Metabolism of 14 C-vinyl chloride in vitro and in vivo

Rat liver microsomes metabolise 14 C-vinyl chloride to intermediates which irreversibly bind to the microsomal protein and to soluble proteins and RNA, when these compounds are added to the incubation. A superoxide (O2) generating system comprised of phenazine methosulfate and NADH also converts 14 C-vinyl chloride to metabolites which irreversibly bind to albumin. These data are consistent with the assumption of chloroethylene oxide being the primary reactive metabolite of vinyl chloride. If rats are exposed to 14 C-vinyl chloride, about half of the radioactive metabolites in the liver microsomal fraction is bound irreversibly to microsomal protein, when assessed immediately after exposure. Large amounts of polar, extractable, metabolites are present in the cytosol fraction. The amount of radioactivity in tissues of the rats, irreversibly bound immediately after exposure, comprises 10 - 40% of the total radioactivity in tissues. This percentage rises up to 70% after 48 hrs. Som radioactivity derived from 14 C-vinyl chloride is also incorporated into DNA and RNA of liver. Whereas the peak of incorporation of 14 C into DNA is already reached immediately after exposure to 14 C-vinyl chloride, specific labelling of RNA increases after exposure until its maximum after 24 hours.