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硫芥诱导的 DNA 加合物的研究进展:鉴定与检测。

Advances in sulfur mustard-induced DNA adducts: Characterization and detection.

机构信息

Department of Biology and Chemistry, College of Liberal Arts and Sciences, National University of Defense Technology, Changsha, 410073, PR China; State Key Laboratory of NBC Protection for Civilian, Beijing, 102205, PR China.

State Key Laboratory of NBC Protection for Civilian, Beijing, 102205, PR China.

出版信息

Toxicol Lett. 2021 Jun 15;344:46-57. doi: 10.1016/j.toxlet.2021.03.004. Epub 2021 Mar 8.

Abstract

Sulfur mustard (SM) is a blister chemical warfare agent with severe cytotoxicity and genotoxicity. It can extensively alkylate important macromolecules in organisms, such as proteins, DNA, and lipids, and produce a series of metabolites, among which the characteristic ones can be used as biomarkers. The exact toxicological mechanisms of SM remain unclear but mainly involve the DNA lesions induced by alkylation and oxidative stress caused by glutathione depletion. Various methods have been used to analyze DNA damage caused by SM. Among these methods, liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology stands out and makes it possible to observe damage in view of biomarkers induced by SM. Sample preparation is critical for detection by LC-MS/MS and mainly includes DNA isolation, adduct hydrolysis, and adduct purification. Moreover, optimization of chromatographic conditions, selection of MS transitions, and quantitative strategies are also essential. SM-DNA adducts are generally considered to be N-HETEG, O-HETEG, N-BisG, and N-HETEA. This article proposes some other possibilities of SM-DNA adducts for the identification of SM genotoxicity.

摘要

芥子气(SM)是一种水疱性化学战剂,具有严重的细胞毒性和遗传毒性。它可以广泛地烷化生物体内的重要大分子,如蛋白质、DNA 和脂质,并产生一系列代谢物,其中特征性代谢物可作为生物标志物。SM 的确切毒理学机制仍不清楚,但主要涉及烷基化引起的 DNA 损伤和谷胱甘肽耗竭引起的氧化应激。已经使用了各种方法来分析 SM 引起的 DNA 损伤。在这些方法中,液相色谱-串联质谱(LC-MS/MS)技术脱颖而出,使得观察 SM 诱导的生物标志物引起的损伤成为可能。LC-MS/MS 检测的样品制备至关重要,主要包括 DNA 分离、加合物水解和加合物纯化。此外,还需要优化色谱条件、选择 MS 转换和定量策略。SM-DNA 加合物通常被认为是 N-HETEG、O-HETEG、N-BisG 和 N-HETEA。本文提出了其他一些 SM-DNA 加合物的可能性,以鉴定 SM 的遗传毒性。

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