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研究鳕鱼肝中与有毒化学战剂相关的苯胂化含毒物的体外代谢。

Studying the metabolism of toxic chemical warfare agent-related phenylarsenic chemicals in vitro in cod liver.

机构信息

Finnish Institute for Verification of the Chemical Weapons Convention (VERIFIN), Department of Chemistry, University of Helsinki, P.O. Box 55, FI-00014 University of Helsinki, Finland.

Thünen-Institute of Fisheries Ecology, Herwigstraße 31, 27572, Bremerhaven, Germany.

出版信息

J Hazard Mater. 2020 Jun 5;391:122221. doi: 10.1016/j.jhazmat.2020.122221. Epub 2020 Feb 3.

DOI:10.1016/j.jhazmat.2020.122221
PMID:32045807
Abstract

Large quantities of chemical warfare agents (CWAs), such as phenylarsenic chemicals, were disposed by sea-dumping after World War II. Nowadays, the release of these toxic chemicals from munitions poses a potential threat to living organisms. This study investigates the fate of these chemicals in fish by exposing selected CWA-related phenylarsenic chemicals and their oxidation products to cod (Gadus morhua) liver S9 fraction in vitro. Clark I (DA), Adamsite (DM) and their corresponding oxidation products as well as triphenylarsine oxide (TPA[ox]) and phenylarsonic acid (PDCA[ox]) were used as chemicals in in vitro experiments. Glutathione (GSH) conjugates of DA, DM and PDCA-related chemicals were found to be the most dominant metabolites, and methylated metabolites were detected as well, suggesting that these compounds are metabolised in the presence of cod liver enzymes. TPA[ox] was the only compound tested that did not form a GSH conjugate or methylated metabolite, indicating a different biotransformation pathway for this compound. Furthermore, hydroxylated metabolites were detected for each tested chemical. Due to their reactive nature, GSH conjugates may be difficult to detect in fish samples from CWA dumpsites. In contrast, both methylated and hydroxylated metabolites of phenylarsenic chemicals are promising target chemicals for the detection of CWA-related contamination in fish.

摘要

大量的化学战剂(CWA),如苯胂化学物质,在第二次世界大战后被通过倾倒入海进行了处理。如今,这些有毒化学物质从弹药中释放出来对生物构成了潜在威胁。本研究通过体外将选定的与 CWA 相关的苯胂化学物质及其氧化产物暴露给鳕鱼(Gadus morhua)肝 S9 部分,来研究这些化学物质在鱼类中的命运。Clark I(DA)、Adamsite(DM)及其相应的氧化产物以及三苯胂氧化物(TPA[ox])和苯胂酸(PDCA[ox])被用作体外实验中的化学物质。发现 DA、DM 和 PDCA 相关化学物质的谷胱甘肽(GSH)缀合物是最主要的代谢物,并且也检测到了甲基化代谢物,这表明这些化合物在鳕鱼肝酶存在的情况下被代谢。测试的唯一一种未形成 GSH 缀合物或甲基化代谢物的化合物是 TPA[ox],这表明该化合物具有不同的生物转化途径。此外,还检测到每种测试化学物质的羟基化代谢物。由于它们的反应性,GSH 缀合物可能难以在 CWA 倾倒场的鱼类样本中检测到。相比之下,苯胂化学物质的甲基化和羟基化代谢物是检测鱼类中与 CWA 相关污染的有前途的目标化学物质。

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