Sodium arsenite induces ROS generation, DNA oxidative damage, HO-1 and c-Myc proteins, NF-κB activation and cell proliferation in human breast cancer MCF-7 cells
Sodium arsenite induces ROS generation, DNA oxidative damage, HO-1 and c-Myc proteins, NF-κB activation and cell proliferation in human breast cancer MCF-7 cells
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DOI：
10.1016/j.mrgentox.2008.09.021
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发表时间：
2009-03-31
影响因子：
1.9
通讯作者：
Cebrian, Mariano E.
中科院分区：
文献类型：
--
作者：
Ruiz-Ramos, Ruben;Lopez-Carrillo, Lizbeth;Cebrian, Mariano E.
流行病学证据表明，饮用水中砷 (As) 的暴露与人类皮肤癌、膀胱癌、肝癌、肾癌和肺癌发病率的增加有关。亚砷酸钠模拟雌二醇的作用并诱导雌激素反应性乳腺癌细胞系 MCF-7 的细胞增殖。因此，我们的目的是通过研究ROS产生、c-Myc和HO-1蛋白水平、8-OHdG形成和NF-kappa B激活，进一步探讨亚砷酸钠诱导MCF-7上皮乳腺细胞增殖的能力及其一些潜在机制。低亚砷酸盐浓度（0.5-5μM）诱导ROS产生和线粒体膜ROS相关的去极化，表明线粒体在砷的氧化作用中发挥着重要作用。通过细胞核中 8-OHdG DNA 加合物的存在来测量 ROS 介导的 DNA 损伤、I kappa B 磷酸化、NF-kappa B 激活以及 c-Myc 和 HO-1 蛋白水平的增加，还观察到这些因素在亚砷酸盐诱导 MCF-7 细胞募集到细胞周期的 S 期和观察到的细胞增殖中发挥相关作用。总之，亚砷酸盐激活参与 MCF-7 细胞增殖的多种途径，表明亚砷酸盐暴露可能会给人类暴露人群带来患乳腺癌的风险，尽管迄今为止的大多数研究尚未表明这种类金属是该疾病病因学的辅助因子。 (C) 2008 Elsevier B.V. 保留所有权利
Epidemiological evidence has associated exposure to arsenic (As) in drinking water with an increased incidence of human cancers in the skin, bladder, liver, kidney and lung. Sodium arsenite mimics the effects of estradiol and induces cell proliferation in the estrogen responsive breast cancer cell line MCF-7. Therefore, our aim was to further explore the ability of sodium arsenite to induce MCF-7 epithelial breast cell proliferation and some of its underlying mechanisms by studying ROS production, c-Myc and HO-1 protein levels, 8-OHdG formation and NF-kappa B activation. Low arsenite concentrations (0.5-5 mu M) induced ROS production and ROS-related depolarization of the mitochondrial membrane suggesting that mitochondria played an important role in the oxidative effects of As. ROS-mediated DNA damage as measured by the presence of 8-OHdG DNA-adducts in their nuclei, I kappa B phosphorylation, NF-kappa B activation and increases in c-Myc and HO-1 protein levels were also observed, suggesting that these factors play a relevant role in the arsenite induced MCF-7 cell recruitment into the S-phase of the cell cycle and cell proliferation observed. In conclusion, arsenite activates several pathways involved in MCF-7 cell proliferation suggesting that arsenite exposure may pose a risk for breast cancer in human exposed populations notwithstanding that most studies to date have not yet implicated this metalloid as a cofactor in the etiology of this disease. (C) 2008 Elsevier B.V. All rights reserved