1alpha,25-Dihydroxyvitamin D3 modulates the response of human keratinocytes to ionizing radiation exposure.
BACKGROUND
Exposure of human skin to ionizing radiation may result in various effects such as inflammation, keratosis, fibrosis and cancer. 1alpha,25-Dihydroxyvitamin D3 (1alpha,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 1alpha,25(OH)2D3 on the radiation response of human keratinocytes.


METHODS
Keratinocytes (HaCaT), either untreated or pretreated with 1alpha,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 1alpha,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 1alpha,25(OH)2D3.


CONCLUSIONS
The data suggest that 1alpha,25(OH)2D3 may be a promising agent to modify the radiation reaction, thus offering new options in radiotherapy and oncology.
Müller
Kerstin
K
Bundeswehr Institute of Radiobiology, Neuherbergstr. 11, D-80937 Munich, Germany. kerstin2mueller@bundeswehr.org
Schinn
Michaela
M
Reichrath
Jörg
J
Meineke
Viktor
V
D002117:Calcitriol / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D048708:Cell Growth Processes / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D015854:Up-Regulation / Q000187:drug effects / Q000528:radiation effects
D015815:Cell Adhesion Molecules; D002117:Calcitriol