Metabolism of benzo[a]pyrene by the isolated perfused rabbit lung.

The metabolism of benzo[a]pyrene (BP) was studied in the isolated perfused rabbit lung and in rabbit pulmonary microsomes. Pretreatment of rabbits with 3-methylcholanthrene did not increase the metabolism of BP by microsomal preparations, and the pretreatment did not induce cytochrome P-448 in pulmonary microsomes. In the isolated perfused lung, BP was metabolized at a rate of about 6 nmol/min/g of lung. The intermediate arene oxides formed from BP in the isolated perfused lung were metabolized nonoxidatively by epoxide hydrase and glutathione S-transferases. The rates of the latter reactions were at least an order of magnitude less than the overall rate of metabolism. Pretreatment of the animals with 3-methylcholanthrene increased only the apparent rate of the epoxide hydrase reaction. In the isolated perfused lung, BP and some of its less polar metabolites (i.e., quinones and phenolic derivatives) were preferentially partitioned into lung tissue, precluding accurate measurement of metabolic rates by analysis of the perfusion medium alone. Covalent binding of BP-derived radioactivity to lung tissue occurred, but relatively high variability in this parameter in lungs from 3-methylcholanthrene-pretreated animals did not allow measurement of a significant difference from control lungs.