Investigation of the type of induction of microsomal monooxygenases by polycyclic hydrocarbons

The severity of the induced effect of the polycyclic hydrocarbon 3-methylcholanthrene on monooxygenase of the microsomal fraction of the liver as a function of the number of binding sites for this inducer in the active site of cytochrome P-450 was investigated. In vivo models, in which the primary bounding and metabolism of a polycyclic hydrocarbon in the microsomes is increased or sharply inhibited, are presented. It is concluded that in the mechanism of induction by 3-methylcholanthrene, the activation of synthesis of specific protein (cytochrome P-448) is accomplished not by the initial molecule of the inducer, but by products of its primary metabolism in the microsomes.