Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0037116 (silicosis)
 1,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Because some evidence indicates that there is an increased incidence of lung cancer in silicosis, we studied the effects of exposing rats to silica on the pulmonary microsomal cytochrome P-450 system. Rats were exposed to silica by intratracheal administration, lung microsomes were obtained from untreated and silica-treated animals, and the amount of microsomal tissue, the level of total cytochromes P-450 (all isozymes), the activity of NADPH cytochrome P-450 reductase, the metabolism of two xenobiotics, and the relative amounts of cytochrome P-4502B1 and P-4501A1 were measured. Lungs from silica-treated rats were almost 2-fold heavier and contained more than 10 times more alveolar phospholipids than lungs from untreated animals, indicating that acute silicosis had been produced. In lungs from silica-treated animals, the concentration of microsomal tissue, expressed as milligrams of microsomal protein per gram of lung, was increased by more than 2-fold, and total microsomal protein content was increased by almost 5-fold relative to untreated animals. When expressed as activity or amount per milligram of protein, the microsomal concentrations of NADPH cytochrome P-450 reductase, total cytochromes P-450, 7-ethoxycoumarin (EC)-0-deethylase, and cytochrome P-4502B1 are reduced by approximately 50% in silica-treated rats. However, when expressed as total activity or amount in the lungs, all are increased by approximately 1.5- to 2.5-fold in silica-treated lungs. On the other hand, total lung 7-ethoxyresorufin (ER)-0-deethylase activity and cytochrome P-4501A1 are increased by 4- to 5-fold in silica-treated lungs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alterations in the pulmonary microsomal cytochrome P-450 system after exposure of rats to silica. 839 26

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.
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PMID:Pulmonary microsomal metabolism of benzo[a]pyrene following exposure of rats to silica. 875 37