Dietary carotenoids inhibit aflatoxin B-1-induced liver preneoplastic foci and DNA damage in the rat: Role of the modulation of aflatoxin B-1 metabolism

作者：Gradelet S; Le Bon AM; Berges R; Suschetet M; Astorg P^*

来源：Carcinogenesis, 1998, 19(3): 403-411.

DOI：10.1093/carcin/19.3.403

To study the effects of carotenoids on the initiation of liver carcinogenesis by aflatoxin B-1 (AFB(1)), 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 (21 000 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 AFB(1) (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 AFB(1)-induced liver DNA damage were evaluated using different endpoints: liver DNA single-strand breaks (SSB) induced by AFB(1), and in vivo binding of [H-3]AFB(1) to liver DNA and plasma albumin. Finally, the modulation of AFB(1) metabolism by carotenoids or by 3-MC was investigated in vitro by incubating [C-14]AFB(1) 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 well as 3-MC, were very efficient in reducing the number and the size of liver preneoplastic foci. In a similar way as 3-MC, the P4501A-inducer carotenoids, beta-apo-8'-carotenal astaxanthin and canthaxanthin, decreased in vivo AFB(1)-induced DNA SSB and the binding of AFB(1) to liver DNA and plasma albumin, and increased in vitro AFB(1) metabolism to aflatoxin M-1, a less genotoxic metabolite. It is concluded that these carotenoids exert their protective effect through the deviation of AFB(1) metabolism towards detoxication pathways. In contrast, beta-carotene did not protect hepatic DNA from AFB(1)-induced alterations, and caused only minor changes of AFB(1) metabolism: seemingly, its protective effect against the initiation of liver preneoplastic foci by AFB(1) is mediated by other mechanisms.

• 出版日期1998-3