Center for Environmental Medicine, Asthma and Lung Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
Int J Environ Res Public Health. 2011 Jun;8(6):2090-108. doi: 10.3390/ijerph8062090. Epub 2011 Jun 8.
Chronic arsenic exposure results in higher risk of skin, lung, and bladder cancer, as well as cardiovascular disease and diabetes. The purpose of this study was to investigate the effects on expression of selected genes in the blood lymphocytes from 159 people exposed chronically to arsenic in their drinking water using a novel RT-PCR TaqMan low-density array (TLDA). We found that expression of tumor necrosis factor-α (TNF-α), which activates both inflammation and NF-κB-dependent survival pathways, was strongly associated with water and urinary arsenic levels. Expression of KCNA5, which encodes a potassium ion channel protein, was positively associated with water and toe nail arsenic levels. Expression of 2 and 11 genes were positively associated with nail and urinary arsenic, respectively. Because arsenic exposure has been reported to be associated with long QT intervals and vascular disease in humans, we also used this TLDA for analysis of gene expression in human cardiomyocytes exposed to arsenic in vitro. Expression of the ion-channel genes CACNA1, KCNH2, KCNQ1 and KCNE1 were down-regulated by 1-μM arsenic. Alteration of some common pathways, including those involved in oxidative stress, inflammatory signaling, and ion-channel function, may underlay the seemingly disparate array of arsenic-associated diseases, such as cancer, cardiovascular disease, and diabetes.
慢性砷暴露会增加皮肤癌、肺癌、膀胱癌、心血管疾病和糖尿病的风险。本研究旨在使用新型 RT-PCR TaqMan 低密度阵列 (TLDA) 研究 159 名长期饮用含砷水的人血液淋巴细胞中选定基因表达的变化。我们发现，肿瘤坏死因子-α (TNF-α) 的表达与水和尿液中的砷含量密切相关，TNF-α 既激活炎症反应，也激活 NF-κB 依赖性生存途径。编码钾离子通道蛋白的 KCNA5 的表达与水和趾甲中的砷含量呈正相关。有 2 个和 11 个基因的表达与趾甲和尿液中的砷含量分别呈正相关。由于砷暴露已被报道与人类的长 QT 间期和血管疾病有关，我们还使用该 TLDA 分析了体外暴露于砷的人心肌细胞中的基因表达。1μM 砷使离子通道基因 CACNA1、KCNH2、KCNQ1 和 KCNE1 的表达下调。一些常见途径的改变，包括涉及氧化应激、炎症信号和离子通道功能的途径的改变，可能是砷相关疾病（如癌症、心血管疾病和糖尿病）的基础。
