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卤代乙酸(HAAs)对……亚致死毒性的靶向代谢组学评估

Targeted Metabolomic Assessment of the Sub-Lethal Toxicity of Halogenated Acetic Acids (HAAs) to .

作者信息

Labine Lisa M, Simpson Myrna J

机构信息

Department of Chemistry, University of Toronto, 80 St. George St., Toronto, ON M5S 3H6, Canada.

Environmental NMR Centre and Department of Physical and Environmental Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada.

出版信息

Metabolites. 2021 Feb 10;11(2):100. doi: 10.3390/metabo11020100.

Abstract

Halogenated acetic acids (HAAs) are amongst the most frequently detected disinfection by-products in aquatic environments. Despite this, little is known about their toxicity, especially at the molecular level. The model organism , which is an indicator species for freshwater ecosystems, was exposed to sub-lethal concentrations of dichloroacetic acid (DCAA), trichloroacetic acid (TCAA) and dibromoacetic acid (DBAA) for 48 h. Polar metabolites extracted from were analyzed using liquid chromatography hyphened to a triple quadrupole mass spectrometer (LC-MS/MS). Multivariate analyses identified shifts in the metabolic profile with exposure and pathway analysis was used to identify which metabolites and associated pathways were disrupted. Exposure to all three HAAs led to significant downregulation in the nucleosides: adenosine, guanosine and inosine. Pathway analyses identified perturbations in the citric acid cycle and the purine metabolism pathways. Interestingly, chlorinated and brominated acetic acids demonstrated similar modes of action after sub-lethal acute exposure, suggesting that HAAs cause a contaminant class-based response which is independent of the type or number of halogens. As such, the identified metabolites that responded to acute HAA exposure may serve as suitable bioindicators for freshwater monitoring programs.

摘要

卤代乙酸(HAAs)是水环境中最常检测到的消毒副产物之一。尽管如此,人们对其毒性知之甚少,尤其是在分子水平上。作为淡水生态系统指示物种的模式生物,暴露于亚致死浓度的二氯乙酸(DCAA)、三氯乙酸(TCAA)和二溴乙酸(DBAA)中48小时。从该模式生物中提取的极性代谢物使用与三重四极杆质谱仪联用的液相色谱(LC-MS/MS)进行分析。多变量分析确定了暴露后代谢谱的变化,并使用通路分析来确定哪些代谢物和相关通路受到了干扰。暴露于所有三种HAAs均导致核苷(腺苷、鸟苷和肌苷)显著下调。通路分析确定了柠檬酸循环和嘌呤代谢通路中的扰动。有趣的是,氯化和溴化乙酸在亚致死急性暴露后表现出相似的作用模式,这表明HAAs会引发基于污染物类别的反应,而与卤素的类型或数量无关。因此,所鉴定出的对急性HAA暴露有反应的代谢物可能作为淡水监测计划的合适生物指示物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95a0/7916598/0f7e27cc3658/metabolites-11-00100-g001.jpg

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