Oral Presentation 6th Australian Health and Medical Research Congress 2012

Differential photoprotective effects of 1,25-dihydroxyvitamin D3 and a low calcaemic deltanoid (#166)

Katie M Dixon 1 , Vanessa B Sequeira 1 , Shivashni S Deo 1 , Ritu Mohan 1 , Gary H Posner 2 , Vivienne E Reeve 3 , Rebecca S Mason 1
  1. Discipline of Physiology, Bosch Institute, University of Sydney, Sydney, NSW, Australia
  2. Department of Chemistry, School of Arts and Sciences, Johns Hopkins University, Baltimore, MD, USA
  3. Faculty of Veterinary Sciences, University of Sydney, Sydney, NSW, Australia

We previously demonstrated that the active vitamin D hormone, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) and a cis-locked non-genomic analogue, protect skin cells from ultraviolet radiation (UV)-induced skin cell loss, DNA damage, immunosuppression and skin carcinogenesis. Here, we used low calcaemic analogue, 1α-hydroxymethyl-16-ene-24,24-difluoro-25-hydroxy-26,27-bis-homovitaminD3 (QW), which has some transactivating capacity and is approximately 80-100X less calcaemic than 1,25(OH)2D3. QW (0.1 – 10 nM) significantly (p < 0.05 - 0.01) reduced UV-induced DNA lesions (CPD) in skin fibroblasts and keratinocytes and reduced cell death after UV. Moreover, both 1,25(OH)2D3 and QW (1 nM) were equally effective in significantly (p < 0.01) increasing levels of tumour suppressive p53 in cultured human keratinocytes at 3 and 6 h after UV. In a hairless mouse model, both 1,25(OH)2D3 and QW (22.8 ρmol/cm2) reduced UV-immunosuppression from 13.7 ± 1.3 %. to 0.1 ± 1.1 % (p < 0.01) and 5.4 ± 1.5 % (p < 0.01) respectively. When tested alongside 1,25(OH)2D3 in a murine model of skin carcinogenesis. QW (22.8 ρmol/cm2) was not as effective as 1,25(OH)2D3 or a cis-locked analogue in reducing tumour formation or inhibiting tumour progression. It is possible that the dose required for QW to be effective as an anti-photocarcinogenesis agent in vivo is higher than for protection against the acute effects of UV, but the dissociation between clear acute photo-protective effects and limited long term photoprotection is as yet unexplained.