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聚苯乙烯纳米颗粒诱导的一氧化氮介导的DNA损伤触发间充质干细胞的程序性细胞死亡。

NO-mediated DNA damage induced by polystyrene nanoparticles triggers program cell death in mesenchymal stem cells.

作者信息

Matovic Vesna, Ljujic Biljana, Miletic Kovacevic Marina, Milosevic-Djordjevic Olivera, Milivojevic Nevena, Nikolic Sandra, Jankovic Marina Gazdic

机构信息

Cardiology Clinic, University Clinical Center Kragujevac, Kragujevac, Serbia.

Department of Genetics, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.

出版信息

Drug Chem Toxicol. 2025 Jul;48(4):720-728. doi: 10.1080/01480545.2025.2453580. Epub 2025 Jan 21.

DOI:10.1080/01480545.2025.2453580
PMID:39837531
Abstract

Daily contact with considerable amounts of polystyrene nanoparticles (PSNPs) may cause harmful effects on the living organisms, through mechanisms that are not fully understood. The study aimed to evaluate the cytotoxic and genotoxic effects of PSNPs (size 200 nm and 40 nm) in mesenchymal stem cells (MSCs). In order to estimate cellular uptake and retention of nanoplastics, PSNP-treated cells have been analyzed by transmission electron microscopy. For assessing morphology and viability of MSCs after PSNP treatment at two environmentally relevant doses (0.47 and 4.7 μl/ml) for 24 hours, HE and Giemsa staining were performed. Annexin V‑FITC/PI assay was used to quantify PSNPs-mediated cell death. Genotoxicity of PSNPs was evaluated by Comet test. The capacity of PSNPs to trigger the production of free radicals in MSCs was also evaluated. TEM confirmed endocytosis of PSNPs. Decreased cell volume, nuclear hyperchromatism, edge aggregation, and formation of densely stained apoptotic bodies, indicated that PSNP-treated MSCs undergo apoptosis. The presented data showed that both concentration of PS particles significantly increased early apoptotic cell death in comparison to untreated cells. Moreover, both doses of PSNPs significantly increased the genetic damage index in MSCs in dose-dependent manner. In conclusion, PSNPs penetrate, accumulate and induce cytotoxic and genotoxic damage in MSCs.

摘要

每天接触大量聚苯乙烯纳米颗粒(PSNPs)可能会通过尚未完全了解的机制对生物体产生有害影响。本研究旨在评估PSNPs(尺寸为200纳米和40纳米)对间充质干细胞(MSCs)的细胞毒性和遗传毒性作用。为了估计纳米塑料的细胞摄取和保留情况,已通过透射电子显微镜对经PSNP处理的细胞进行了分析。为了评估在两个与环境相关的剂量(0.47和4.7微升/毫升)下PSNP处理24小时后MSCs的形态和活力,进行了苏木精-伊红(HE)和吉姆萨染色。采用膜联蛋白V-异硫氰酸荧光素/碘化丙啶(Annexin V-FITC/PI)检测法对PSNPs介导的细胞死亡进行定量。通过彗星试验评估PSNPs的遗传毒性。还评估了PSNPs在MSCs中引发自由基产生的能力。透射电子显微镜证实了PSNPs的内吞作用。细胞体积减小、核染色质增多、边缘聚集以及形成深色凋亡小体,表明经PSNP处理的MSCs发生了凋亡。所呈现的数据表明,与未处理的细胞相比,两种PS颗粒浓度均显著增加了早期凋亡细胞死亡。此外,两种剂量的PSNPs均以剂量依赖方式显著增加了MSCs中的遗传损伤指数。总之,PSNPs可穿透、积聚并在MSCs中诱导细胞毒性和遗传毒性损伤。

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