1. Prolonged particulate hexavalent chromium exposure induces RAD51 foci inhibition and cytoplasmic accumulation in immortalized and primary human lung bronchial epithelial cells.
- Author
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Meaza, Idoia, Williams, Aggie R., Lu, Haiyan, Kouokam, J. Calvin, Toyoda, Jennifer H., Croom-Perez, Tayler J., Wise, Sandra S., Aboueissa, Abou El-Makarim, and Wise, John Pierce
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LUNGS , *HEXAVALENT chromium , *EPITHELIAL cells , *DOUBLE-strand DNA breaks , *SISTER chromatid exchange , *ZINC - Abstract
Hexavalent chromium [Cr(VI)] is a human lung carcinogen with widespread exposure risks. Cr(VI) causes DNA double strand breaks that if unrepaired, progress into chromosomal instability (CIN), a key driving outcome in Cr(VI)-induced tumors. The ability of Cr(VI) to cause DNA breaks and inhibit repair is poorly understood in human lung epithelial cells, which are extremely relevant since pathology data show Cr(VI)-induced tumors originate from bronchial epithelial cells. In the present study, we considered immortalized and primary human bronchial epithelial cells. Cells were treated with zinc chromate at concentrations ranging 0.05 to 0.4μg/cm2 for acute (24 h) and prolonged (120 h) exposures. DNA double strand breaks (DSBs) were measured by neutral comet assay and the status of homologous recombination repair, the main pathway to fix Cr(VI)-induced DSBs, was measured by RAD51 foci formation with immunofluorescence, RAD51 localization with confocal microscopy and sister chromatid exchanges. We found acute and prolonged Cr(VI) exposure induced DSBs. Acute exposure induced homologous recombination repair, but prolonged exposure inhibited it resulting in chromosome instability in immortalized and primary human bronchial epithelial cells. [Display omitted] • Cr(VI) is genotoxic to primary and immortalized human bronchial epithelial cells. • Acute Cr(VI) induces DNA breaks and their repair in human lung epithelial cells. • Prolonged Cr(VI) exposure induces DNA breaks in human bronchial epithelial cells. • Prolonged Cr(VI) exposure inhibits repair in human bronchial epithelial cells. • Particulate Cr(VI) induces chromosome instability in human bronchial epithelial cells. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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