Synergistic enhancement of H2O2 production in human epidermoid carcinoma cells by Benzo[a]pyrene and ultraviolet A radiation

• Published in: Toxicology and applied pharmacology 2003-04, Vol.188 (2), p.104-109
• Main Authors: SHYONG, Eileen Q, YUHUN LU, GOLDSTEIN, Amy, LEBWOHL, Mark, HUACHEN WEI
• Format: Article
• Language: English
• Subjects: Antioxidants - pharmacology; Benzo(a)pyrene - toxicity; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Carcinogens - toxicity; Carcinoma, Squamous Cell - metabolism; Chemical agents; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Humans; Hydrogen Peroxide - metabolism; Indicators and Reagents; Keratinocytes - drug effects; Keratinocytes - metabolism; Keratinocytes - radiation effects; Medical sciences; Reactive Oxygen Species - metabolism; Tumor Cells, Cultured; Tumors; Ultraviolet Rays
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/S0041-008X(03)00018-8

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 H(2)O(2) were measured as an indicator of ROS in A431 cells and primary human keratinocytes treated with BaP plus UV radiation. Production of H(2)O(2) 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 H(2)O(2). Also, H(2)O(2) 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 H(2)O(2) production from cells treated with BaP plus UVA, whereas scavengers of *O2-, *OH, and (1)O(2) had minimal effects. These results demonstrate that BaP synergistically enhances the production of H(2)O(2) 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.