title: Oxidatively-generated damage to DNA and proteins mediated by photosensitized UVA.
abstract: UVA accounts for about 95% of the solar ultraviolet (UV) radiation that reaches Earth and most likely contributes to human skin cancer risk. In contrast to UVB, which comprises the remaining 5% and is absorbed by DNA nucleobases to cause direct photodamage, UVA damages DNA indirectly. It does this largely through its interactions with cellular chromophores that act as photosensitisers to generate reactive oxygen species. Exogenously supplied chemicals, including some widely-prescribed medicines, may also act as photosensitisers and these drugs are associated with an increased risk of sun-related cancer. Because they amplify the effects of UVA on cells, they provide a means to investigate the mechanisms and effects of UVA-induced photodamage. Here, we describe some of the major lesions induced by two groups of UVA photosensitisers, the DNA thionucleotides and the fluoroquinolone antibiotics. In thionucleotides, replacement of the oxygen atoms of canonical nucleobases by sulfur converts them into strong UVA chromophores that can be incorporated into DNA. The fluoroquinolones are also UVA chromophores. They are not incorporated into DNA and induce a different range of DNA damages. We also draw attention to the potentially important contribution of photochemical protein damage to the cellular effects of photosensitised UVA. Proteins targeted for oxidation damage include DNA repair factors and we suggest that UVA-mediated protein damage may contribute to sunlight-induced cancer risk.
authors.affiliation: The Francis Crick Institute, 1, Midland Road, London NW1 1AT, UK.
authors.forename: Reto
authors.initials: R
authors.lastname: Brem
authors.affiliation: The Francis Crick Institute, 1, Midland Road, London NW1 1AT, UK.
authors.forename: Melisa
authors.initials: M
authors.lastname: Guven
authors.affiliation: The Francis Crick Institute, 1, Midland Road, London NW1 1AT, UK. Electronic address: peter.karran@crick.ac.uk.
authors.forename: Peter
authors.initials: P
authors.lastname: Karran
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000627:therapeutic use; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair; D024841:Fluoroquinolones / Q000737:chemistry* / Q000627:therapeutic use; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D013873:Thionucleotides / Q000737:chemistry* / Q000627:therapeutic use; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D013873:Thionucleotides; D004247:DNA
keywords: DNA lesions; Photosensitizer; Protein oxidation; Thiopurines; Thiopyrimidines; UVA