Hepatotoxicity of vinyl chloride and 1,1-dichloroethylene. Role of mixed function oxidase system.
Vinyl chloride, an occupational carcinogen, produces acute liver injury in rats pretreated with phenobarbital or Aroclor 1254. Injury appears related to morphologic changes in the endoplasmic reticulum. The degree of injury, as indicated by elevation of serum enzymes derived from the liver, correlates with the magnitude of induction of cytochrome P-450 and its reduction by NADPH. Hepatic injury following 1,1-dichloroethylene exposure differs strikingly from that caused by vinyl chloride and appears to involve plasma membranes, mitochondria, and chromatin and spares endoplasmic reticulum. Induction of cytochrome P-450 appears to protect against 1,1-dichloroethylene but not vinyl chloride.
D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D002273:Carcinogens; D002462:Cell Membrane / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000494:pharmacology; D004000:Dichloroethylenes / Q000494:pharmacology*; D004721:Endoplasmic Reticulum / Q000187:drug effects; D004790:Enzyme Induction; D005978:Glutathione / Q000378:metabolism; D006581:Hexachlorobenzene / Q000494:pharmacology; D006843:Hydrocarbons, Chlorinated / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008113:Liver Neoplasms / Q000139:chemically induced; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000187:drug effects; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009249:NADP; D010088:Oxidoreductases / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D011285:Pregnenolone Carbonitrile / Q000494:pharmacology; D051381:Rats; D013148:Spironolactone / Q000494:pharmacology; D014752:Vinyl Chloride / Q000494:pharmacology*; D014753:Vinyl Compounds / Q000494:pharmacology*
D001140:Aroclors; D002273:Carcinogens; D004000:Dichloroethylenes; D006843:Hydrocarbons, Chlorinated; D014753:Vinyl Compounds; D011285:Pregnenolone Carbonitrile; D013148:Spironolactone; D006581:Hexachlorobenzene; D009249:NADP; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D005978:Glutathione; D014752:Vinyl Chloride; D010634:Phenobarbital