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Metabolism and cytotoxicity of diphenylarsinic acid, a degradation product of sea-dumped chemical warfare agents, in a rainbow trout liver cell line RTL-W1
Aquatic Toxicology ( IF 4.5 ) Pub Date : 2021-10-12 , DOI: 10.1016/j.aquatox.2021.105993
Hanna Niemikoski 1 , Kari K Lehtonen 2 , Aino Ahvo 2 , Ilse Heiskanen 3 , Paula Vanninen 4
Affiliation  

Recent studies have found primary degradation products of phenylarsenic chemical warfare agents (CWAs) accumulating in fish tissues, while the potential effects of these dumped phenylarsenic CWAs, such as Clark I and II, in the Baltic Sea biota are poorly understood. In this study, the metabolism and cytotoxicity of diphenylarsinic acid (DPA), a primary degradation product of phenylarsenic CWA, was studied by incubating rainbow trout cell line RTL-W1 cells in media with 100 mg/L DPA. Previously undescribed metabolites were identified by ultra-high performance liquid chromatography–high resolution mass spectrometry (UPHLCsingle bondHRMS). Moreover, the cytotoxicity of diphenylarsine glutathione conjugate (DPA-SG), the major metabolite of DPA, was studied. Cytotoxicity of the compounds was evaluated using the Neutral Red retention test (NRR), showing an IC50 value of 278 mg/L for DPA and 1.30 mg/L for DPA-SG, indicating that the glutathione (GSH) conjugate of DPA is more than two orders of magnitude toxic than DPA itself, suggesting that toxic properties of DPA are increased after conjugation with intracellular GSH leading enhanced toxicity after uptake. Results gained in this study give more detailed information for elucidating biological effects of dumped chemical munitions in marine environment. Moreover, the results help in assessing the environmental and health risks posed by marine munition continued presence and deterioration in the sea bottom.



中文翻译:

在虹鳟鱼肝细胞系 RTL-W1 中二苯胂酸的代谢和细胞毒性,海洋倾倒化学战剂的降解产物

最近的研究发现苯砷化学战剂 (CWAs) 的初级降解产物在鱼类组织中积累,而这些倾倒的苯砷化学战剂 (CWAs) 的潜在影响,如克拉克 I 和 II,对波罗的海生物群的潜在影响知之甚少。在本研究中,通过在含有 100 mg/L DPA 的培养基中培养虹鳟鱼细胞系 RTL-W1 细胞,研究了苯砷 CWA 的主要降解产物二苯胂酸 (DPA) 的代谢和细胞毒性。以前未描述的代谢物通过超高效液相色谱-高分辨质谱 (UPHLC单键人力资源管理系统)。此外,研究了 DPA 的主要代谢物二苯基胂谷胱甘肽结合物 (DPA-SG) 的细胞毒性。使用中性红保留试验 (NRR) 评估化合物的细胞毒性,显示 IC 50DPA 的值为 278 mg/L,DPA-SG 的值为 1.30 mg/L,表明 DPA 的谷胱甘肽 (GSH) 偶联物​​的毒性比 DPA 本身高两个数量级以上,表明偶联后 DPA 的毒性增加细胞内 GSH 在摄取后导致毒性增强。本研究中获得的结果为阐明倾弃的化学弹药在海洋环境中的生物效应提供了更详细的信息。此外,这些结果有助于评估海洋弹药在海底持续存在和恶化所带来的环境和健康风险。

更新日期:2021-10-20
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