Alterations in the Pulmonary Microsomal Cytochrome P-450 System after Exposure of Rats to Silica

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Abstract
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)