Effect of O2 tension on the bioactivation and metabolism of aliphatic halides by primary rat-hepatocyte cultures.
The covalent binding of CCl4 and CF3CHBrCl to cultured rat hepatocytes was enhanced by anoxic conditions, indicative of enhanced reductive biotransformation. The covalent binding of CHCl3 and CHCl2CH2Cl decreased as the O2 concentration was decreased, indicating a preference for oxidative metabolism. Lower O2 tensions decreased the formation of polar water-soluble metabolites with CHCl3 and CHCl2CH2Cl, while CCl4 and CF3CHBrCl were unaffected. The results indicate that primary cultured hepatocytes can reductively biotransform and bioactivate aliphatic halides under anoxic conditions.
D000818:Animals; D001711:Biotransformation; D002251:Carbon Tetrachloride / Q000378:metabolism*; D002478:Cells, Cultured; D002725:Chloroform / Q000378:metabolism*; D006221:Halothane / Q000378:metabolism*; D006843:Hydrocarbons, Chlorinated / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010100:Oxygen / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014240:Trichloroethanes / Q000378:metabolism*
D006843:Hydrocarbons, Chlorinated; D014240:Trichloroethanes; C024567:1,1,2-trichloroethane; D002725:Chloroform; D002251:Carbon Tetrachloride; D010100:Oxygen; D006221:Halothane