Induction of benzpyrene hydroxylase by flavone and its derivatives in fetal rat liver explants

Abstract

Fetal rat liver organ culture affords a system for the comparison of the mechanism(s) of induction ∗ of benzpyrene (BP) hydroxylase by flavones and 3-methyl-cholanthrene(3-MC). Flavone and β-naphthoflavone (BNF) were equally potent inducers at 10 −5 M. 4′-halogenated flavone derivatives proved even more effective in this regard; flavanone and the naturally occuring flavone, tangeretin, were inactive. Although BP hydroxylase activity was inhibited by BNF, 3-MC or 4′-bromoflavone when added to homogenates of fetal rat liver explants, no interference by the inducer was observed under the experimental conditions employed in this study. When equal amounts of the induced and control enzyme were mixed, no less than additive enzyme activity was observed. Flavone derivatives and 3-MC appear to act by a similar mechanism in elevating BP hydroxylase, since combinations of inducers at unsaturating levels resulted in an additive effect, while at saturating levels, enzyme induction was no greater than that of the most potent agent alone.