Vinyl chloride-induced deactivation of cytochrome P-450 and other components of the liver mixed function oxidase system: an in vivo study.
Liver microsomal enzyme activities were measured 24 hr after a 6 hr exposure to 5% vinyl chloride in male rats pretreated with phenobarbital, Aroclor 1254 or the control vehicle. Liver injury as indicated by serum transaminase elevations after vinyl chloride, was found only in phenobarbital and Aroclor 1254 animals while cytochrome P-450 contents and oxidative N-demethylation of aminoantipyrine and ethylmorphine were markedly decreased in all groups. Glucose-6-phosphatase, cytochrome b5 and NADPH and NADH cytochrome P-450 reductase were scarcely affected. This selective enzymatic deactivation is consistent with a cytochrome P-450 centered activation of vinyl chloride to a reactive electrophile.
D000410:Alanine Transaminase / Q000097:blood; D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005037:Ethylmorphine-N-Demethylase / Q000378:metabolism; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D014752:Vinyl Chloride / Q000494:pharmacology*; D014753:Vinyl Compounds / Q000494:pharmacology*; D015049:Zoxazolamine
D001140:Aroclors; D014753:Vinyl Compounds; D003577:Cytochrome P-450 Enzyme System; D015049:Zoxazolamine; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D000633:Aminopyrine N-Demethylase; D005037:Ethylmorphine-N-Demethylase; D009251:NADPH-Ferrihemoprotein Reductase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005952:Glucose-6-Phosphatase; D005978:Glutathione; D014752:Vinyl Chloride; D010634:Phenobarbital