Phenobarbital and dexamethasone induce expression of cytochrome P-450 genes from subfamilies IIB, IIC, and IIIA in mouse liver.
Phenobarbital (PB) and dexamethasone (DEX) induce several liver-specific cytochrome P-450 mRNAs in rats. We examined the induction of P-450 mRNAs from families IIB, IIC, and IIIA by PB and DEX in six inbred mouse strains. P-450IIB1-related mRNA species were induced 3- to 13-fold by PB and 3- to 15-fold by DEX in all animals. P-450IIC6-related mRNA species were induced 3- to 7-fold by PB in males and females, and up to 5-fold by DEX in most males but not in female mice, in which DEX was inactive. P-450IIIA-related mRNA species were induced 2- to 7-fold by PB and 2- to 20-fold by DEX in all animals of either sex. In DBA/2J female mice, both inducers triggered a comparable early response (4 hr) at a low dose (10 mg/kg) for all three gene subfamilies, the maximum being reached between 8 and 18 hr of treatment with 100 mg/kg. Under the optimal induction conditions, coadministration of PB and DEX did not lead to any further increase in the responses. These results demonstrate the existence of analogies, as well as striking differences in the inductive effects of PB and DEX between rats and mice. They also indicate the possible involvement of these inducers in related inductive pathways for three cytochrome P-450 gene subfamilies in mouse liver.
McArdle Laboratory for Cancer Research, University of Wisconsin.
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D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics*; D010634:Phenobarbital / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D012333:RNA, Messenger; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D010634:Phenobarbital