title: UV-A induces persistent genomic instability in human keratinocytes through an oxidative stress mechanism.
abstract: Ultraviolet-A (UV-A, 320 to 400 nm) radiation comprises 95% of the solar ultraviolet radiation (UVR) reaching the earth's surface. It has been associated experimentally and epidemiologically with malignant melanoma. In this study we investigated whether UV-A radiation can induce a persistent, heritable hypermutability in mammalian cells similar to that observed following ionising radiation (IR). Using the immortalized human skin keratinocyte cell line HaCaT we found that UV-A radiation does lead to a continuing reduction in plating efficiency, an increased "spontaneous" mutant fraction, and an increase in micronucleus formation up to 21 d after initial exposure. Reversal of these effects using catalase may indicate a role for hydrogen peroxide in this phenomenon. These results add to the significance of UV-A radiation as a risk factor in skin carcinogenesis.
authors.affiliation: Department of Biological Sciences, Lancaster University, Bailrigg, UK.
authors.forename: Ross P
authors.initials: RP
authors.lastname: Phillipson
authors.forename: Simon E
authors.initials: SE
authors.lastname: Tobi
authors.forename: James A
authors.initials: JA
authors.lastname: Morris
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: McMillan
mesh_terms: D002374:Catalase / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured / Q000528:radiation effects*; D003114:Colony-Forming Units Assay; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects*; D009154:Mutation / Q000528:radiation effects; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics*; D013482:Superoxide Dismutase / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase