Induction of cytochrome P-450 b, e-type isozymes by polychlorionated biphenyls in rat liver

We have studied the induction of cytochrome P-450 b, e-type antigen and mRNA by phenobarbital, 4,4′-dichlorobiphenyl and 2,4,5,2′,4′,5′-hexachlorobiphenyl in male Wistar rat liver. Chronic treatment of rats with 4,4′-dichlorobiphenyl leads to a relatively slow, 20-fold increase in the cytochrome P-450 b,e-type antigen level and to an equivalent increase in the concentration of the corresponding mRNA. Treatment of rats with phenobarbital or 2,4,5,2′,4′,5′-hexachlorobiphenyl results in a faster and more pronounced increase of cytochrome P-450 b,e-type antigen and mRNA levels. Analysis of clones from cDNA banks showed that two types of sequences are induced by phenobarbital corresponding to cytochrome P-450 b and cytochrome P-450 e respectively. 2,4,5,2′,4′,5′-Hexachlorobiphenyl appears to induce primarily a cytochrome P-450b-type sequence. The implications of these results for the study of the mechanism of induction are discussed.