Effects of butylated hydroxyanisole on the metabolism of benzo[a]pyrene by mouse liver microsomes.
The metabolites of tritium-labeled benzo[a[pyrene (BP) extracted from liver microsomes prepared by butylated hydroxyanisole (BHA)-fed and control female A/HeJ mice were analyzed by high-pressure liquid chromatography. There was an overall decrease in diol formation as well as an increase in the phenol formation in microsomal incubations from the BHA-fed mice compared to the controls. The dione region, when analyzed together with the BP-4,5-oxide peak, showed an overall decrease with BHA feeding. The BP-4,5-oxide was isolated and identified. It was present in both the BHA-fed and control microsomal incubations but was substantially reduced in the former. BP-9,10-oxide and BP-7,8-oxide were not directly demonstrated. Data based on summation of diols and phenols resulting from the breakdown of these oxides indicated that they were present in reduced amounts in the microsomal incubation from BHA-fed mice. The 3-hydroxybenzo[a]pyrene (3-HOBP) was the major metabolite in both microsomal incubations and was present in a significantly higher percentage in the incubations from the BHA-fed mice when compared to control mice. Thus BHA resulted in two metabolic alterations which could result in its exerting an inhibitory effect on BP-induced carcinogenesis. The first was an increase in 3-HOBP, a metabolite of detoxification, and the second was a decrease in epoxidation, which is an activation process.
D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D001580:Benzopyrenes / Q000032:analysis / Q000378:metabolism*; D002083:Butylated Hydroxyanisole / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D004852:Epoxy Compounds / Q000378:metabolism; D005260:Female; D006900:Hydroxylation; D066298:In Vitro Techniques; D051379:Mice; D008805:Mice, Inbred A; D008862:Microsomes, Liver / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism
D000840:Anisoles; D001580:Benzopyrenes; D004852:Epoxy Compounds; D002083:Butylated Hydroxyanisole; D006899:Mixed Function Oxygenases