Influence of Hematin, Carbon Tetrachloride and SKF 525-A Administration on the Enhancement of Microsomal Monooxygenase and UDPglucuronosyltransferase by 3,4-Benzpyrene in Rat Liver

Both drug oxidation (cytochrome P-450, and the overall hydroxylation reactions aryl hydrocarbon hydroxylase and p-nitroanisole O-demethylase) and glucuronidation (UDPglucuronosyltransferase both with p-nitrophenol and 4-methylumbelliferone as aglycones) were enhanced by administering a single intraperitoneal dose of 3,4-benzpyrene to rats. The flavoprotein component in the microsomal monooxygenase system, NADPH cytochrome c reductase, was not influenced by 3,4-benzpyrene administration. The intragastric administration of carbon tetrachloride (1 ml/kg body weight) almost totally blocked the microsomal drug oxidation and also suppressed the enhancement of both mixed function oxidase and UDPglucuronosyltransferase by 3,4-benzpyrene. The inhibitor of heme synthesis, hematin, and inhibitor of cytochrome P-450 dependent metabolism, SKF 525-A, also suppressed the enhancement of both microsomal mixed function oxidase and UDPglucuronosyltransferase achieved by 3,4-benzpyrene administration.