Lead ions do not cause human lung cells to escape chromate-induced cytotoxicity
Lead ions do not cause human lung cells to escape chromate-induced cytotoxicity
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DOI：
10.1016/j.taap.2004.08.006
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发表时间：
2005-03-01
影响因子：
3.8
通讯作者：
Wise, JP
中科院分区：
文献类型：
--
作者：
Holmes, AL;Wise, SS;Wise, JP
六价铬(六价铬)化合物是公认的人类肺癌致癌物：溶解度在铬(六价铬)致癌性中起着关键作用，最强的致癌物是水不溶或颗粒物。铬酸铅被用作典型的颗粒状铬(VI)化合物，因为它是这些化合物中最难溶的。我们实验室以前的工作表明，铬酸铅颗粒在细胞外溶解，产生铬(Cr)和铅(Pb)离子，并且铬离子具有遗传毒性。PB被假设在铬酸铅的致癌活性中起表观遗传作用，可能是通过允许铬损伤的细胞存活，然而，这种可能性还没有被调查。因此，我们确定了铅和铬离子在铬酸铅诱导的克隆存活中的功能作用。我们发现，维生素C共处理消除了铬离子的摄取，对铅离子水平只有轻微的影响，并消除了铬酸铅的细胞毒性。这些数据表明，细胞毒性是由铬离子引起的。我们发现铬酸铅和可溶性铬(VI)诱导的细胞毒性相当，说明铅不起表观遗传作用，不能使铬损伤的细胞存活。(C)2004 Elsevier Inc.保留所有权利。
Hexavalent chromium (Cr (VI)) compounds are established human lung carcinogens: Solubility plays a key role in Cr (VI) carcinogenicity, with the most potent carcinogens being water-insoluble or `particulate'. Lead chromate is used as the prototypical particulate Cr (VI) compound since it is the most insoluble of these compounds. Previous work in our laboratory showed that lead chromate particles dissolve outside cells to produce chromium (Cr) and lead (Pb) ions and that the Cr ions were genotoxic. Pb has been hypothesized to play an epigenetic role in the carcinogenic activity of lead chromate, perhaps by allowing Cr-damaged cells to survive, however, this possibility has not been investigated. Accordingly, we determined the functional role of Pb and Cr ions in lead chromate-induced clonogenic survival. We found that vitamin C co-treatment eliminated Cr ion uptake, had only a slight effect on Pb ion levels, and eliminated lead chromate cytotoxicity. These data indicate that Cr ions caused the cytotoxicity. We found that lead chromate and soluble Cr (VI) induced similar amounts of cytotoxicity indicating that Pb does not play an epigenetic role and cause Cr-damaged cells to survive. (C) 2004 Elsevier Inc. All rights reserved.