METABOLISM OF [C-14]-LABELED AND [CL-36]-LABELED VINYL-CHLORIDE INVIVO AND INVITRO

Label from [14C]vinyl chloride was covalently bound to protein and nucleic acids in vivo and in vitro in the presence of rat liver microsomal fractions or highly purified cytochrome P-450 and NADPH-cytochrome P-450 reductase preparations. The ratio of bound to total non-volatile metabolites increased in going from the in vivo to the microsomal to the purified system. [36Cl]vinyl chloride was metabolized by microsomes and highly purified systems: no label was bound and most could be accounted for as chloride ion. Phenobarbital pretreatment of rats did not induce total metabolism of vinyl chloride in vivo at either 10 or 250 ppm exposure levels; however, binding to protein and RNA was enhanced at the 10 ppm but not the 250 ppm level. Phenobarbital pretreatment increased thein vitro microsomal conversion of vinyl chloride to both total and bound metabolites. A sizeable fraction of the label of [14C]vinyl chloride metabolized in vivo was recovered in the microsomal fraction of the liver, but sodium dodecyl sulfate polyacrylamide gel electrophoresis of in vitro incubations indicated that the metabolites were distributed among many microsomal proteins and not localized to cytochrome P-450. Evidence was obtained for the metabolism of the suspected vinyl chloride metabolite chloroethylene oxide by microsomal epoxide hydratase. However, the epoxide hydratase inhibitor 3,3,3-trichloropropylene oxide, which blocks the microsomal degradation of chloroethylene oxide, did not enhance the level of vinyl chloride bound to either protein or adenosine. © 1979.