title: The combined effects of BDE47 and BaP on oxidatively generated DNA damage in L02 cells and the possible molecular mechanism.
abstract: Polybrominated diphenyl ethers (PBDEs) and polycyclic aromatic hydrocarbons (PAHs) coexist widely in the environment and have generated adverse effects on the environment and human health. The purpose of this study was to investigate the combined toxic effects of these chemicals and the related mechanism. L02 cells were exposed to BDE47 (5, 10μmol/L) or/and BaP (50μmol/L) in different administration order. The cell growth and survival, DNA strand breaks, oxidative stress index (ROS, SOD, GSH, and MDA), LDH release and the expression level of CYP1 family members were measured. The result showed that BDE47 or/and BaP had no effect on the cell growth and survival under the present conditions. However, compared with the groups treated with BDE47 or BaP alone, the combined-treated groups induced significantly elevated DNA strand breaks, ROS production, and MDA level. Especially, pretreatment with BDE47 followed by BaP led to the strongest effects. Addition of the antioxidant N-acetyl-l-cysteine (NAC) markedly reduced the ROS level and partly suppressed the DNA strand breaks induced by BDE47 or/and BaP. Meanwhile, the combined treatment groups also markedly increased the SOD activity, GSH content, and LDH release level compared with the control group. The real-time PCR results showed that BaP could significantly induce the expression of CYP1A1 and CYP1B1, however, the pre-treatment with BDE47 appeared to attenuate the BaP-induced CYP1 expression. All of above findings indicated that BDE47 and BaP had a synergistic effect on oxidatively generated DNA damage in L02 cells via regulation on the oxidative stress response and the expression of CYP1 metabolism enzymes.
authors.affiliation: Institute of Environmental Pollution and Health, Shanghai University, Shanghai 200444, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: An
authors.forename: Lingling
authors.initials: L
authors.lastname: Yin
authors.forename: Yu
authors.initials: Y
authors.lastname: Shang
authors.forename: Yufang
authors.initials: Y
authors.lastname: Zhong
authors.forename: Xinyu
authors.initials: X
authors.lastname: Zhang
authors.forename: Minghong
authors.initials: M
authors.lastname: Wu
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Yu
authors.forename: Guoying
authors.initials: G
authors.lastname: Sheng
authors.forename: Jiamo
authors.initials: J
authors.lastname: Fu
authors.forename: Yuecheng
authors.initials: Y
authors.lastname: Huang
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000633:toxicity*; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1; D004249:DNA Damage; D055768:Halogenated Diphenyl Ethers / Q000008:administration & dosage / Q000633:toxicity*; D006801:Humans; D006836:Hydro-Lyases / Q000378:metabolism; D009153:Mutagens / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D055768:Halogenated Diphenyl Ethers; D009153:Mutagens; D001564:Benzo(a)pyrene; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D006836:Hydro-Lyases; C045581:lactate dehydratase