ROLE OF HEME SYNTHESIS DURING INDUCTION OF HEPATIC MICROSOMAL CYTOCHROME P-450 AND DRUG METABOLISM PRODUCED BY BENZPYRENE

δ-Aminolevulinic acid synthetase, the initial and rate limiting step in hepatic heme synthesis, is induced by both benzpyrene and phenobarbital. Induction of this enzyme by benzpyrene results in the stimulation of glycine-2-14C incorporation into hepatic microsomal heme in vivo and in the induction of cytochrome P-450 and N-demethylase activity. 3-Amino-1,2,4-triazole, an inhibitor of the second step in hepatic heme synthesis, prevents the stimulation of hepatic heme synthesis and the induction of P-450 and N-demethylase activity. It is suggested that induction of δ-aminolevulinic acid synthetase leading to increases in hepatic heme synthesis may be the mechanism by which benzpyrene induces cytochrome P-450 and certain hepatic microsomal oxidations. © 1969.