Moe Birget, Peng Hanyong, Lu Xiufen, Chen Baowei, Chen Lydia W L, Gabos Stephan, Li Xing-Fang, Le X Chris
Division of Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2G3, Canada; Alberta Centre for Toxicology, Department of Physiology and Pharmacology, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
Division of Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2G3, Canada.
J Environ Sci (China). 2016 Nov;49:113-124. doi: 10.1016/j.jes.2016.10.004. Epub 2016 Oct 24.
The occurrence of a large number of diverse arsenic species in the environment and in biological systems makes it important to compare their relative toxicity. The toxicity of arsenic species has been examined in various cell lines using different assays, making comparison difficult. We report real-time cell sensing of two human cell lines to examine the cytotoxicity of fourteen arsenic species: arsenite (As), monomethylarsonous acid (MMA) originating from the oxide and iodide forms, dimethylarsinous acid (DMA), dimethylarsinic glutathione (DMAG), phenylarsine oxide (PAO), arsenate (As), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), monomethyltrithioarsonate (MMTTA), dimethylmonothioarsinate (DMMTA), dimethyldithioarsinate (DMDTA), 3-nitro-4-hydroxyphenylarsonic acid (Roxarsone, Rox), and 4-aminobenzenearsenic acid (p-arsanilic acid, p-ASA). Cellular responses were measured in real time for 72hr in human lung (A549) and bladder (T24) cells. IC values for the arsenicals were determined continuously over the exposure time, giving rise to IC histograms and unique cell response profiles. Arsenic accumulation and speciation were analyzed using inductively coupled plasma-mass spectrometry (ICP-MS). On the basis of the 24-hr IC values, the relative cytotoxicity of the tested arsenicals was in the following decreasing order: PAO≫MMA≥DMA≥DMAG≈DMMTA≥As≫MMTTA>As>DMDTA>DMA>MMA≥Rox≥p-ASA. Stepwise shapes of cell response profiles for DMA, DMAG, and DMMTA coincided with the conversion of these arsenicals to the less toxic pentavalent DMA. Dynamic monitoring of real-time cellular responses to fourteen arsenicals provided useful information for comparison of their relative cytotoxicity.
环境和生物系统中存在大量多样的砷物种，因此比较它们的相对毒性很重要。已使用不同的检测方法在各种细胞系中检测了砷物种的毒性，这使得比较变得困难。我们报告了对两种人类细胞系进行实时细胞传感，以检测十四种砷物种的细胞毒性：亚砷酸盐（As）、源自氧化物和碘化物形式的一甲基亚砷酸（MMA）、二甲基亚砷酸（DMA）、二甲基砷谷胱甘肽（DMAG）、苯胂氧化物（PAO）、砷酸盐（As）、一甲基砷酸（MMA）、二甲基砷酸（DMA）、一甲基三硫代砷酸盐（MMTTA）、二甲基一硫代砷酸盐（DMMTA）、二甲基二硫代砷酸盐（DMDTA）、3-硝基-4-羟基苯胂酸（洛克沙胂，Rox）和4-氨基苯胂酸（对氨基苯胂酸，p-ASA）。在人肺（A549）和膀胱（T24）细胞中实时测量细胞反应72小时。在暴露时间内连续测定砷化合物的IC值，从而得到IC直方图和独特细胞反应谱。使用电感耦合等离子体质谱（ICP-MS）分析砷的积累和形态。根据24小时IC值，测试的砷化合物的相对细胞毒性按以下降序排列：PAO≫MMA≥DMA≥DMAG≈DMMTA≥As≫MMTTA>As>DMDTA>DMA>MMA≥Rox≥p-ASA。DMA、DMAG和DMMTA的细胞反应谱的逐步形状与这些砷化合物向毒性较小的五价DMA的转化相吻合。对十四种砷化合物的实时细胞反应进行动态监测，为比较它们的相对细胞毒性提供了有用信息。
