Combined effects of polychlorinated biphenyls and methylmercury on hepatic microsomal monooxygenases and the hepatotoxic action of bromobenzene.

The combined effects of polychlorinated biphenyls (PCB) and methylmercury were investigated by assaying the activities of hepatic enzymes and by measuring the binding of bromobenzene to microsomal protein. Rats were fed normal or PCB-diet (KC-400-KC-500, 1:1, 50 ppm) for 14 days and methylmercuric chloride (10 mg Hg/kg, s.c.) was given once daily for the last 2 days. The inducing effects of PCB on microsomal cytochrome P-450, cytochrome b5, aminopyrine N-demethylase, aniline hydroxylase, and p-nitroanisole O-demethylase were counteracted by methylmercury. Glucose 6-phosphatase activity was additively decreased by the combination of PCB and methylmercury. The activity of glucose 6-phosphate dehydrogenase in soluble fraction was increased by PCB but reduced by methylmercury. The toxicity of bromobenzene was enhanced by PCB but the effect of PCB was counteracted by methylmercury. The depletion of liver glutathione and the elevation of serum transaminases by bromobenzene were remarkably potentiated by PCB. Methylmercury counteracted the effect of PCB on serum transaminases but not that on liver glutathione. The amount of bromine covalently bound with liver microsomal protein after an injection of bromobenzene and the radioactivity bound with microsomal protein after in vitro incubation of 14C-bromobenzene with microsomes were fortified by PCB pretreatment but depressed by the combining administration of methylmercury.