Arsenic-induced mitochondrial instability leading to programmed cell death in the exposed individuals
Arsenic-induced mitochondrial instability leading to programmed cell death in the exposed individuals
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DOI：
10.1016/j.tox.2007.12.029
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发表时间：
2008-04-18
期刊：
影响因子：
4.5
通讯作者：
Giri, Ashok K.
中科院分区：
文献类型：
--
作者：
Banerjee, Nilanjana;Banerjee, Mayukh;Giri, Ashok K.
在印度西孟加拉邦，九个地区有超过 600 万人通过饮用水接触砷。它被认为是世界上最大的砷灾难。砷是一种有据可查的人类致癌物，在任何其他动物模型中都不会诱发癌症。有趣的是，在较低浓度下，砷已知可在体外诱导各种癌细胞系凋亡。我们通过膜联蛋白 V-FITC 染色研究了 30 名砷暴露皮肤病变个体的人外周血单核细胞 (PBMC) 细胞凋亡，并与 28 名未暴露个体进行比较。与未暴露的个体相比，有皮肤损伤的个体中凋亡细胞的百分比显着更高（p < 0.001）。在有皮肤损伤的暴露个体中，细胞内活性氧 (ROS) 水平升高，线粒体膜通透性增加，细胞色素 C 释放增加，导致下游 caspase 活性增加。通过 DNA 梯子形成和共聚焦显微镜证实了砷诱导的 DNA 损伤。我们还观察到，慢性砷暴露降低了 Bcl-2/Bax 比率，并导致 PBMC 细胞周期停滞在 G(0)/G(1) 期。所有这些观察结果表明线粒体介导的途径可能是砷诱导的细胞凋亡的原因。 (C) 2008 Elsevier Ireland Ltd. 保留所有权利。
In West Bengal, India, more than 6 million people in nine districts are exposed to arsenic through drinking water. It is regarded as the greatest arsenic calamity in the world. Arsenic is a well-documented human carcinogen, which does not induce cancer in any other animal model. Interestingly, at lower concentrations, arsenic is known to induce apoptosis in various cancer cell lines in vitro. We have studied apoptosis in human peripheral blood mononuclear cells (PBMC) of 30 arsenic exposed skin lesion individuals by annexin V-FITC staining and compared with 28 unexposed individuals. The percentage of apoptotic cells in individuals with skin lesions was significantly higher (p < 0.001) in comparison to unexposed individuals. In the exposed individuals with skin lesions, there were elevated levels of intracellular reactive oxygen species (ROS), mitochondrial membrane permeability and increased cytochrome c release, leading to increased downstream caspase activity. Arsenic-induced DNA damage was confirmed by DNA ladder formation and confocal microscopy. We also observed that chronic arsenic exposure reduced Bcl-2/Bax ratio and also resulted in cell cycle arrest of PBMC in G(0)/G(1) phase. All these observations indicate that mitochondria-mediated pathway may be responsible for arsenic-induced apoptosis. (C) 2008 Elsevier Ireland Ltd. All rights reserved.