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暴露于硫芥二十多年后,伊朗老兵细胞对硫芥反应中的 DNA 损伤和修复蛋白。

DNA damage and repair proteins in cellular response to sulfur mustard in Iranian veterans more than two decades after exposure.

机构信息

Organization for the Prohibition of Chemical Weapons, The Hague, The Netherlands.

Medical Toxicology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Toxicol Lett. 2018 Sep 1;293:67-72. doi: 10.1016/j.toxlet.2017.12.001. Epub 2017 Dec 5.

Abstract

Delayed effects of sulfur mustard (SM) exposure on the levels of five important damage/repair proteins were investigated in 40 SM-exposed veterans of Iran-Iraq war and 35 unexposed controls. A major DNA damage biomarker protein - phosphorylated H2AX - along with four DNA repair proteins in cell response to the genome damage MRE11, NBS1, RAD51, and XPA were evaluated in blood lymphocytes from the veterans and controls using western blotting. Mean levels of XPA, MRE11, RAD51 and NBS1 were lower in SM-exposed patients and the decrease in NBS1 was significant. Even though the raised level of phosphor-H2AX in SM-poisoned group compared to the controls was not significant it was consistent with DNA damage findings confirming the severity of damage to the DNA after exposure to SM. There were correlations between the values of RAD51 and NBS1 proteins as well as XPA and MRE11 proteins. More than two decades after exposure to SM, there is still evidences of DNA damage as well as impaired repair mechanisms in cells of exposed individuals. Such disorders in cellular level may contribute to long term health problems of the SM veterans.

摘要

研究了 40 名伊朗-伊拉克战争中接触过硫芥的退伍军人和 35 名未接触过的对照者中,五种重要的损伤/修复蛋白水平受硫芥暴露的延迟影响。使用蛋白质印迹法从退伍军人和对照组的血液淋巴细胞中评估了主要的 DNA 损伤生物标志物蛋白 - 磷酸化 H2AX - 以及细胞对基因组损伤 MRE11、NBS1、RAD51 和 XPA 的四种 DNA 修复蛋白。暴露于 SM 的患者中 XPA、MRE11、RAD51 和 NBS1 的平均水平较低,NBS1 的减少具有显著性。尽管与对照组相比,SM 中毒组中磷酸化 H2AX 的水平升高不显著,但与 DNA 损伤发现一致,证实暴露于 SM 后 DNA 损伤的严重程度。RAD51 和 NBS1 蛋白以及 XPA 和 MRE11 蛋白之间存在相关性。暴露于 SM 二十多年后,暴露个体的细胞中仍然存在 DNA 损伤和修复机制受损的证据。这种细胞水平的紊乱可能导致 SM 退伍军人的长期健康问题。

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