54. 1a,25-Dihydroxyvitamin D3 reduces several types of UV induced DNA damage in human ex vivo skin

Abstract

1α,25dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) is produced in skin following exposure to ultraviolet radiation (UVR). On the other hand, UVR can also cause DNA damage. Cyclobutane pyrimidine dimers (CPD) are produced as a direct consequence of UVB exposure. Other photolesions, such as 8-oxo-7,8-dihydroguanosine (8-oxodG) and 8-nitroguanine (8-NG) are produced by UV-induced oxidative and nitrosative stress. All these DNA lesions are potentially mutagenic and may lead to photocarcinogenesis unless repaired promptly through DNA repair processes. Nitric oxide products and reactive nitrogen species (RNS) are known to hinder DNA repair and promote carcinogenesis. Previous studies have shown that 1,25(OH) 2 D 3 and the analog 1α,25(OH) 2 -lumisterol (JN) protect skin cells from UV-induced DNA damage (CPD), immunosuppression and photocarcinogenesis in mice. 1 The aim of this study was to test whether topical application of 1,25(OH) 2 D 3 is also photoprotective in UV-irradiated human skin explants. UV-induced DNA damage was quantified by immunohistochemistry and image analysis using antibodies to 3 different types of DNA damage: CPD, 8-oxodG, and 8-NG. Quantification by image analysis showed 1,25(OH) 2 D 3 post-UVR, significantly reduced all 3 types of DNA damage. CPD was reduced by 57% (±SEM=2.6; p p p 2 D 3 (37% reduction; p p 2 D 3 reduces UV induced nitrosative stress in skin. This data suggests that 1,25(OH) 2 D 3 provides photoprotection in human ex vivo skin through reduction in UV induced CPD, oxidative and nitrosative stress.