Transcriptome Analysis in Mouse Skin After Exposure to Ultraviolet Radiation from a Canopy Sunbed
Exposure of skin to ultraviolet radiation (UV-R), in the form of both natural and artificial tanning, strongly increases the risk for developing skin cancer. On a molecular level, exposing cells and tissues to UV-R results in well-documented transcriptional changes. However, many of the previous investigations into these transcriptional responses did not adequately characterize the UV emissions or only assessed a limited number of doses or post-exposure times. As a result, our objectives were to provide a mechanistic study that describes the dose- and time-dependent changes in gene expression that drive adverse short-term (e.g. sunburn) and long-term actinic (e.g. skin cancer) possibly delineating response thresholds. In the current study, we examined transcriptomic expression data from mouse skin following exposure to five erythemally-weighted doses (0, 5, 10, 20, 40 mJ/cm2) of UV-R emitted from a UV-emitting tanning device, with six post-exposure durations of 0, 6, 24, 48, 72 and 96 hours (h).  Surprisingly, the lowest sub-erythemal dose of 5 mJ/cm2, produced 116 significant DEGs at 96 h post-exposure related to genes associated with structural changes associated with UV-R damage. The largest number of significant changes in gene expression were found at the 6 and 48 h post-exposure time points at the doses of 20 and 40 mJ/cm2. At the highest dose of 40 mJ/cm2, 13 differentially expressed genes of interest were commonly perturbed across all post-exposure time points relative to the time-matched control groups.  UV-R exposure induced pathways related to oxidative stress, P53 signaling, inflammation, biotransformation, skin barrier maintenance and innate immunity. The transcriptional data generated in this in vivo study provides mechanistic insight into the short-term and potential long-term health effects of exposure to UV-R tanning that may not be threshold dependent. Overall design: Mice were exposed to different doses of ultraviolet radiation (UVA96.4% / UVB3.6%) emitted from 8 (100Watt) UV fluorescent lamps from a tanning canopy, including sham-handled control. 5 spectral ultraviolet radiation doses (0 (sham-handled control), 5, 10, 20, or 40 mJ/cm2) were tested in quintuple (5 animals per dose = 25 samples) over 6 timepoints (0, 6, 24, 48, 72, 96 h = 150 samples in total, with a randomized design to avoid batch effects. Five samples were removed due to animal death before the final time point or low RNA yield