Intermediary Metabolism of Benzo[α]pyrene in the Rat 2

The hepatobiliary system is the primary site of metabolism of polycyclic aromatic hydrocarbons. After administration of C14-benzo[a]pyrene and analysis of bile for metabolites, the metabolic products fell into two main categories—primary and secondary oxidation products. The most significant of the former were 3-hydroxybenzo[a]-pyrene and 6-hydroxybenzo[a]pyrene, and in the secondary oxidation products, 1,6-dihydroxybenzo[a]pyrene and 3,6-dihydroxybenzo[a]pyrene. These metabolites were detectable in several different forms, and under physiologic circumstances underwent either glucuronide or sulfate conjugation. 3-Hydroxybenzo[a]pyrene, though a primary oxidation product, appeared subsequent to several dihydroxy derivatives of 6-hydroxybenzo[a]pyrene. Identification of the F1, X2, and F2 metabolites was partially accomplished, and our findings differed slightly from those published earlier. A labile metabolite could be reconverted to parent benzo[a]pyrene after mild acid treatment. The vehicle used for administration of benzo[a]pyrene significantly modified absorption through the tracheobronchial epithelium. Analysis for radioactivity, paper chromatography, and ultraviolet absorption and fluorescence spectroscopy were used for identification of metabolites. When possible, metabolites in chemically pure form were injected intravenously to establish sequence and site of oxidation.