Pulmonary microsomal metabolism of benzo[a]pyrene following exposure of rats to silica.
Because some evidence suggests that there may be an increased incidence 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 silica 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 microsomal metabolism of BaP were measured. When the formation of BaP metabolites in equal amounts of lung microsomal tissue from the 2 treatment groups is compared, 3-OH BaP, BaP 4,5-diol, and BaP 9,10-diol are reduced 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 diols and BaP quinones, potentially toxic metabolites, to the relatively nontoxic 3-OH BaP produced by equal amounts of lung microsomal tissue is increased more than threefold following exposure of rats to silica. Since exposure of rats to silica leads to increased levels of lung microsomal protein, the amounts of BaP metabolites that could be produced by all microsomal tissue in the lungs were calculated. 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 by 1.2- to 2.0-fold, but BaP 7,8-diol and the BaP quinones are increased by 3.5-fold. These results demonstrate that exposure of rats to silica may alter the capacity of the lungs to metabolize benzo[a]pyrene, and the greatest effect seems to be enhanced accumulation of BaP 7,8-diol and the BaP quinones.
Miles
P R
PR
Division of Respiratory Disease Studies, National Institute for Occupational Safety, Morgantown, WV 26505, USA.
Ma
J Y
JY
Bowman
L
L
Miller
M R
MR
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D001579:Benzopyrene Hydroxylase / Q000187:drug effects / Q000378:metabolism; D001711:Biotransformation; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D010636:Phenols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012269:Ribosomal Proteins / Q000032:analysis / Q000187:drug effects; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000633:toxicity*
D010636:Phenols; D012269:Ribosomal Proteins; D001564:Benzo(a)pyrene; D012822:Silicon Dioxide; D001579:Benzopyrene Hydroxylase