Depressant effects of the interferon inducer polyriboinosinic:polyribocytidylic acid on cytochrome P-450 hemoproteins.
Partially purified fractions of cytochrome P-450 were prepared from hepatic microsomes recovered from male rats 12 h after administration of either saline or polyriboinosinic:polyribocytidylic acid (poly I:C). Poly I:C reduced the microsomal concentration of cytochrome P-450 by 19% and decreased the maximal binding spectrum (delta Amax) resulting from addition of the type-II substrate 2,4-dichloro-6-phenylphenoxyethylamine to one fraction (B2) while increasing the affinity of that fraction for this substrate. Poly I:C also reduced the microsomal hydroxylation of benzo(a)pyrene and the N-demethylation of benzphetamine by the other fraction (B1). Since 14C-leucine incorporation into cytochrome P-450 was increased in poly I:C-treated rats, it is suggested that poly I:C depresses hepatic mixed-function oxidase activity by increasing the rate of degradation of specific cytochrome P-450s.
D000818:Animals; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000378:metabolism; D001589:Benzphetamine / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006900:Hydroxylation; D007930:Leucine / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D001580:Benzopyrenes; D002250:Carbon Radioisotopes; D001589:Benzphetamine; D001564:Benzo(a)pyrene; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D007930:Leucine; D011070:Poly I-C