The combined effects of BDE47 and BaP on oxidatively generated DNA damage in L02 cells and the possible molecular mechanism
The combined effects of BDE47 and BaP on oxidatively generated DNA damage in L02 cells and the possible molecular mechanism
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BDE47和BaP对L02细胞氧化DNA损伤的联合作用及其可能的分子机制
DOI：
10.1016/j.mrgentox.2011.02.002
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发表时间：
2011-04-03
影响因子：
1.9
通讯作者：
Huang, Yuecheng
中科院分区：
文献类型：
--
作者：
An, Jing;Yin, Lingling;Huang, Yuecheng
多溴联苯醚（PBDEs）和多环芳烃（PAHs）广泛共存于环境中，对环境和人类健康产生了严重的危害。本研究的目的是探讨这些化学品的联合毒性效应及其相关机制。将L02细胞暴露于BDE 47（5. 10 μ mol/L）或/和BaP（50 μ mol/L）不同给药顺序。细胞生长和存活、DNA链断裂、氧化应激指数（ROS、SOD）。GSH。MDA）。测定LDH释放和CYP 1家族成员的表达水平。结果表明，BDE 47和BaP对细胞的生长和存活无影响。然而，与单独使用BDE-47或BaP的处理组相比，联合处理组诱导的DNA链断裂显著增加。ROS产生和MDA水平。特别是，先用BDE 47预处理，再用BaP预处理，效果最强。添加抗氧化剂N-乙酰-L-半胱氨酸（NAC）显著降低了ROS水平，并部分抑制了BDE 47或/和BaP诱导的DNA链断裂。同时，联合用药组SOD活性、GSH含量和LDH释放水平均较对照组显著升高。实时荧光定量PCR结果显示，BaP可显著诱导CYP 1A 1和CYP 1B 1的表达，而BDE 47预处理可减弱BaP诱导的CYP 1表达。以上结果表明，BDE 47和BaP通过调节氧化应激反应和CYP 1代谢酶的表达，对L02细胞DNA氧化损伤具有协同作用。(C)2011 Elsevier B. V.保留所有权利。
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. 10 mu mol/L) or/and BaP (50 mu mol/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. (C) 2011 Elsevier B.V. All rights reserved.