Exposure of human skin to benzo[a]pyrene: role of CYP1A1 and aryl hydrocarbon receptor in oxidative stress generation

Abstract

Exposure to benzo[a]pyrene (BaP) can induce inflammatory skin diseases and skin cancer, which are both associated to oxidative stress. BaP is known to bind with high specificity to the aryl hydrocarbon receptor (AhR), modifying the expression of CYP1A1, involved both in cancer and inflammation. While the current knowledge is based on murine skin and cell culture data, in this study human healthy skin has been treated with 5muM BaP in conditions simulating occupational and environmental exposure. AhR and CYP1A1 expression was evaluated by Western blotting, which revealed their presence even in control untreated skin; both enzyme and receptor increased more than twofold after exposure to BaP. AhR expression level was lower than CYP1A1 in basal conditions and following induction. Oxidative stress was evaluated in terms of MTT reduction, protein peroxidation and reactive oxygen species (ROS) formation. A significant increase in ROS and carbonyl compound production, as well as reduced tissue viability have been determined by BaP. The results of this experiment indicate that BaP, an AhR agonist, can significantly increase receptor and CYP1A1 expression and induce oxidative stress in human skin, confirming the involvement of this pathway in the pathogenesis of tissue damage due to polycyclic aromatic hydrocarbons.