Skin is a major barrier against external insults and is exposed to combinations of chemical and/or physical toxic agents. Co-exposure to the carcinogenic benzo[a]pyrene (B[a]P) and solar UV radiation is highly relevant in human health, especially in occupational safety. In vitro studies have suggested that UVB enhances B[a]P genotoxicity by activating the AhR pathway and overexpressing the cytochrome P450 enzymes responsible for the conversion of B[a]P into DNA damaging metabolites. Our present work involved more realistic conditions, namely ex vivo human skin explants and simulated sunlight (SSL) as a UV source. We found that topically applied B[a]P strongly induced expression of cutaneous cytochrome P450 genes and formation of DNA adducts. However, gene induction was significantly reduced when B[a]P was combined with SSL. Consequently, formation of BPDE-adducts was also reduced when B[a]P was associated with SSL. Similar results were obtained with primary cultures of human keratinocytes. These results indicate that UV significantly impairs B[a]P metabolism, and decreases rather than increases immediate toxicity. However, it cannot be ruled out that decreased metabolism leads to accumulation of B[a]P and delayed genotoxicity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.