The in vitro oxidative metabolism of benzo(a)pyrene in human liver measured by different assays.

The specific metabolism of benzo(a)pyrene (BP) in adult human liver samples was studied by using triated BP and thin-layer chromatographic separation of metabolites and by using the conventional fluorometric assay. The incubation in vitro of BP with human liver homogenates yielded the usual pattern of metabolites, including several dihydrodiols, phenols and quinones, as well as products bound convalently to protein. Interindividual variation in the production of different metabolites were very large, several ten-fold. The over-all metabolism was inhibited by aminopyrine and SKF 525A but not by 7,8-benzoflavone. The formation of dihydrodiols was inhibited by several epoxide hydratase inhibitors with consequent accumulation of phenols and an unidentified metabolite (possibly BP 4,5-oxide). Radiometric measurement of phenols, total dihydrodiols and individual dihydrodiols correlated well with the fluorometric assay of BP hydroxylase activity.