Background: Although the incidence of non-melanoma skin cancer is increasing, there are no effective practical preventive measures other than avoiding sun exposure. Objective: To elucidate the protective effect of topical application of biologically active vitamin D3 (calcitriol) on skin cancer development caused by exposure to ultraviolet (UV). Methods: Groups of hairless mice were topically treated with either calcitriol or vehicle immediately after exposure to UVB and UVA three times weekly for the initial 20 weeks, and without UV exposure in the following 6 weeks. Tumor number was counted and biopsies were done for histopathologic analysis. The changes of cyclobutane pyrimidine dimer (CPD) were evaluated 1 hour and 11 hours after short term of UV exposure and application of calcitriol. For safety evaluation, blood test and body weights were evaluated at 23rd and 25th week. Results: Total tumor count and number of tumors less than 3 mm in size tended to be fewer in calcitriol group, and tumors more than 3 mm in size showed significantly lower tumor formation rate in calcitriol group. Single application of calcitriol reduced CPD at 1 hour and 11 hours after UV exposure. Histopathologic analysis showed tumors with lower grade malignancy in calcitriol group which suggested a delay in tumor progression. However, serum levels of calcium and phosphate in calcitriol group were above normal range, and weight loss was found. Conclusion: Topical calcitriol may suppress the formation and progression of UV-induced non-melanoma skin cancer by enhancing the repair mechanism of UV damage.
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