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

IF 2.1 4区 医学 Q3 CHEMISTRY, MULTIDISCIPLINARY Drug and Chemical Toxicology Pub Date : 2025-01-21 DOI:10.1080/01480545.2025.2453580
Vesna Matovic, Biljana Ljujic, Marina Miletic Kovacevic, Olivera Milosevic-Djordjevic, Nevena Milivojevic, Sandra Nikolic, Marina Gazdic Jankovic
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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.

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聚苯乙烯纳米颗粒诱导no介导的DNA损伤触发间充质干细胞程序性细胞死亡。
日常接触大量聚苯乙烯纳米颗粒(psnp)可能对生物体造成有害影响,其机制尚不完全清楚。本研究旨在评价psnp(大小分别为200 nm和40 nm)对间充质干细胞(MSCs)的细胞毒性和基因毒性作用。为了估计纳米塑料的细胞摄取和保留,通过透射电子显微镜分析了psnp处理的细胞。以环境相关剂量(0.47 μl/ml和4.7 μl/ml)处理MSCs 24小时后,采用HE染色和Giemsa染色观察MSCs的形态学和活力。Annexin V - FITC/PI法用于定量psnp介导的细胞死亡。采用Comet试验评价psnp的遗传毒性。我们还评估了PSNPs在MSCs中引发自由基产生的能力。透射电镜证实了psnp的内吞作用。细胞体积减小,细胞核深染,边缘聚集,形成密集染色的凋亡小体,表明psnp处理的MSCs发生凋亡。数据显示,与未处理的细胞相比,两种浓度的PS颗粒均显著增加了早期凋亡细胞的死亡。此外,两种剂量的psnp均以剂量依赖的方式显著增加MSCs的遗传损伤指数。综上所述,PSNPs在MSCs中渗透、积累并诱导细胞毒性和基因毒性损伤。
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来源期刊
Drug and Chemical Toxicology
Drug and Chemical Toxicology 医学-毒理学
CiteScore
6.00
自引率
3.80%
发文量
99
审稿时长
3 months
期刊介绍: Drug and Chemical Toxicology publishes full-length research papers, review articles and short communications that encompass a broad spectrum of toxicological data surrounding risk assessment and harmful exposure. Manuscripts are considered according to their relevance to the journal. Topics include both descriptive and mechanics research that illustrates the risk assessment implications of exposure to toxic agents. Examples of suitable topics include toxicological studies, which are structural examinations on the effects of dose, metabolism, and statistical or mechanism-based approaches to risk assessment. New findings and methods, along with safety evaluations, are also acceptable. Special issues may be reserved to publish symposium summaries, reviews in toxicology, and overviews of the practical interpretation and application of toxicological data.
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