a Dipartimento di Chimica, Biologia e Biotecnologie , Università degli Studi di Perugia , Perugia , Italy.
b Istituto Zooprofilattico Sperimentale del Piemonte , Torino , Italy.
J Toxicol Environ Health A. 2018;81(10):333-348. doi: 10.1080/15287394.2018.1442758. Epub 2018 Mar 2.
Arsenic (As) is a global contaminant of terrestrial and aquatic environments posing concern for environmental and human health. The effects of subacute concentrations of arsenic trioxide (As) and dimethylarsinic acid (DMA) were examined using Crandell Rees feline kidney (CRFK), human hepatocellular carcinoma (PLC/PRF/5), and epithelioma papulosum cyprini (EPC). Whole monolayer with suffering cells (confluence 100%, pyknosis and refractive cells; value scale = 2) led to identification of subacute As concentrations for the three cell lines. The selected As concentrations were 1.33 µM for CRFK and 33.37 µM for PLC/PRF/5 and EPC, at 48 hr time point. The selected DMA concentrations were 0.67 mM for PLC/PRF/5, 1.33 mM for CRFK, and 2.67 mM for EPC for 48 hr. Unlike the As test, the three cell lines did not exhibit marked susceptibility to DMA-mediated toxicity. Several oxidative stress biomarker levels, directly or indirectly associated with reactive oxygen species (ROS) elimination including superoxide dismutase, catalase, glutathione peroxidases, glutathione reductase, glutathione S-transferase, glyoxalase I, glyoxalase II, and total glutathione, were determined in the three cell lines at 24 and 48 hr. Antioxidant responses in metal-treated cells were significantly altered compared to controls, suggesting a perturbation of redox state. The weakening of antioxidant pathway in either healthy or tumoral cells was greater using As than DMA. Differences in level of several oxidative stress biomarkers suggest that the oxidative stress mechanism induced by As is distinctly different from DMA. Multifaceted mechanisms of action underlying ROS generation in tumor and nontumor cells versus As and DMA exposure are thus involved. Since As-mediated toxicity is quite complex, more data regarding both oxidant-enhancement and oxidant-lowering strategies may be useful to improve knowledge regarding the influence of As on human and animal cells.
砷（As）是一种全球性的陆地和水生环境污染物，对环境和人类健康构成了威胁。本研究使用猫肾细胞（CRFK）、人肝癌细胞（PLC/PRF/5）和鲤鱼上皮瘤细胞（EPC）研究了亚急性浓度的三氧化二砷（As）和二甲基砷酸（DMA）的影响。当整个单层细胞（细胞融合度为 100%，出现核固缩和细胞折光性；赋值范围=2）出现受损伤的细胞时，确定了三种细胞系的亚急性砷浓度。选择的 As 浓度为 48 小时时 CRFK 的 1.33µM 和 PLC/PRF/5 和 EPC 的 33.37µM。选择的 DMA 浓度为 PLC/PRF/5 的 0.67mM、CRFK 的 1.33mM 和 EPC 的 2.67mM，作用时间均为 48 小时。与 As 试验不同，三种细胞系对 DMA 介导的毒性没有明显的敏感性。在 24 和 48 小时，在三种细胞系中测定了几种与活性氧（ROS）消除直接或间接相关的氧化应激生物标志物水平，包括超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶、谷胱甘肽还原酶、谷胱甘肽 S-转移酶、乙二醛酶 I、乙二醛酶 II 和总谷胱甘肽。与对照相比，金属处理细胞中的抗氧化反应明显改变，表明氧化还原状态受到干扰。与 DMA 相比，在健康或肿瘤细胞中，抗氧化途径的减弱更为明显。几种氧化应激生物标志物的水平差异表明，As 诱导的氧化应激机制与 DMA 明显不同。因此，肿瘤和非肿瘤细胞中 ROS 生成的作用机制涉及多方面。由于 As 介导的毒性相当复杂，关于氧化剂增强和氧化剂降低策略的更多数据可能有助于提高人们对 As 对人类和动物细胞影响的认识。
