Banerjee Nilanjana, Banerjee Mayukh, Ganguly Sudipto, Bandyopadhyay Santu, Das Jayanta K, Bandyopadhay Apurba, Chatterjee Mitali, Giri Ashok K
Molecular and Human Genetics Division, Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, India.
Toxicology. 2008 Apr 18;246(2-3):101-11. doi: 10.1016/j.tox.2007.12.029. Epub 2008 Jan 12.
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 G0/G1 phase. All these observations indicate that mitochondria-mediated pathway may be responsible for arsenic-induced apoptosis.
在印度西孟加拉邦，九个地区的600多万人通过饮用水接触到砷。这被视为世界上最严重的砷灾难。砷是一种有充分文献记载的人类致癌物，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，已知砷能在体外诱导各种癌细胞系发生凋亡。我们通过膜联蛋白V-异硫氰酸荧光素（annexin V-FITC）染色研究了30名砷暴露皮肤病变个体的人外周血单个核细胞（PBMC）中的凋亡情况，并与28名未暴露个体进行了比较。与未暴露个体相比，有皮肤病变个体的凋亡细胞百分比显著更高（p<0.001）。在有皮肤病变的暴露个体中，细胞内活性氧（ROS）水平升高、线粒体膜通透性增加以及细胞色素c释放增加，导致下游半胱天冬酶活性增强。通过DNA梯带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比值，并导致PBMC细胞周期停滞在G0/G1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凋亡的原因。
