Clearance of benzo(a)pyrene by isolated rat liver and lung: alterations in perfusion and metabolic capacity.

The ability of isolated rat livers and lungs to clear circulating benzo(a)pyrene was examined under conditions of altered perfusion and pretreatment with 3-methylcholanthrene (3-MC). In isolated organs from control rats, pulmonary benzo(a)pyrene clearance was low (approximately 1 ml/min) and independent of flow between 10 and 45 ml/min, whereas hepatic clearance was greater and flow dependent, increasing from 3.2 +/- 0.2 ml/min at a flow of 7 ml/min to 13.2 +/- 0.7 ml/min at a flow of 20 ml/min. 3-MC pretreatment increased markedly the arylhydrocarbon hydroxylase activity of broken cell preparations from both organs. However, clearance of benzo(a)pyrene was not increased in isolated livers by 3-MC pretreatment. On the other hand, clearance did increase and became flow dependent in isolated lungs of 3-MC-pretreated rats. In fact, when organs from these animals were perfused at flows occurring in vivo, hepatic and pulmonary clearance were about equal. These results indicate that flow and metabolic capacity are important determinants of both hepatic and pulmonary clearance of xenobiotic compounds and suggest that alterations in either factor may affect the relative roles of these organs in the total body disposition of xenobiotic compounds.