| Popis: |
Changes in the extent and pattern of benzo(a)pyrene metabolism were investigated in lungs isolated from rats following ozone exposures that are associated with the proliferation of alveolar and bronchiolar epithelia. Radiolabel incorporation into metabolic products were determined at the end of 60 min perfusions with 50-55 nmol of [6-3H] [7, 10-14C] benzo(a)pyrene (BaP), which in unexposed lungs resulted in a total BaP utilization of 0.77 +/- 0.05 nmol [14C] BaP/h/lung, recovered bound to tissue macromolecules (12%), as tissue and perfusate ethyl acetate-soluble products (59%), and as perfusate water-soluble conjugates (29%). Total metabolism at the sixth position of the BaP molecule was indicated by a 3H2O production of 0.07 +/- 0.01 nmol BaP/h per lung, that resulted in the formation of quinones (33%), acid-hydrolysable (40%) and acid-resistant (27%) water-soluble products, indicated by 14C- minus 3H-labelling. Ozone-exposed lungs demonstrated an increased total [14C] BaP utilization to 3.05 +/- 0.05 nmol/h/lung. Although BaP metabolism to all products was increased, the proportion of metabolism involving the 6th position was enhanced from 10% to 25% of total BaP utilization, which was accounted for by relative increases in tissue retained quinones and in perfusate acid-hydrolysable conjugates. These data demonstrated that quinone formation represents a major pathway of lung polycyclic aromatic hydrocarbon metabolism that is greatly enhanced in lungs with proliferating epithelia associated with oxidant exposure. |
