoplastic foci and DNA damage in the rat: role of the modulation of aflatoxin B1 metabolism
Abstract
To study the effects of carotenoids on the initiation of liver carcinogenesis by aflatoxin B1 (AFB1), male weanling rats were fed beta-carotene, beta-apo-8'-carotenal, canthaxanthin, astaxanthin or lycopene (300 mg/kg diet), or an excess of vitamin A (21000 RE/kg diet), or were injected i.p. with 3-methylcholanthrene (3-MC) (6 x 20 mg/kg body wt) before and during i.p. treatment with AFB1 (2 x 1 mg/kg body wt). The rats were later submitted to 2-acetylaminofluorene treatment and partial hepatectomy, and placental glutathione S-transferase-positive liver foci were detected and quantified. The in vivo effects of carotenoids or of 3-MC on AFB1-induced liver DNA damage were evaluated using different endpoints: liver DNA single-strand breaks (SSB) induced by AFB1, and in vivo binding of [3H]AFB1 to liver DNA and plasma albumin. Finally, the modulation of AFB1 metabolism by carotenoids or by 3-MC was investigated in vitro by incubating [14C]AFB1 with liver microsomes from rats that had been fed with carotenoids or treated by 3-MC, and the metabolites formed by HPLC were analyzed. In contrast to lycopene or to an excess of vitamin A, both of which had no effect, beta-carotene, beta-apo-8'carotenal, astaxanthin and canthaxanthin, as we...Continue Reading
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