Differences in pulmonary metabolism of benzo(a)pyrene in inbred mouse strains, using the isolated perfused lung

The metabolism of benzo(a)pyrene (BaP) was studied in isolated perfused and ventilated lungs from two inbred strains of mice. C57BL/6 and DBA/2 mice were treated with beta-naphthoflavone (BNF) or corn oil alone in order to reveal strain differences in inducibility of the microsomal enzymes responsible for BaP oxidation. BaP metabolism was quantified by the rate of appearance of free and conjugated 14C-metabolites released into the perfusion medium, and the production of nonextractable metabolites covalently bound to lung macromolecules. In both strains, lungs from mice pretreated with BNF released BaP metabolites at a rate somewhat greater than vehicle-treated controls, without a distinct change in the profile of metabolites. However, the amount of BaP covalently bound to lung macromolecules was increased by BNF pretreatment in C57BL/6 mice only. Thus, release of BaP metabolites into the perfusion medium was not a predictor of the rate of production of reactive metabolites.