Xu Huan, McClain Shea, Medina Sebastian, Lauer Fredine T, Douillet Christelle, Liu Ke Jian, Hudson Laurie G, Stýblo Miroslav, Burchiel Scott W
The University of New Mexico College of Pharmacy, Department of Pharmaceutical Sciences, Albuquerque, NM 87131, United States.
Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, United States.
Toxicol Lett. 2016 Nov 16;262:55-61. doi: 10.1016/j.toxlet.2016.09.008. Epub 2016 Sep 19.
It is known in humans and mouse models, that drinking water exposures to arsenite (As) leads to immunotoxicity. Previously, our group showed that certain types of immune cells are extremely sensitive to arsenic induced genotoxicity. In order to see if cells from different immune organs have differential sensitivities to As, and if the sensitivities correlate with the intracellular concentrations of arsenic species, male C57BL/6J mice were dosed with 0, 100 and 500ppb Asvia drinking water for 30d. Oxidation State Specific Hydride Generation- Cryotrapping- Inductively Coupled Plasma- Mass Spectrometry (HG- CT- ICP- MS) was applied to analyze the intracellular arsenic species and concentrations in bone marrow, spleen and thymus cells isolated from the exposed mice. A dose-dependent increase in intracellular monomethylarsonous acid (MMA) was observed in both bone marrow and thymus cells, but not spleen cells. The total arsenic and MMA levels were correlated with an increase in DNA damage in bone marrow and thymus cells. An in vitro treatment of 5, 50 and 500nM As and MMA revealed that bone marrow cells are most sensitive to As treatment, and MMA is more genotoxic than As. These results suggest that the differential sensitivities of the three immune organs to As exposure are due to the different intracellular arsenic species and concentrations, and that MMA may play a critical role in immunotoxicity.
在人类和小鼠模型中已知，通过饮用水接触亚砷酸盐（As）会导致免疫毒性。此前，我们的研究小组表明，某些类型的免疫细胞对砷诱导的基因毒性极为敏感。为了探究来自不同免疫器官的细胞对砷的敏感性是否存在差异，以及这些敏感性是否与细胞内砷物种的浓度相关，将雄性C57BL/6J小鼠通过饮用水分别给予0、100和500 ppb的砷，持续30天。采用氧化态特异性氢化物发生 - 低温捕集 - 电感耦合等离子体质谱法（HG - CT - ICP - MS）分析从暴露小鼠分离的骨髓、脾脏和胸腺细胞中的细胞内砷物种和浓度。在骨髓和胸腺细胞中均观察到细胞内一甲基亚砷酸（MMA）呈剂量依赖性增加，但在脾脏细胞中未观察到。总砷和MMA水平与骨髓和胸腺细胞中DNA损伤的增加相关。对5、50和500 nM的砷和MMA进行体外处理表明，骨髓细胞对砷处理最为敏感，且MMA比砷具有更强的基因毒性。这些结果表明，三个免疫器官对砷暴露的敏感性差异是由于细胞内砷物种和浓度不同，并且MMA可能在免疫毒性中起关键作用。
