Singh J, Pritchard D E, Carlisle D L, Mclean J A, Montaser A, Orenstein J M, Patierno S R
Department of Pharmacology, The George Washington University Medical Center, Washington, D.C., 20037, USA.
Toxicol Appl Pharmacol. 1999 Dec 15;161(3):240-8. doi: 10.1006/taap.1999.8816.
Occupational exposure to certain particulate hexavalent chromium [Cr(VI)] compounds, such as lead chromate, has been associated with lung cancer and respiratory tract toxicity. We have previously shown that apoptosis is a major mode of death in cultured rodent cells treated with soluble sodium chromate and particulate lead chromate. Here we report the cellular and molecular effects of lead chromate and sodium chromate in normal human lung small airway epithelial (HSAE) cells, which may be one of the targets for Cr(VI)-induced lung cancer and respiratory tract toxicity. Phagocytosed lead chromate particles and intracellular lead-inclusion bodies (LIB) were observed by transmission electron microscopy and confirmed by X-ray analysis. HSAE cells exposed to lead chromate and sodium chromate underwent dose-dependent apoptosis. The cellular uptake and genomic interactions of both Cr and lead (Pb) were examined by inductively coupled plasma mass spectrometry (ICPMS) coupled with a novel, direct-injection high-efficiency nebulizer (DIHEN). Using this approach, we have quantitated a dose-dependent formation of Cr-DNA adducts and DNA-associated Pb in lead chromate-treated HSAE cells. The formation of LIB in normal human lung cells exposed to lead chromate indicates that ionic Pb is released from the particles and thus might contribute to the cell toxicity caused by lead chromate. Internalization and dissolution of lead chromate particles and the interaction of ionic Cr and Pb with DNA, may be components of the mechanism of lead chromate carcinogenesis. Lead chromate-induced apoptosis may be a mechanism to eliminate cells with chromium- and/or lead-damaged DNA.
职业接触某些颗粒状六价铬[Cr(VI)]化合物，如铬酸铅，已被证实与肺癌和呼吸道毒性有关。我们之前已经表明，凋亡是经可溶性铬酸钠和颗粒状铬酸铅处理的培养啮齿动物细胞中的主要死亡方式。在此，我们报告铬酸铅和铬酸钠对正常人肺小气道上皮（HSAE）细胞的细胞和分子效应，HSAE细胞可能是Cr(VI)诱导的肺癌和呼吸道毒性的靶细胞之一。通过透射电子显微镜观察到吞噬的铬酸铅颗粒和细胞内铅包涵体（LIB），并通过X射线分析得以证实。暴露于铬酸铅和铬酸钠的HSAE细胞发生了剂量依赖性凋亡。采用电感耦合等离子体质谱（ICPMS）结合新型直接进样高效雾化器（DIHEN）检测Cr和铅（Pb）的细胞摄取及基因组相互作用。运用该方法，我们已定量分析了铬酸铅处理的HSAE细胞中Cr-DNA加合物和与DNA相关的Pb的剂量依赖性形成。暴露于铬酸铅的正常人肺细胞中LIB的形成表明离子态Pb从颗粒中释放出来，因此可能是铬酸铅导致细胞毒性的原因之一。铬酸铅颗粒的内化和溶解以及离子态Cr和Pb与DNA的相互作用，可能是铬酸铅致癌机制的组成部分。铬酸铅诱导的凋亡可能是一种消除具有铬和/或铅损伤DNA细胞的机制。
