Cholestasis as an in vivo model for analysis of the induction of liver microsomal monooxygenases by sodium phenobarbital and 3-methylcholanthrene

Cholestasis was used as a model of sharp decrease in the amounts of substrate-binding and catalytic centres of cytochrome P-450 for sodium phenobarbital and 3-methylcholanthrene. Based on this model, the induction effects of sodium phenobarbital and 3-methylcholanthrene on rat liver microsomal monooxygenases were analyzed. Under conditions excluding the primary binding and metabolism of the inducer by monooxygenases, sodium phenobarbital retains its capacity for induction. By contrast, 3-methylcholanthrene exerted no inducing effects under the same conditions as confirmed by the lack of increase of cytochrome P-448 content. From the data obtained it is suggested that in mechanism of sodium phenobarbital induction of liver microsomal monooxygenases the activation of protein synthesis is affected by the inducer itself. As for 3-methylcholanthrene, it is assumed that the synthesis of specific protein (cytochrome P-448) could be initiated by the microsomal metabolites of this inducer.