Abstract

Benzo[ a]pyrene (BP) metabolism and the conjugation and DNA-binding of BP metabolites, was studied using isolated hepatocytes from mice maintained on a diet containing 2(3)- tert-butyl-4-hydroxyanisole (BHA) (7.5 g/kg food) to discover the mechanisms involved in the anticarcinogenic effects of this antioxidant. The antioxidant feeding produced: (a) profound differences in the BP metabolite pattern, (b) no increase in the levels of either the glucuronic acid, the sulfate or the glutathione conjugates and (c) a marked decrease in the level of BP metabolites bound to intracellular DNA. Therefore, the inhibition of DNA-binding observed after administration of BHA, may be due to the change in BP metabolism rather than to an increase in the conjugation of reactive metabolites.

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