6-1) ALTERATION OF AFLATOXIN B_1 METABOLIC PROFILES AND REDUCTION OF AFLATOXIN B_1 MUTAGENICITY BY HEPATIC MICROSOMES OF RATS FED BUTYLATED HYDROXYANISOLE

概要

論文の詳細を見る
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.
日本トキシコロジー学会の論文
1991-02-28

6-1) ALTERATION OF AFLATOXIN B_1 METABOLIC PROFILES AND REDUCTION OF AFLATOXIN B_1 MUTAGENICITY BY HEPATIC MICROSOMES OF RATS FED BUTYLATED HYDROXYANISOLE

スポンサーリンク

概要

著者

関連論文

スポンサーリンク