Lead ions do not cause human lung cells to escape chromate-induced cytotoxicity

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.