Photoprotection by 1α,25-dihydroxyvitamin D and analogs: Further studies on mechanisms and implications for UV-damage

Ultraviolet (UV) irradiation causes DNA damage in skin cells, immunosuppression and photocarcinogenesis. 1α,25-dihydroxyvitamin D3 (1,25D) reduces UV-induced DNA damage in the form of cyclobutane pyrimidine dimers (CPD) in human keratinocytes in culture and in mouse and human skin. UV-induced immuno...

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Bibliographic Details
Published in:	Journal of steroid biochemistry and molecular biology Vol. 121; no. 1; pp. 164 - 168
Main Authors:	Mason, R.S., Sequeira, V.B., Dixon, K.M., Gordon-Thomson, C., Pobre, K., Dilley, A., Mizwicki, M.T., Norman, A.W., Feldman, D., Halliday, G.M., Reeve, V.E.
Format:	Journal Article Conference Proceeding
Language:	English
Published:	Kidlington Elsevier Ltd 01-07-2010 Elsevier
Subjects:	1α,25-Dihydroxyvitamin D3 Biological and medical sciences Cancer Fundamental and applied biological sciences. Psychology Photoprotection Ultraviolet radiation Vertebrates: endocrinology Vertebrates: reproduction Ultraviolet radiation 1α,25-Dihydroxyvitamin D3 Photoprotection Cancer Malignant tumor Analog
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Summary:	Ultraviolet (UV) irradiation causes DNA damage in skin cells, immunosuppression and photocarcinogenesis. 1α,25-dihydroxyvitamin D3 (1,25D) reduces UV-induced DNA damage in the form of cyclobutane pyrimidine dimers (CPD) in human keratinocytes in culture and in mouse and human skin. UV-induced immunosuppression is also reduced in mice by 1,25D, in part due to the reduction in CPD and a reduction in interleukin (IL-6. The cis-locked analog, 1α,25-dihydroxylumisterol3 (JN), which has almost no transactivating activity, reduces UV-induced DNA damage, apoptosis and immunosuppression with similar potency to 1,25D, consistent with a non-genomic signalling mechanism. The mechanism of the reduction in DNA damage in the form of CPD is unclear. 1,25D doubles nuclear expression of p53 compared to UV alone, which suggests that 1,25D facilitates DNA repair. Yet expression of a key DNA repair gene, XPG is not affected by 1,25D. Chemical production of CPD has been described. Incubation of keratinocytes with a nitric oxide donor, SNP, induces CPD in the dark. We previously reported that 1,25D reduced UV-induced nitrite in keratinocytes, similar to aminoguanidine, an inhibitor of nitric oxide synthase. A reduction in reactive nitrogen species has been shown to facilitate DNA repair, but in view of these findings may also reduce CPD formation via a novel mechanism.
ISSN:	0960-0760 1879-1220
DOI:	10.1016/j.jsbmb.2010.03.082