Kinetic Analysis of the Metabolism of Benzo(a)pyrene to Phenols, Dihydrodiols, and Quinones by High-Pressure Chromatography Compared to Anatysis by Aryl Hydrocarbon Hydroxylase Assay, and the Effect of Enzyme Induction'

BP4 is a prototype carcinogenic polycychic aromatic hydrocarbon and is a ubiquitous environmental pollutant (28) which may cause cancer in humans. BP or its metabo lites are cytotoxic and mutagenic in mammalian cells (19, 20) and bacteria (2) and cause mammalian cell transforma tion and toxicity (3, 4, 13, 19). BP is metabolized to epoxides (15, 36), phenols, dihydrodiols, quinones, and water-soluble conjugates (8, 10, 15, 23, 33, 34). These reactions are catalyzed primarily by the microsomal mixed function oxidases coupled with hydratases and transferases present in most mammalian tissues (7, 11, 14, 26, 27). The microsomal oxidase also catalyze the metabolic activation of BP to active intermediates that are covalently bound to DNA (6, 12, 16). A major requirement for understanding the mechanism of polycychic hydrocarbon carcinogenesis is a detailed knowl edge of the profile of metabohites formed and the factors regulating their formation. Detoxification and activation processes (9, 11— 14) can then be differentiated by the study of the properties and amount of each metabohite formed. The metabolic products of BP formed by microsomes and tissue preparations from a variety of sources have been reported (5, 15, 23, 29, 33—35),and thin-layer and column chromatography have been the major analytical tools in the analyses of BP metabohites. The tedious and inefficient separation of metabohites by these methods have made the