Abstract
Ultraviolet (UV) radiation induces a variety of biological effects, including DNA damage response and cell signaling pathways. We performed transcriptome analysis using microarray in human primary cultured fibroblasts irradiated with UV-C (0.5 or 5 J/m2) and harvested at 4 or 12 h following UV exposure. All transcript data were analyzed by comparison with the corresponding results in non-irradiated (control) cells. The number of genes with significantly altered expression (≥2-fold difference relative to the control) is higher in the sample irradiated with high dose of UV, suggesting that gene expression was UV dose-dependent. Pathway analysis on the upregulated genes at 12 h indicates that the expression of some cell cycle-related genes was predominantly induced irrespective of UV-dose. Interestingly, almost all the genes with significant altered expression were cell cycle-related genes designated as ‘Mitotic Genes’, which function in the spindle assembly checkpoint. Therefore, even a low dose of UV could affect the transcriptional profile.
Highlights
Well known pathways activated by DNA damage include a p53-dependent G1-phase checkpoint[3] and intra-S-phase ATR–CHK1-dependent checkpoint[4]
Primary cultured fibroblasts obtained from a 30 y.o. female healthy volunteer were irradiated with a low dose of UV-C, and subjected to microarray analysis
2% of all entities revealed altered expression in cells irradiated with low dose UV (LUV) at two time points
Summary
Well known pathways activated by DNA damage include a p53-dependent G1-phase checkpoint[3] and intra-S-phase ATR–CHK1 (ataxia telangiectasia and Rad3-related/checkpoint kinase 1)-dependent checkpoint[4]. In other cases UVR is known to induce the clustering of certain cell-surface receptors and leads to the formation of reactive oxygen species (ROS), resulting in the signal transduction of cell survival and proliferation[8,9,10] One such DNA damage-independent pathway that has been extensively studied is the MAPK pathway that leads to survival of UV-irradiated cells[11]. Several papers on the microarray analysis of UV-B irradiated melanocytes, another cellular component of the epidermis, have been published[18,19,20] These studies were performed under the assumption of a physiological situation in which only UV-B and UV-A range of solar UVR reach the earth and UV-B cause the most typical sun-induced reaction such as sunburn and suntan. Despite the extremely low dose of UV-C, almost all the genes with significantly upregulated expression were found to be mitotic genes, which function in the spindle assembly checkpoint
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