PULMONARY MICROSOMAL METABOLISM OF BENZO[A]PYRENE FOLLOWING EXPOSURE OF RATS TO SILICA

Because some evidence suggests that there may be an increased incidenc e of lung cancer in silicosis and because previous studies have shown that exposure of rats to silica alters the pulmonary cytochrome P-450 system, we studied the effects of exposing rats to silica on the lung microsomal metabolism of benzo[a]pyrene (BaP). Rats were exposed to si lica by intratracheal administration, lung microsomes were obtained 2 wk later from untreated and silica-treated animals, and the amounts of microsomal tissue and metabolites formed during the in vitro microsom al metabolism of BaP were measured. When the formation of BaP metaboli tes in equal amounts of lung microsomal tissue from the 2 treatment gr oups is compared, 3-OH BaP, BaP 4,5-diol, and BaP 9, 10-diol are reduc ed by 45-70%, but the formation of BaP 7,8-diol or the BaP-quinones is not significantly altered following exposure to silica. In fact, the ratio of the BaP diets and BaP quinones, potentially toxic metabolites , to the relatively nontoxic 3-OH BaP produced by equal amounts of lun g microsomal tissue is increased more than threefold following exposur e of rats to silica. Since exposure of rats to silica leads to increas ed levels of lung microsomal protein, the amounts of BaP metabolites t hat could be produced by all microsomal tissue in the lungs were calcu lated. In silica-treated animals, the calculated total lung production of 3-OH BaP, BaP 4,5-diol, and BaP 9, 10-diol tends to be increased b y 1.2- to 2.0-fold, but BaP 7,8-diol and the BaP quinones are increase d by 3.5-fold. These results demonstrate that exposure of rats to sili ca may alter the capacity of the lungs to metabolize benzo[a]pyrene, a nd the greatest effect seems to be enhanced accumulation of BaP 7,8-di ol and the BaP quinones.