The toxicity of organoarsenic-based warfare agents: In vitro and in vivo studies
The toxicity of organoarsenic-based warfare agents: In vitro and in vivo studies
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DOI：
10.1007/bf00215800
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发表时间：
1996-02-01
影响因子：
4
通讯作者：
Norrgren, L
中科院分区：
文献类型：
--
作者：
Henriksson, J;Johannisson, A;Norrgren, L
使用体外和体内模型对四种含砷化学战剂（CWA）----亚当氏剂（工业用，10-氯-9-10-二氢苯胂）、克拉克1号（氯化二苯胂）、克拉克2号（氰化二苯胂）和路易氏剂（2-氯-乙烯基二氯胂）进行了毒理学评价。使用人白细胞在体外测试CWA，以评估其对细胞增殖和通过流式细胞术测定的细胞周期动力学的影响。CWA完全抑制细胞增殖的浓度范围为0.3 μ g/mL（Lewisite）至15 μ g/mL（Clark 1）。结果显示，当用CWA处理的样品与未处理的对照相比时，在无作用或作用浓度下，S期的不同阶段之间的细胞增殖没有差异。以As2O5为参比，完全抑制细胞增殖所需的砷浓度为1.7 mg/mL。较低的砷浓度，0.83 μ g/mL，表现出在S-期的不同部分的增殖率下降，S-早期和S-晚期分别具有最高和最低的比率。此外，未标记的S期细胞比例与砷浓度呈正相关，表明DNA合成停止。总之，检查CWAs发挥毒性更有效的砷，就细胞增殖。这可能表明，这些含砷化学武器的毒性只有在很小程度上可以解释其砷含量。由于它们相对良好的水溶性和容易降解为砷酸的能力，有机砷，例如，路易氏体对环境的威胁小于有机砷，有机砷是微溶的和化学持久性的，如亚当。四个CWA也在体内进行了测试，在饮食暴露研究，使用少年三棘鱼（Gasterosteus aculeatus L.）作为试验生物体，测量EROD活性并研究肝脏形态。体内研究的结果表明，影响很小，表明在测试剂量水平（1和100纳克/毫升）下10周的饮食接触对三棘鱼幼鱼的影响很小。
The four arsenic-containing chemical warfare agents (CWA) Adamsite (technical, 10-chloro-9-10-dihydrophenarsazine), Clark 1 (Diphenyl arsine chloride), Clark 2 (Diphenyl arsine cyanide), and Lewisite (2-chloro-ethenyl dichloro arsine) were evaluated toxicologically using an in vitro and an in vivo model. The CWA were tested in vitro, using human leucocytes, in order to evaluate their effects on cell proliferation and cell cycle kinetics assayed by flow cytometry. The concentration for total inhibition of cell proliferation for the CWAs ranged from 0.3 mu g/mL (Lewisite) to 15 mu g/mL (Clark 1). The results showed no differences in cell proliferation between the different stages of the S-phase either at no-effect or at effect concentrations when samples treated with the CWAs were compared with untreated controls. As2O5 was used as a reference, and the arsenic concentration required for total inhibition of the cell proliferation was 1.7 mg/mL. A lower arsenic concentration, 0.83 mu g/mL, showed a decreasing proliferation ratio in the different parts of the S-phase with S-early and S-late having the highest and lowest ratios, respectively. In addition, there was a positive correlation between the unlabeled S-phase cell ratio and the arsenic concentration, indicating cessation of DNA-synthesis. Conclusively, the examined CWAs exerts a toxicity more potent than arsenic, with respect to cell proliferation. This might indicate that the toxicity of these arsenic-containing CWAs only to a minor extent can be explained by their arsenic content. Because of their relatively good water solubility and ability to easily degrade to arsenic acid, organo-arsenics, e.g., Lewisite, pose less of an environmental threat than organo-arsenics that are sparingly soluble and chemically persistent, like Adamsite. The four CWAs were also tested in vivo in a dietary exposure study, using juvenile three-spined stickleback (Gasterosteus aculeatus L.) as test organism, with measurement of EROD-activity and studies of liver morphology. The results from the in vivo study indicated small effects, suggesting that a 10-week period of dietary exposure at tested dose levels (1 and 100 ng/ml) affects juvenile three-spined stickleback only to a minor extent.