CHANGES IN ALVEOLAR-LAVAGE MATERIALS AND LUNG MICROSOMAL XENOBIOTIC METABOLISM FOLLOWING EXPOSURES TO HCL-WASHED OR UNWASHED CRYSTALLINE SILICA

Intratracheal exposures of rats to crystalline silica washed with HCl to remove iron contaminants have previously been shown to increase lun g surfactant phospholipids (PL) and proteins and to alter the pulmonar y microsomal cytochrome P450 system. We compared these effects of HCl- washed silica with those produced by exposures to unwashed silica and alumina. Both silica preparations produce increases in lung weights an d alveolar lavage PL and proteins, but to different degrees. The incre ases produced by HCl-washed vs unwashed silica are lung weights, 2.2- vs 1.3-fold; lavage FL, 25.9- vs 3.7-fold; and lavage proteins, 11.1- vs 3.2-fold, respectively. Although the two silica particles increase lung microsomal protein concentrations (expressed per gram lung) by 50 -60%, their effects on cytochrome P-450-mediated xenobiotic metabolism are quite different. Exposure to HCl-washed silica leads to a 2.3-fol d increase in 7-ethoxyresorufin O-deethylation, a reaction catalyzed b y cytochrome P4501A1, and a 0.5- to 0.6-fold reduction in 7-ethoxycoum arin O-deethylation, a reaction which may be catalyzed by cytochrome P -4502B1. Unwashed silica does not alter the metabolism of either xenob iotic when results are expressed per milligram microsomal protein. Adm inistration of alumina produces only minor increases in lung weight an d lavage PL and no effect on microsomal xenobiotic metabolism. These r esults show that the increases in alveolar lavage PL and proteins indu ced by administration of unwashed silica are exaggerated by 3- to 7-fo ld if the silica is treated with HCl. Furthermore, exposure to HCl-was hed silica results in significant alterations of the lung microsomal c ytochrome P450 system, but the unwashed silica has little effect. Alth ough the reason(s) for these different effects is not known, measureme nts of iron levels and formation of hydroxyl radicals using ESR demons trate that there is more iron associated with the unwashed than with t he HCl-washed silica. (C) 1994 Academic Press, Inc.