Induction of cytochrome P-450b,e-type isozymes by polychlorinated biphenyls in rat liver. Molecular cloning of induced mRNAs.

We have studied the induction of cytochrome P-450b,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-450b,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-450b,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-450b and cytochrome P-450e 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.