Effect of 2(3)-tert-butyl-4-hydroxyanisole on benzo[a]pyrene metabolism and DNA-binding of benzo[a]pyrene metabolites in isolated mouse hepatocytes.
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.
D000284:Administration, Oral; D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D001192:Arylsulfatases / Q000378:metabolism; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000378:metabolism*; D002083:Butylated Hydroxyanisole / Q000008:administration & dosage / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D005260:Female; D005966:Glucuronidase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D013997:Time Factors; D014018:Tissue Distribution
D000840:Anisoles; D001580:Benzopyrenes; D002083:Butylated Hydroxyanisole; D001564:Benzo(a)pyrene; D004247:DNA; D001192:Arylsulfatases; D005966:Glucuronidase; D005978:Glutathione