Kinetics of depression and recovery of murine hepatic cytochrome P-450 levels after treatment with the interferon inducer polyriboinosinic-polyribocytidylic acid.
In vivo treatment of randombred Swiss Webster mice with polyriboinosinic-polyribocytidylic acid (poly l X poly C) inhibited the induction of cytochrome P-450's by both 3-methylcholanthrene [(MCA) CAS: 56-49-5] and phenobarbitol [(PB) CAS: 50-06-6]. Concomitant treatments with poly l X poly C and a single dose of MCA inhibited the induction of P-450's for 24 hours and delayed the obtainment of the MCA-induced P-450 levels for approximately 48-72 hours. When cytochrome P-450 levels were induced by four successive daily treatments of MCA or PB and when poly l X poly C was given on only the 1st day, induction of P-450's was completely suppressed for 24 hours and obtainment of the maximal P-450 level was delayed by 72-96 hours. Treatment with poly l X poly C of animals preinduced for P-450's by four successive daily treatments with either PB or MCA decreased the P-450 content to the noninduced basal level within 24 hours. The effect was temporary in the MCA-treated mice since P-450 content recovered to the MCA-preinduced levels within 72 hours. PB-dependent P-450 induction was short lived, and no recovery occurred after poly l X poly C treatment of PB-preinduced mice. Reduced hepatic cytochrome P-450 contents correlated with decreased abilities of liver homogenates to metabolically activate benzo [a]pyrene (CAS: 50-32-8) and N-acetyl-2-aminofluorene (CAS: 53-96-3), as scored in an Ames Salmonella typhimurium revertant assay.
Crowe
D O
DO
Reiners
J J
JJ
Nerland
D E
DE
Sonnenfeld
G
G
D000818:Animals; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D007372:Interferons / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D009153:Mutagens / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology*; D013379:Substrate Specificity
D009153:Mutagens; D008748:Methylcholanthrene; D007372:Interferons; D003577:Cytochrome P-450 Enzyme System; D011070:Poly I-C