Synergistic cytotoxicity and DNA strand breaks in cells and plasmid DNA exposed to uranyl acetate and ultraviolet radiation

Depleted uranium (DU) has a chemical toxicity that is independent of its radioactivity. The purpose of this study was to explore the photoactivation of uranyl ion by ultraviolet (UV) radiation as a chemical mechanism of uranium genotoxicity. The ability of UVB (302nm) and UVA (368nm) radiation to photoactivate uranyl ion to produce single strand breaks was measured in pBR322 plasmid DNA, and the presence of adducts and apurinic/apyrimidinic sites that could be converted to single strand breaks by heat and piperidine was analyzed. Results showed that DNA lesions in plasmid DNA exposed to UVB- or UVA-activated DU were only slightly heat reactive, but were piperidine sensitive. The cytotoxicity of UVB-activated uranyl ion was measured in repair-proficient and repair-deficient Chinese hamster ovary cells and human keratinocyte HaCaT cells. The cytotoxicity of co-exposures of uranyl ion and UVB radiation was dependent on the order of exposure and was greater than co-exposures of arsenite and UVB radiation. Uranyl ion and UVB radiation were synergistically cytotoxic in cells, and cells exposed to photoactivated DU required different DNA repair pathways than cells exposed to non-photoactivated DU. This study contributes to our understanding of the DNA lesions formed by DU, as well as their repair. Results suggest that excitation of uranyl ion by UV radiation can provide a pathway for uranyl ion to be chemically genotoxic in populations with dermal exposures to uranium and UV radiation, which would make skin an overlooked target organ for uranium exposures. Copyright (c) 2014 John Wiley & Sons, Ltd. The photoactivation of uranyl ion by UV radiation was investigated as a chemical mechanism of uranium genotoxicity. The ability of UVB- and UVA-activated uranyl ion to generate strand breaks was measured in plasmid DNA, and the cytotoxicity of UVB-activated uranyl ion was measured in repair-proficient and repair-deficient Chinese hamster ovary cells, and human keratinocyte HaCaT cells. Results suggested that photoactivated uranyl ion is chemically genotoxic, and a case is made that skin is an overlooked target organ for uranium exposure.