Particulate hexavalent chromium (Cr(VI)) is a potent respiratory carcinogen with widespread human exposure. The particulate form, for example lead chromate, has been determined to be the most toxic and carcinogenic form. These particles impact at bifurcation sites of the lung and persist in the respiratory tract. Chromosome instability (CIN) is a hallmark of lung cancer with cells exhibiting both translocations and severe aneuploidy. However, the ability of Cr(VI) to induce translocations is unknown. We exposed human lung cells to lead chromate for three sequential 24 h periods, each separated by about a month. After each treatment, cells were seeded at colony forming density, cloned, expanded and retreated. Each generation of clones were tested for their chromium sensitivity, chromosome complement and DNA repair capacity. We found that after the first treatment, lead chromate-treated cells exhibited a normal chromosome complement though a few clones showed an increase in relative survival. After the second exposure, more than half of the clones acquired an abnormal karyotype including numerical and structural alterations. The third treatment resulted in more abnormal clones as well as previously abnormal clones acquiring additional abnormalities. Clones were also treated with soluble Cr(VI) for 24 h followed by a 24 h recovery period to measure DNA double strand break repair. Abnormal clones showed little or no reduction in H2A. X foci formation after 24 h recovery suggesting that these clones had acquired a DNA double strand break repair- deficient phenotype. This work was supported by NIEHS grant ES016893 (J.P.W.).

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3467.