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.
D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D004247:DNA / Q000032:analysis; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction / Q000187:drug effects; D007120:Immunochemistry; D007525:Isoelectric Focusing; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D007527:Isoenzymes; D012333:RNA, Messenger; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; C029861:4,4'-dichlorobiphenyl; D010634:Phenobarbital; C014024:2,4,5,2',4',5'-hexachlorobiphenyl