title: 1α,25-Dihydroxyvitamin D3 reduces several types of UV-induced DNA damage and contributes to photoprotection.
abstract: Vitamin D production requires UVB. In turn, we have shown that vitamin D compounds reduce UV-induced damage, including inflammation, sunburn, thymine dimers, the most frequent type of cyclobutane pyrimidine dimer, immunosuppression, and photocarcinogenesis. Our previous studies have shown most of the photoprotective effects by 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) occurred through the nongenomic pathway because similar protection was seen with an analog, 1α,25-dihydroxylumistrol3 (JN), which has little ability to alter gene expression and also because a nongenomic antagonist of 1,25(OH)2D3 abolished protection. In the current study, we tested whether this photoprotective effect would extend to other types of DNA damage, and whether this could be demonstrated in human ex vivo skin, as this model would be suited to pre-clinical testing of topical formulations for photoprotection. In particular, using skin explants, we examined a time course for thymine dimers (TDs), the most abundant DNA photolesion, as well as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), which is a mutagenic DNA base lesion arising from UV-induced oxidative stress, and 8-nitroguanosine (8-NG). Nitric oxide products, known markers for chronic inflammation and carcinogenesis, are also induced by UV. This study showed that 1,25(OH)2D3 significantly reduced TD and 8-NG as early as 30min post UV, and 8-oxodG at 3h post UV, confirming the photoprotective effect of 1,25(OH)2D3 against DNA photoproducts in human skin explants. At least in part, the mechanism of photoprotection by 1,25(OH)2D3 is likely to be through the reduction of reactive nitrogen species and the subsequent reduction in oxidative and nitrosative damage. This article is part of a Special Issue entitled 'Vitamin D Workshop'.
authors.affiliation: Department of Physiology and Bosch Institute, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Song
authors.forename: Clare
authors.initials: C
authors.lastname: Gordon-Thomson
authors.forename: Louise
authors.initials: L
authors.lastname: Cole
authors.forename: Harvey
authors.initials: H
authors.lastname: Stern
authors.forename: Gary M
authors.initials: GM
authors.lastname: Halliday
authors.forename: Diona L
authors.initials: DL
authors.lastname: Damian
authors.forename: Vivienne E
authors.initials: VE
authors.lastname: Reeve
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Mason
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D002117:Calcitriol / Q000494:pharmacology*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006151:Guanosine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D009574:Nitro Compounds / Q000378:metabolism; D011740:Pyrimidine Dimers / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D013473:Sunscreening Agents / Q000494:pharmacology*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: C481144:8-nitroguanosine; D009574:Nitro Compounds; D011740:Pyrimidine Dimers; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D013473:Sunscreening Agents; D006151:Guanosine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002117:Calcitriol; D003849:Deoxyguanosine