Comparative genotoxicity and cytotoxicity of four hexavalent chromium compounds in human bronchial cells.

Hexavalent chromium (Cr(VI)) compounds are well-established human lung carcinogens. Solubility plays an important role in their carcinogenicity with the particulate Cr(VI) compounds being the most carcinogenic. Epidemiology and animal studies suggest that zinc chromate is the most potent particulate Cr(VI) compound; however, there are few comparative data to support these observations. The purpose of this study was to compare the genotoxicity of zinc chromate with two other particulate Cr(VI) compounds, barium chromate and lead chromate, and one soluble Cr(VI) compound, sodium chromate. The clastogenic effects of barium chromate and zinc chromate were similar, but lead chromate induced significantly less damage. The levels of DNA damage measured by gamma-H2A.X foci formation were similar for the three particulate chromium compounds. Corrected for chromium uptake differences, we found that zinc chromate and barium chromate were the most cytotoxic, and lead chromate and sodium chromate were less cytotoxic. Zinc chromate was more clastogenic than all other chromium compounds, and lead chromate was the least clastogenic. There was no significant difference between any of the compounds for the induction of DNA double strand breaks. All together, these data suggest that the difference in the carcinogenic potency of zinc chromate over the other chromium compounds is not due solely to a difference in chromium ion uptake and that the zinc cation may in fact have an important role in its carcinogenicity.

Comparison of two particulate hexavalent chromium compounds: Barium chromate is more genotoxic than lead chromate in human lung cells.

Particulate hexavalent chromium [Cr(VI)] compounds are well-established human lung carcinogens. However, their carcinogenic mechanisms are poorly understood as most investigators have used soluble Cr(VI) compounds. Recent work from our laboratory has found that barium chromate (BC) is also cytotoxic and clastogenic. To understand how BC relates to existing data on other particulate Cr(VI) compounds, we compared its cytotoxicity and clastogenicity with lead chromate (LC), which has been used as a prototypical particulate Cr(VI) compound, in WTHBF-6 cells, a near-normal human lung cell line. We found that BC is a more potent cytotoxicant, inducing 67%, 12%, 3%, and 0% relative survival at concentrations of 0.1, 0.5, 1, and 5 microg/cm2, respectively, while LC induced 90%, 71%, 43%, and 15% survival at these same concentrations. We found that BC was also more clastogenic, damaging 22% and 49% of metaphase cells at 0.1 and 0.5 microg/cm2, and causing complete cell cycle arrest at 1 and 5 microg/cm2. By contrast, 0.1, 0.5, and 1.0 microg/cm2 LC damaged 10%, 27%, and 37% of metaphase cells, respectively, and complete cell cycle arrest was not observed until a concentration of 5 microg/cm2 was reached. We found that BC and LC both partially dissolved in complete medium in the presence of cells, producing similar extracellular concentrations. Both compounds were also comparable with respect to particle uptake and the amount of intracellular Cr ions. Considering previous reports showing that lead ions were inactive and that sodium chromate and LC have similar clastogenic potencies, these data suggest that BC genotoxicity may not be solely mediated by Cr ions, but also involve some clastogenic activity of barium ions.

Barium chromate is cytotoxic and genotoxic to human lung cells.

Hexavalent chromium (Cr(VI)) compounds are widely accepted as human lung carcinogens. However, there have been few investigations of the genotoxicity of Cr(VI) in human lung cells. Moreover, our knowledge of the effects of Cr(VI) in human lung cells is further limited because the available data generally focus on the effects of only lead chromate (PbCrO(4)) and sodium chromate (Na(2)CrO(4)). To fully understand these carcinogenic compounds, the genotoxic effects to its target cells need to be evaluated for additional Cr(VI) salts. Accordingly, we investigated the cytotoxicity and clastogenicity of barium chromate (BC) in a human lung cell culture model (WTHBF-6 cells). We found that BC induced concentration-dependent cytotoxicity in WTHBF-6 cells, with relative survival of 88%, 74%, 67%, 12%, 3%, and 0.1% after exposure to 0.01, 0.05, 0.1, 0.5, 1, and 5 microg/cm(2) BC, respectively. Similarly, the amount of chromosomal damage also increased with concentration after a 24-h exposure. Specifically, 0.01, 0.05, 0.1, and 0.5 microg/cm(2) BaCrO(4) damaged 5%, 9%, 22%, and 49% of metaphase cells, with the total damage reaching 5, 10, 28, and 65 aberrations per 100 metaphases, respectively. Concentrations of 1 and 5 microg/cm(2) BC induced a profound cell cycle delay, and no metaphases were observed. The spectrum of damage included chromatid and chromosome-type lesions consistent with mechanistic events associated with the activation of oncogenes and inactivation of tumor suppressor genes. Overall the data indicate that BC is cytotoxic and genotoxic to human lung cells.