Iron oxide nanoparticles (ION) are gaining importance as diagnostic and therapeutic tool of central nervous system diseases. Although oleic acid-coated ION (O-ION) have been described as stable and biocompatible, their potential neurotoxicity was scarcely evaluated in human nervous cells so far. The primary aim of this work was to assess the molecular and cellular effects of O-ION on human astrocytes (A172 cells) under different experimental conditions. An extensive set of cyto- and genotoxicity tests was carried out, including lactate dehydrogenase release assay, cell cycle alterations, and cell death production, as well as comet assay, γH2AX assay, and micronucleus (MN) test, considering also iron ion release capacity and alterations in DNA repair ability. Results showed a moderate cytotoxicity related to cell cycle arrest and cell death promotion, regardless of serum presence. O-ION induced genotoxic effects, namely primary DNA damage, as detected by the comet assay and H2AX phosphorylation, but A172 cells were able to repair this particular damage because no chromosome alterations were found (confirmed by MN test results). Accordingly, no effects on the DNA repair ability were observed. The presence of serum proteins did not influence O-ION toxicity. Iron ions released from the O-ION surface seemed not to be responsible for the cytotoxic and genotoxic effects observed. Environ. Mol. Mutagen. 2019. © 2019 Wiley Periodicals, Inc.

中文翻译：

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评价油酸涂层的氧化铁纳米粒子在人星形胶质细胞中诱导的细胞毒性和遗传毒性。

氧化铁纳米颗粒（ION）作为中枢神经系统疾病的诊断和治疗工具正变得越来越重要。尽管油酸包覆的ION（O-ION）被描述为稳定且具有生物相容性，但迄今为止，在人类神经细胞中几乎未评估其潜在的神经毒性。这项工作的主要目的是评估在不同实验条件下O-ION对人星形胶质细胞（A172细胞）的分子和细胞作用。进行了广泛的细胞和基因毒性测试，包括乳酸脱氢酶释放测定，细胞周期改变和细胞死亡产生，以及彗星测定，γH2AX测定和微核（MN）测试，同时还考虑了铁离子释放能力和DNA修复能力的改变。结果表明，与血清周期阻滞和细胞死亡促进有关的中等细胞毒性，与血清的存在无关。O-ION诱导了遗传毒性作用，即通过彗星测定法和H2AX磷酸化检测到了原发性DNA损伤，但是A172细胞能够修复这种特定损伤，因为未发现染色体改变（由MN测试结果证实）。因此，未观察到对DNA修复能力的影响。血清蛋白的存在不影响O-ION毒性。从O-ION表面释放的铁离子似乎与观察到的细胞毒性和遗传毒性无关。环境。大声笑 诱变剂。2019.©2019 Wiley Periodicals，Inc. 但是A172细胞能够修复这种特定的损伤，因为未发现染色体改变（由MN测试结果证实）。因此，未观察到对DNA修复能力的影响。血清蛋白的存在不影响O-ION毒性。从O-ION表面释放的铁离子似乎与观察到的细胞毒性和遗传毒性无关。环境。大声笑 诱变剂。2019.©2019 Wiley Periodicals，Inc. 但是A172细胞能够修复这种特定的损伤，因为未发现染色体改变（由MN测试结果证实）。因此，未观察到对DNA修复能力的影响。血清蛋白的存在不影响O-ION毒性。从O-ION表面释放的铁离子似乎与观察到的细胞毒性和遗传毒性无关。环境。大声笑 诱变剂。2019.©2019 Wiley Periodicals，Inc.