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Title: 1,25-Dihydroxyvitamin D3 and analogues protect primary human keratinocytes against UVB-induced DNA damage
Authors: De Haes, Petra
Garmyn, Maria
Verstuyf, Annemieke
De Clercq, Pierre
Vandewalle, Maurits
Degreef, Hugo
Vantieghem, Katleen
Bouillon, Roger
Segaert, Siegfried # ×
Issue Date: Feb-2005
Publisher: Elsevier Sequoia
Series Title: Journal of Photochemistry and Photobiology B, Biology vol:78 issue:2 pages:141-148
Abstract: Exposure to UVB irradiation is a major risk factor for the development of skin cancer. Therefore, it is important to identify agents that can offer protection against UVB-caused damage. Photocarcinogenesis is caused largely by mutations at sites of incorrectly repaired DNA photoproducts, of which the most common are the cyclobutane pyrimidine dimers (CPDs). In this study, we demonstrated that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] protects primary human keratinocytes against the induction of CPDs by UVB. This protection required pharmacologic doses 1,25(OH)2D3 and an incubation period of at least 8 h before irradiation. Furthermore, we provided arguments indicating that the anti-proliferative capacity of 1,25(OH)2D3 underlies its protective effect against UVB-induced DNA damage. Finally, we showed that 19-nor-14-epi-23-yne-1,25(OH)2D3 (TX 522) and 19-nor-14,20-bisepi-23-yne-1,25(OH)2D3 (TX 527), two low-calcemic analogues of 1,25(OH)2D3, were even 100 times more potent than the parent molecule in inhibiting UVB-caused DNA damage. These molecules are therefore promising candidates for the chemoprevention of UVB-induced skin cancer.
URI: 
ISSN: 1011-1344
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Dermatology
Clinical and Experimental Endocrinology
Laboratory of Dermatoimmunology (+)
× corresponding author
# (joint) last author

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