Covalent binding of benzo(a)pyrene in perfused rat lung following systemic and intratracheal administration

Covalent binding of benzo(a)pyrene to DNA, RNA, and protein of perfused rat lung after intratracheal administration of the substrate was about 50% of that obtained by direct addition of the substrate into the perfusate. Systemic availability of benzo(a)pyrene by absorption from the intratracheal sites was found to be 25%. During single pass perfusion of rat lung as well as in the combined liver-lung recirculating perfusion system, covalent binding after intratracheal exposure to benzo(a)pyrene was reduced to 50-75%. These experiments point out the relative importance of systemic versus inhalation exposure to benzo(a)pyrene in the development of lesions on the lung macromolecules. The elimination capacity of the perfused lung was found to be relatively high as compared to the liver. At constant benzo(a)pyrene infusion by a single pass medium, clearance values of the 5,6-benzoflavone-induced lung with 7.8 ml/min reach almost half of those of a 5,6-benzoflavone-induced liver (15.9 ml/min). The extraction ratios in lung both during bolus administration in the recirculating system and during constant infusion in the nonrecirculating system are 0.25 and 0.29, respectively, and thus amount to half of those measured in the liver (0.45 and 0.53, respectively). Though the liver is able to exert a protective effect against covalent binding of benzo(a)pyrene in the lung, this protection is not complete, and significant amounts of benzo(a)pyrene are expected to escape metabolic transformation by the liver representing a risk for the lung from the circulatory site in addition to that from the respiratory site.