Abstract Arsenic (As) is a semi-metal which causes health problems in human, and immune system has been documented as one of the main target of arsenic toxicity. Apoptosis has a crucial role in regulation of immune system, but it can also have an important role in As immune suppression. So, we decided to assess the comprehensive mechanism of As cytotoxic effect on lymphocytes isolated from human blood. We determine the direct effect of arsenic on human lymphocytes which have a key role in immune system functionality. To evaluate the mechanism of arsenic toxicity on human lymphocytes, we use accelerated cytotoxicity mechanisms screening (ACMS) technique. Lymphocytes were isolated from blood of healthy persons using Ficoll-paque PLUS standard method. Following treatment of human lymphocytes with 0.05-50 μM of arsenic for 12 h, cell viability was measured. For determination of mechanistic parameters, isolated human lymphocytes incubated with 1/2IC5012h (7.5 μM), IC5012h (15 μM) and 2IC5012h (30 μM) for 2, 4 and 6 h. The results of this study demonstrate arsenic-associated apoptosis in human lymphocytes is mainly through enhancement of intracellular calcium which causes oxidative stress and following adverse effect on lymphocytes organelles (like mitochondria and lysosome). Involvement of cellular proteolysis, activation of caspase-3, lipid peroxidation and stimulation of cytokines (IL2, INF-gamma and TNF-alpha) production were also associated with arsenic induced lymphocyte toxicity.

中文翻译：

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砷对分离的人淋巴细胞的毒性：细胞因子和细胞内钙离子增强在砷诱导的细胞死亡中的关键作用

摘要 砷（As）是一种对人体造成健康问题的半金属，免疫系统已被证明是砷中毒的主要靶点之一。细胞凋亡在免疫系统的调节中起关键作用，但在As免疫抑制中也起重要作用。因此，我们决定评估 As 对从人血中分离的淋巴细胞的细胞毒性作用的综合机制。我们确定了砷对在免疫系统功能中起关键作用的人类淋巴细胞的直接影响。为了评估砷对人淋巴细胞的毒性机制，我们使用加速细胞毒性机制筛选 (ACMS) 技术。使用Ficoll-paque PLUS标准方法从健康人的血液中分离淋巴细胞。用 0.05-50 μM 的砷处理人淋巴细胞 12 小时后，测量细胞活力。为了确定机械参数，将分离的人淋巴细胞与 1/2IC5012h (7.5 μM)、IC5012h (15 μM) 和 2IC5012h (30 μM) 孵育 2、4 和 6 小时。这项研究的结果表明，人淋巴细胞中砷相关的细胞凋亡主要是通过细胞内钙的增加引起氧化应激和对淋巴细胞细胞器（如线粒体和溶酶体）的不利影响。参与细胞蛋白水解、caspase-3 激活、脂质过氧化和细胞因子（IL2、INF-γ 和 TNF-α）产生的刺激也与砷诱导的淋巴细胞毒性有关。这项研究的结果表明，人淋巴细胞中砷相关的细胞凋亡主要是通过细胞内钙的增强引起氧化应激和对淋巴细胞细胞器（如线粒体和溶酶体）的不利影响。参与细胞蛋白水解、caspase-3 激活、脂质过氧化和细胞因子（IL2、INF-γ 和 TNF-α）产生的刺激也与砷诱导的淋巴细胞毒性有关。这项研究的结果表明，人淋巴细胞中砷相关的细胞凋亡主要是通过细胞内钙的增加引起氧化应激和对淋巴细胞细胞器（如线粒体和溶酶体）的不利影响。参与细胞蛋白水解、caspase-3 激活、脂质过氧化和细胞因子（IL2、INF-γ 和 TNF-α）产生的刺激也与砷诱导的淋巴细胞毒性有关。