Ultraviolet (UV) radiation causes potentially mutagenic DNA damage in skin cells. Our previous studies in human subjects showed photoprotective effects of topical 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3), applied before irradiation, on thymine dimers (TD), but the mechanisms were unclear. The aim of this study was to assess the activity of post-UV 1,25(OH)2D3 in human volunteers and to determine if one DNA repair mechanism (nucleotide excision repair- NER) is modulated by 1,25(OH)2D3. Volunteers were exposed to solar-simulated UV close to the MED, followed immediately by treatment with topical 1,25(OH)2D3, or vehicle. In punch biopsies taken 2h later, DNA damage and expression of DNA repair enzymes were analysed by immunohistochemistry and image analysis using antibodies to 3 types of DNA damage: TD, 8-oxo-7,8-dihydroguanine (8-oxodG), and 8-nitroguanosine (8-NG), and 2 types of NER proteins, Xeroderma Pigmentosum complementation group C (XPC) and DNA damage binding protein 2 (DDB2).
1,25(OH)2D3 reduced UV-induced TD by 57%, 8-oxodG by 51%, and 8-NG by 41%. At the same time, 1,25(OH)2D3 increased XPC by 146% and DDB2 by 97%. The data is consistent with the proposal that improved efficiency of NER may be one of the mechanisms explaining the photoprotective effects of 1,25(OH)2D3 in skin.
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