Synergistic enhancement of H2O2 production in human epidermoid carcinoma cells by Benzo[a]pyrene and ultraviolet A radiation&star;<FN ID="FN2"><NO>&star;</NO>This research was supported by a Grant from the National Institute of Environmental Health Sciences (ES09843) and by a Dermatology Foundation Grant awarded to Huachen Wei.</FN>

Benzo[a]pyrene (BaP) is an ubiquitous environmental pollutant with potential carcinogenecity. It was shown that BaP, upon irradiation by UV A, enhanced the formation of 8-hydroxy-2′-deoxyguanosine in purified DNA and in cultured cells. The purpose of this present study was to determine whether BaP and UV radiation synergistically generate reactive oxygen species (ROS) that consequently result in the oxidation of DNA bases. In this study, the levels of H2O2 were measured as an indicator of ROS in A431 cells and primary human keratinocytes treated with BaP plus UV radiation. Production of H2O2 significantly increased from cells treated with BaP plus UVB or UVA, with the latter having a much greater effect. The responses of A431 cells and primary human keratinocytes to BaP and UVA irradiation were similar in generation of extracellular H2O2. Also, H2O2 production proportionally correlated with UVA and UVB dose, but was independent of time or BaP concentration. Treatment with catalase and general ROS scavengers significantly decreased H2O2 production from cells treated with BaP plus UVA, whereas scavengers of •O2−, •OH, and 1O2 had minimal effects. These results demonstrate that BaP synergistically enhances the production of H2O2 from cultured cells by UVA and, to a lesser extent, by UVB, supporting the hypothesis that interaction of BaP and UVA can generate ROS and further substantiate oxidative DNA damage that may lead to carcinogenesis. [Copyright &y& Elsevier]