gms | German Medical Science

Both UV- and ionizing radiation have been characterized as carcinogens that may induce malignant epithelial skin tumors, with UV-light being the most important environmental risk factor. Increase in phosphorylated histone H2AX (gH2AX) foci has been shown to signal the presence of DNA damage following ionizing radiation, in particular double strand breaks. UV-light does not directly produce DNA double-strand breaks but rather produces pyrimidine dimers and other photoproducts, that must be removed or bypassed to prevent arrest of the replication fork. We have now analyzed effects of the biologically active vitamin D metabolite 1,25-dihydroxyvitamin D3 on presence of pyrimidine dimers and phosphorylated gH2AX in non-malignant and malignant human Keratinocytes (HaCaT, SCL-1) following UV(100 J/m2 – 1000 J/m2)- and ionizing irradiation (IR, 1Gy – 5Gy).), respectively. Additionally, we analyzed cell proliferation, cell viability and the expression of key components of the vitamin D system (vitamin D receptor, 1OHase, 25OHase, 24OHase).

Our findings indicate that pretreatment with 1,25(OH)2D3 time- and dose-dependently: (I) results in increased cell viability following UV-B or IR, (II) modulates expression of key components of the vitamin D system, and (III) reduces the presence of pyrimidine dimers and gH2AX foci following UV-B and ionizing irradiation, respectively. Our data support the hypothesis that the local cutaneous production of 1,25-dihydroxyvitamin D3 may represent an evolutionary highly conserved endocrine system to prevent mutagenic damage induced by UV- or ionizing irradiation.