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Free Radic Biol Med. 2016 Oct 27. pii: S0891-5849(16)30961-3. doi: 10.1016/j.freeradbiomed.2016.10.488. [Epub ahead of print]

Oxidatively-generated damage to DNA and proteins mediated by photosensitized UVA.

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  • 1The Francis Crick Institute, Clare Hall Laboratory, South Mimms, Herts EN6 3LD. UK.
  • 2The Francis Crick Institute, Clare Hall Laboratory, South Mimms, Herts EN6 3LD. UK. Electronic address: peter.karran@crick.ac.uk.

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 sulphur 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.

KEYWORDS:

DNA lesions; UVA; photosensitizer; protein oxidation; thiopurines; thiopyrimidines

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