Dog pulmonary macrophage metabolism of free and particle-associated [14C]benzo[a]pyrene.

Pulmonary macrophages (PM) are involved in the clearance of inhaled particulate matter from the lung. PM also are capable of metabolizing xenobiotics such as benzo[a]pyrene (BaP). The objective of this investigation was to measure the ability of PM isolated from dogs to metabolize BaP coated onto diesel exhaust particles and to compare this metabolism with that of BaP in solution. PM were isolated from male beagle dogs and incubated with 1 microM [14C]BaP (solution or diesel particle coated) for select times up to 48 h. After incubation of PM with [14C]BaP, both the cells and the media were individually analyzed for [14C]BaP metabolites by high-performance liquid chromatography. Total quantities of [14C]BaP metabolites in both the media (125 pmol/10(6) cells) and cells (45 pmol/10(6) cells) increased with incubation time for up to 48 h. BaP-9,10-diol and BaP-7,8-diol were the major metabolites in organic extracts from the culture media, whereas BaP-7,8-diol and BaP-4,5-diol were the major metabolites in extracts of cells. Small quantities of BaP phenols and BaP quinones were detected in both the cells and media. Total quantities of BaP metabolites (20-30 pmol/10(6) cells) were not significantly different when PM were incubated for 24 h with either [14C]BaP in solution or [14C]BaP coated on diesel particles. The data suggest that particles retained in lungs are capable of being acted upon by PM metabolizing enzymes and that the ensuing metabolism may play an important role in the metabolic fate of organic material inhaled on particulate matter.