232 Characterization of the epigenetic profile of epidermis in response to co-exposure to ultraviolet radiations and Benzo[a]pyrene

Human skin is daily exposed to environmental stressors that can significantly impair skin homeostasis and trigger different disorders including aging and cancers. Ultraviolet radiations (UVR) and polycyclic aromatic hydrocarbons such as Benzo[a]pyrene (BaP) are two main pollutants that can harm the skin. UVR is a complete carcinogen while exposure to BaP is known to trigger pathologies such as immunotoxicity. Co-exposure to UVR and BaP increases skin tumor incidence compared to BaP- or UVR-exposure alone. However, few data are available to explain the biological processes that are altered following co-exposure of skin to BaP and UVR. To get insight into the epigenetic alterations triggered in epidermal cells in response to co-exposure, a comparative mass-spectrometry-based proteomic analysis was performed on skin explants following exposure to either no pollutant, UVR or BaP+UVR. The epidermis was separated, and epidermal proteins were extracted from different cellular fractions before an LC-MS analysis based on a label-free quantitative approach was done. Bioinformatic analyses using partial least squares discriminant analyses and differential expression using the EpiFactors database were used to highlight proteins involved in epigenetic processes that were differentially expressed following the co-exposure. Among all the proteins differentially expressed upon the co-exposure, we identified 12 proteins playing a role in epigenetic functions. 7 of these were in the cytosolic fraction (BRE, CTPB1, CUL2A, DDB1, HMGN5, SRSF1, SRSF3), 4 in the membrane fraction (HMGB1, PRKDC, SFPQ, UBE2N) and 1 in the nuclear fraction (SF3B1). A better understanding of these epigenetic alterations after co-exposure to UV and BaP is of special interest to devise topical treatments that potentially maintain skin homeostasis.