Characteristics of Benzo(a)pyrene Metabolism by Kidney, Liver, and Lung Microsomal Fractions from Rodents and Humans

The time course of metabolism of benzo(a)pyrene by liver microsomes from rats given injections of corn oil, phenobarbital, or 3-methylcholanthrene was followed by high-pressure liquid chromatography. This method showed nonlinear time courses of benzo(a)pyrene metabolism after 2 min of reaction at low protein concentrations. The formation of all of the benzo(a)pyrene metabolites measured by high-pressure liquid chromatography was not linear with time but was inducible upon pretreatment of rats with either phenobarbital or 3-methylcholanthrene. The benzo(a)-pyrene metabolism activity of hamster liver was not inducible by pretreatment with 3-methylcholanthrene. Hamster and rat lung microsomal fractions metabolized benzo(a)pyrene at 0.5% of the rate of liver microsomal fractions, and the rate of formation of metabolites was increased only by animal pretreatment with 3-methylcholanthrene. The time course of metabolism by hamster and rat lung microsomes was linear up to 15 min. The metabolism of benzo(a)pyrene by microsomal fractions from kidney, liver, and lung of a number of human subjects was studied; the reaction conditions required to limit metabolism to mainly the primary metabolites were established. The microsomal fractions from human kidney and lung were stable to freezing and had metabolic activities which were 40 to 60% as large as those obtained with rodent lung. In addition, lung samples obtained either at resection or autopsy metabolized benzo(a)pyrene at rates which were not statistically different. The activity of human liver microsomes was 15 to 20% of that obtained with rodents. Subjects who had ingested large doses of barbiturates before death had significantly higher levels of benzo(a)pyrene metabolism activity; no correlation between liver or lung monooxygenase activity and smoking habits was readily discernible from the metabolic data. An analysis of the product distribution of the benzo-ring metabolites showed that the human liver and kidney had product ratios which were qualitatively similar to those obtained with rodent tissue. In addition, higher proportions of quinones were formed at the expense of the phenols which cochromatograph with 3-hydroxybenzo(a)pyrene. However, the human lung microsomal fractions catalyzed the formation of a significantly higher proportion of benzo-ring metabolites than did the other human or rodent organs, with the possible exception of hamster lung.