Miles P R, Bowman L, Jones W G, Berry D S, Vallyathan V
Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505.
Toxicol Appl Pharmacol. 1994 Dec;129(2):235-42. doi: 10.1006/taap.1994.1248.
Intratracheal exposures of rats to crystalline silica washed with HCl to remove iron contaminants have previously been shown to increase lung surfactant phospholipids (PL) and proteins and to alter the pulmonary 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 and alveolar lavage PL and proteins, but to different degrees. The increases produced by HCl-washed vs unwashed silica are lung weights, 2.2- vs 1.3-fold; lavage PL, 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-fold increase in 7-ethoxyresorufin O-deethylation, a reaction catalyzed by cytochrome P4501A1, and a 0.5- to 0.6-fold reduction in 7-ethoxycoumarin O-deethylation, a reaction which may be catalyzed by cytochrome P-4502B1. Unwashed silica does not alter the metabolism of either xenobiotic when results are expressed per milligram microsomal protein. Administration of alumina produces only minor increases in lung weight and lavage PL and no effect on microsomal xenobiotic metabolism. These results show that the increases in alveolar lavage PL and proteins induced by administration of unwashed silica are exaggerated by 3- to 7-fold if the silica is treated with HCl. Furthermore, exposure to HCl-washed silica results in significant alterations of the lung microsomal cytochrome P450 system, but the unwashed silica has little effect. Although the reason(s) for these different effects is not known, measurements of iron levels and formation of hydroxyl radicals using ESR demonstrate that there is more iron associated with the unwashed than with the HCl-washed silica.
先前的研究表明，将大鼠经气管暴露于用盐酸洗涤以去除铁污染物的结晶二氧化硅中，会增加肺表面活性物质磷脂（PL）和蛋白质，并改变肺微粒体细胞色素P450系统。我们比较了盐酸洗涤过的二氧化硅与未洗涤的二氧化硅和氧化铝暴露所产生的这些影响。两种二氧化硅制剂都会使肺重量以及肺泡灌洗中的PL和蛋白质增加，但程度不同。盐酸洗涤过的二氧化硅与未洗涤的二氧化硅相比，肺重量增加倍数分别为2.2倍和1.3倍；灌洗PL增加倍数分别为25.9倍和3.7倍；灌洗蛋白质增加倍数分别为11.1倍和3.2倍。尽管两种二氧化硅颗粒都会使肺微粒体蛋白质浓度（每克肺计算）增加50%至60%，但它们对细胞色素P-450介导的外源性物质代谢的影响却大不相同。暴露于盐酸洗涤过的二氧化硅会导致7-乙氧基试卤灵O-脱乙基化增加2.3倍，该反应由细胞色素P4501A1催化，而7-乙氧基香豆素O-脱乙基化减少0.5至0.6倍，该反应可能由细胞色素P-4502B1催化。当以每毫克微粒体蛋白质计算结果时，未洗涤的二氧化硅不会改变任何一种外源性物质的代谢。给予氧化铝只会使肺重量和灌洗PL略有增加，对微粒体外源性物质代谢没有影响。这些结果表明，如果用盐酸处理二氧化硅，未洗涤的二氧化硅引起的肺泡灌洗PL和蛋白质增加会被夸大3至7倍。此外，暴露于盐酸洗涤过的二氧化硅会导致肺微粒体细胞色素P450系统发生显著改变，但未洗涤的二氧化硅影响很小。尽管尚不清楚产生这些不同影响的原因，但使用电子自旋共振（ESR）测量铁水平和羟基自由基的形成表明，与未洗涤的二氧化硅相比，与盐酸洗涤过的二氧化硅结合的铁更多。
