title: Oxidative stress and cell-cycle change induced by coexposed PCB126 and benzo(a) pyrene to human hepatoma (HepG2) cells.
abstract: Benzo(a)pyrene (BaP) never exists in the environment as a single compound but always coexists with other chemicals. These chemicals may affect the toxicity of BaP. Our previous study confirmed that polychlorinated biphenyls (PCBs), which were recently found coexisting with BaP in various environmental media, dramatically enhanced the genotoxicity of BaP. But the known mechanisms associated with this phenomenon are limited. Because BaP's genotoxicity is highly associated with its ability to induce the oxidative stress, we propose that the coexistence of PCBs may enhance BaP's genotoxicity by affecting BaP-induced oxidative stress. In this study, the HepG2 cells were treated with either BaP (50 μM), 3,3',4,4',5-pentachlorobiphenyl (PCB126) (0.01, 0.1, 1, and 10 nM), or pretreated with PCB126 followed by a coexposure to BaP and PCB126. We found that the exposure to BaP alone effectively increased the level of reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), and the percentage of cells in G0/G1 phase, but decreased the percentage of S-phase cells. Compared to BaP alone, coexposure to both BaP and PCB126 effectively enhanced the levels of ROS and MDA as well as the percentage of cells in S phase, but decreased the levels of GSH and percentage of cells in G0/G1 phase. Our findings suggest that increasing oxidative stress and impairing the normal cell-cycle control may be mechanisms by which PCB126 enhances the genotoxity of BaP exposure.
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Li
authors.forename: Xiao-Nuan
authors.initials: XN
authors.lastname: Li
authors.forename: Xue-Min
authors.initials: XM
authors.lastname: Chen
authors.forename: Ai-Lin
authors.initials: AL
authors.lastname: Liu
authors.forename: Wen-Qing
authors.initials: WQ
authors.lastname: Lu
mesh_terms: D001564:Benzo(a)pyrene / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D004249:DNA Damage; D004785:Environmental Pollutants / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D004785:Environmental Pollutants; D017382:Reactive Oxygen Species; D001564:Benzo(a)pyrene; D011078:Polychlorinated Biphenyls; D005978:Glutathione; C023035:3,4,5,3',4'-pentachlorobiphenyl