1α,25-Dihydroxyvitamin D₃ Modulates the Response of Human Keratinocytes to Ionizing Radiation Exposure

Abstract

Background: Exposure of human skin to ionizing radiation may result in various effects such as inflammation, keratosis, fibrosis and cancer. 1α,25-Dihydroxyvitamin D₃ (1α,25(OH)₂D₃), the biologically active metabolite of vitamin D, has been shown to exert pleiotropic effects on the skin. The aim of the study was to evaluate the effect of 1α,25(OH)₂D₃ on the radiation response of human keratinocytes. Materials and Methods: Keratinocytes (HaCaT), either untreated or pretreated with 1α,25(OH)₂D₃, were irradiated with 0-7.5 Gy. Growth curves were generated to determine cell proliferation. Cell survival was examined using a clonogenic assay. The cell surface expression of adhesion molecules was investigated by flow cytometry. Results: The cell growth and clonogenic survival of irradiated keratinocytes were both significantly increased by 1α,25(OH)₂D₃. Ionizing radiation caused an up-regulation of the cell surface expression of intercellular adhesion molecule-1 (ICAM-1) and integrins beta1 (CD29), alpha2 (CD49b), alpha5 (CD49e) and alpha6 (CD49f) in keratinocytes, which was inhibited by 1α,25(OH)₂D₃. Conclusion: The data suggest that 1α,25(OH)₂D₃ may be a promising agent to modify the radiation reaction, thus offering new options in radiotherapy and oncology.