1,25-dihydroxyvitamin D3 modulates effects of ionizing radiation (IR) on human keratinocytes: in vitro analysis of cell viability/proliferation, DNA-damage and -repair.

Abstract	We investigated the capacity of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) to protect spontaneously immortalized human keratinocytes (HaCaT) and cutaneous squamous cell carcinoma cells (SCL-1) against the hazardous effects of ionizing radiation (IR). We pretreated HaCaT and SCL-1 cells in vitro with 1,25(OH)2D3 (10(-7) M) over 48 h and then irradiated them once with IR (1 Gy, 2 Gy, and 5 Gy). Using WST-1-assay and crystal violet (CV) assay, we compared viability/proliferation in 1,25(OH)2D3-pretreated cells with controls that were pretreated with the carrier substance ethanol alone. Additionally, we analyzed the effects of 1,25(OH)2D3 on the presence of IR-induced DNA-damage by immunocytochemical detection of gamma-H2AX-foci in HaCaT-keratinocytes. We demonstrate that 1,25(OH)2D3 (10(-7) M) inhibits proliferation of human keratinocytes and that IR (1-5 Gy) has no significant effect on proliferation and viability of HaCaT-keratinocytes and SCL-1 cells. Moreover, we show that IR modulates dose-dependently the number of gammaH2AX-foci in HaCaT-keratinocytes. Pretreatment of the cells with 1,25(OH)2D3 reduces the number of IR-induced gammaH2AX-foci after irradiation with 1 Gy and 2 Gy and increases it after irradiation with 5 Gy. To put it in a nutshell, our data support the hypothesis that 1,25(OH)2D3 modulates the effects of low-dose IR (1-5 Gy) on cultured human keratinocytes.
Authors	Lea Trémezaygues, Markus Seifert, Thomas Vogt, Wolfgang Tilgen, Jörg Reichrath
Journal	The Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 121 Issue 1-2 Pg. 324-7 (Jul 2010) ISSN: 1879-1220 [Electronic] England
PMID	20214987 (Publication Type: Journal Article)
Copyright	Copyright (c) 2010 Elsevier Ltd. All rights reserved.
Chemical References	Calcitriol Gentian Violet
Topics	Calcitriol (metabolism) Carcinoma, Squamous Cell (metabolism) Cell Line Cell Line, Tumor Cell Proliferation Cell Survival DNA Damage DNA Repair Dose-Response Relationship, Radiation Gentian Violet (pharmacology) Humans In Vitro Techniques Keratinocytes (cytology, radiation effects) Models, Biological Radiation, Ionizing Time Factors

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