Photoprotection by 1,25 dihydroxyvitamin D3 is associated with an increase in p53 and a decrease in nitric oxide products

Vitamin D is produced in skin by UVB radiation (290-320 nm) acting on 7-dehydrocholesterol. The hypotheses that the active vitamin D hormone, 1,25 dihydroxyvitamin D-3 (1,25(OH)(2)D-3), would increase the survival of skin cells after UV irradiation and that surviving cells after 1,25(OH)(2)D-3 treatment would have no increase in DNA damage were tested. The survival of keratinocytes post-UVR was significantly greater after treatment with 1,25(OH)(2)D-3 compared to vehicle (P < 0.01). Significant reductions in thymine dimers (TDs) in surviving keratinocytes after UVR were noted in the presence of 1,25(OH)(2)D-3 (P < 0.001). Nuclear p53 protein expression increased after UVR and was significantly higher in keratinocytes treated with 1,25(OH)(2)D-3 (P < 0.01), whereas NO products were significantly reduced (P < 0.05). Both the increase in nuclear accumulation of p53 protein and reduced formation of nitric oxide products may contribute to the reduction in TDs seen with 1,25(OH)(2)D-3 after UVR. Reductions in numbers of sunburn cells (P < 0.01) and in TDs (P < 0.05) were observed 24 hours after UVR in skin sections from Skh:hr1 mice treated with 1,25(OH)(2)D-3. These results are consistent with the proposal that the vitamin D system in skin may be part of an intrinsic protective mechanism against UV damage.