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 (302 nm) and UVA (368 nm) 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.
Department of Chemistry and Biochemistry, Northern Arizona University, Flagstaff, AZ, USA.
Janice
J
Wilson
Mary C
MC
Zuniga
Filbert
F
Yazzie
Diane M
DM
Stearns
D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003043:Cocarcinogenesis; D003412:Cricetulus; D004247:DNA / Q000187:drug effects* / Q000528:radiation effects; D018736:DNA Adducts / Q000187:drug effects / Q000528:radiation effects; D053904:DNA Breaks, Single-Stranded; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D006358:Hot Temperature / Q000009:adverse effects; D006801:Humans; D007202:Indicators and Reagents / Q000737:chemistry; D015603:Keratinocytes / Q000187:drug effects / Q000528:radiation effects; D009153:Mutagens / Q000528:radiation effects* / Q000633:toxicity; D009942:Organometallic Compounds / Q000528:radiation effects* / Q000633:toxicity; D055668:Photochemical Processes; D010880:Piperidines / Q000737:chemistry; D010957:Plasmids / Q000187:drug effects* / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*
D018736:DNA Adducts; D007202:Indicators and Reagents; D009153:Mutagens; D009942:Organometallic Compounds; D010880:Piperidines; C005460:uranyl acetate; C032727:piperidine; D004247:DNA
DNA damage; DNA repair; Depleted uranium; cell culture; plasmid DNA