Rat liver microsomal uptake and irreversible protein binding of [1,2-14C]vinyl bromide.

When rat liver microsomes are incubated in a [¹⁴C]vinyl bromide atmosphere, rapid equilibration of vinyl bromide occurs between the gas and the liquid incubation phases. The presence of NADPH in the incubation further increases the uptake of radioactivity into the incubation mixture which is related to microsomal metabolism of vinyl bromide. Saturation of metabolizing enzymes occurs at a partial pressure of vinyl bromide in the gas phase of 0.1 Torr, which is about one order of magnitude less than previously reported for vinyl chloride. The presence of 1,2,3-benzothiadiazole derivatives and SKF 525 A inhibits microsomal metabolism of vinyl bromide. Part of the vinyl bromide metabolites bind irreversibly to the microsomal protein. Irreversible binding depends on NADPH, with the V_max amounting to 6.6 pmol bound/mg of microsomal protein/min. The half-maximal binding occurs at a partial pressure of vinyl bromide in the gas phase of 0.022 Torr. If soluble proteins are added to the microsomal incubation, vinyl bromide metabolites also irreversibly bind to those proteins. Strain differences occur in metabolism of vinyl bromide by liver microsomes from Sprague-Dawley and Wistar rats.