Effect of administering butylated hydroxyanisole (BHA) on the metabolism of aflatoxin B
1 (AFB
1) 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 AFB
1 and to produce mutagenic metabolites. Results showed that normal rat, liver were able to metabolize AFB
1 quite actively and produced large amounts of AFB-8, 9-epoxide (aprearing as the AFB-8, 9-dihydrodiol-Tris complex). Upon incubations of normal rat liver microsomes with increasing concentrations of AFB
1, a steep dose-related increases of mutagenicity was observed in the Ames test. The PB-microsomes had an increased ability to metabolize AFB
1 and particularly the rate for the production of the weakly mutagenic AFQ
1 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 AFB-1 was somewhat greater than that of the control-microsomes. The MC-microsomes had an increased ability to metabolize AFB
1 also. However instead of the weakly mutagenic AFQ
1 metabolite seen with the PB-microsomes, large amounts of the strongly mutagenic AFM
1 metabolite was formed. Although AFM
1 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 AFB
1 may have ken caused by the secondary metabolic activation. The ability of BHA-microsomes to metabolize AFB
1 was decreased. Among the metabolites produced by the BHA-microsomes, the non-mutagenic AFB
<2a> was formed in significantly increased amounts but the toxic AFB-8, 9-epoxide vas produced only in much reduced amounts. The AFB
<2a> was not mutagenic even after metabolic activation with microsomes. When increasing concentrations of AFB
1 was incubated with BHA-microsomes, a very mild dose-related increases of mutagenicity was observed and the occurance of toxic effects on bacterial growth appeared only at high doses of AFB
1. This may have ken due both to the reduced rate of overall AFB
1 metabolism and to the decreased formation of the highly mutagenic AFB-8, 9-epoxide but an increased formation of the non-mutagenic AFB
<2a> metabolite by the BHA-microsomes. Such a reduced rate of formation of the toxic AFB-8, 9-epoxide but an increased production of the non-toxic AFB
<2a> metabolite by the BHA-microsomes may have been, at least partially. responsible for the anticarcinogenic effect of BHA.
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