Vitamin A and aflatoxin: effect on liver and colon cancer.
A vitamin A (retinyl acetate)-deficient diet enhanced liver cancer in rats exposed to aflatoxin B1 (AFB1) and also caused a 29% incidence of colon cancer. The following factors were considered in attempts to define conditions under which vitamin-A-deprived rats were more susceptible to colon cancer induced by AFB1: liver morphology, enterohepatic recirculation, level of reduced glutathione (GSH) in liver, and differing capacities for conjugation of aflatoxin to GSH. Enzyme concentrations in liver, in intestinal and colon mucosa, and in intestinal and colon contents suggested that AFB1 may have different metabolites and that there may be differing susceptibilities of colon mucosa to carcinogenesis. Binding studies supported this hypothesis. Previous studies have shown that colon epithelium from vitamin-A-deficient rats binds more AFB1 than colon epithelium from normal, vitamin-A-supplemented animals. In the present study, vitamin A supplementation to the vitamin-A-deficient rats before oral administration of 3H-AFB1 significantly decreased the binding capacity at 12 and 15 hours after dosing with the carcinogen. These results suggest that the effect of vitamin A on the metabolism of the carcinogen, particularly on binding of AFB1 to cellular macromolecules, may be the mechanism by which vitamin A modifies aflatoxin's carcinogenic potential, influenced in part through enzymatic mechanisms.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000494:pharmacology*; D000818:Animals; D001579:Benzopyrene Hydroxylase / Q000032:analysis; D003043:Cocarcinogenesis; D003110:Colonic Neoplasms / Q000139:chemically induced*; D005966:Glucuronidase / Q000032:analysis; D005978:Glutathione / Q000032:analysis; D008113:Liver Neoplasms / Q000139:chemically induced*; D008297:Male; D010090:Oxidoreductases, O-Demethylating / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D014801:Vitamin A / Q000494:pharmacology*
D000348:Aflatoxins; D014801:Vitamin A; D016604:Aflatoxin B1; C026048:4-nitroanisole O-demethylase; D010090:Oxidoreductases, O-Demethylating; D001579:Benzopyrene Hydroxylase; D005966:Glucuronidase; D005978:Glutathione