Alteration of aflatoxin B1 metabolic profiles and reduction of aflatoxin B1 mutagenicity by hepatic microsomes of rats fed butylated hydroxyanisole.

Effect of administering butylated hydroxyanisole (BHA) on the metabolism of aflatoxin B1 (AFB1) and production of mutagenic metabolites have been compared with those of phenobarbital (PB) and 3-methylcholanthrene (MC) administration in rat liver microsomes. Male Sprague-Dawley rats were treated with these inducers and liver microsomes were isolated. These microsomes were used to metabolize AFB1 and to produce mutagenic metabolites. Results showed that normal rat liver were able to metabolize AFB1 quite actively and produced large amounts of AFB-8,9-epoxide (appearing as the AFB-8,9-dihydrodiol-Tris complex). Upon incubations of normal rat liver microsomes with increasing concentrations of AFB1, a steep dose-related increases of mutagenicity was observed in the Ames test. The PB-microsomes had an increased ability to metabolize AFB1 and particularly the rate for the production of the weakly mutagenic AFQ1 metabolite was markedly increased. Conversely, PB-microsomes had a moderate decrease in its ability to form the strongly mutagenic of AFB-8,9-epoxide metabolite. However, the ability of PB-microsomes to form mutagenic metabolites from AFB1 was somewhat greater than that of the control-microsomes. The MC-microsomes had an increased ability to metabolize AFB1 also. However, instead of the weakly mutagenic AFQ1 metabolite seen with the PB-microsomes, large amounts of the strongly mutagenic AFM1 metabolite was formed. Although AFM1 is not known to be a direct mutagen, it was highly mutagenic upon activation with microsomes. The very steep dose-related increases of mutagenicity and appearance of bacterial toxicity at relatively lower doses of AFB1 may have been caused by the secondary metabolic activation. The ability of BHA-microsomes to metabolize AFB1 was decreased. Among the metabolites produced by the BHA-microsomes, the non-mutagenic AFB2a was formed in significantly increased amounts but the toxic AFB-8,9-epoxide was produced only in much reduced amounts. The AFB2a was not mutagenic even after metabolic activation with microsomes. When increasing concentrations of AFB1 was incubated with BHA-microsomes, a very mild dose-related increases of mutagenicity was observed and the occurence of toxic effects on bacterial growth appeared only at high doses of AFB1. This may have been due both to the reduced rate of overall AFB1 metabolism and to the decreased formation of the highly mutagenic AFB-8,9-epoxide but an increased formation of the non-mutagenic AFB2a metabolite by the BHA-microsomes.(ABSTRACT TRUNCATED AT 400 WORDS)