Genotoxic and mutagenic properties of Ni and NiO nanoparticles investigated by comet assay, γ-H2AX staining, Hprt mutation assay and ToxTracker reporter cell lines.

Genotoxic and mutagenic properties of Ni and NiO nanoparticles investigated by comet assay, γ-H2AX staining, Hprt mutation assay and ToxTracker reporter cell lines.
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DOI:
10.1002/em.22163
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发表时间:
2018-04
影响因子:
2.8
通讯作者:
Karlsson HL
Karlsson HL
中科院分区:
环境科学与生态学3区
文献类型:
--
作者:
Åkerlund E;Cappellini F;Di Bucchianico S;Islam S;Skoglund S;Derr R;Odnevall Wallinder I;Hendriks G;Karlsson HL

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镍(Ni)化合物被列为人类致癌物,但其潜在机制仍然知之甚少。此外,与Ni的纳米颗粒(NPs)相关的影响尚未完全阐明。本研究的目的是研究镍和NiO纳米颗粒的遗传毒性和致突变性,并比较从氯化镍可溶性镍的效果。我们采用了不同的模型,即,暴露于(1)人支气管上皮细胞(HBEC),然后进行DNA链断裂分析(彗星试验和γ-H2 AX染色);(2)6种不同的小鼠胚胎干(mES)报告细胞系(ToxTracker),构建这些细胞系以在诱导与(基因)毒性和癌症相关的各种途径时显示荧光;和(3)mES细胞,然后进行致突变性试验(Hprt试验)。结果显示NiO NP的DNA链断裂(彗星测定)增加,并且在较高剂量下Ni NP也增加,而对于来自NiCl 2的Ni离子/络合物没有观察到影响。通过使用报告细胞系,观察到氧化应激是主要的毒性机制,并且对于所有三种含镍材料,在细胞毒性剂量下发生蛋白质解折叠。NP暴露后,在HBEC细胞中也检测到氧化应激。这些材料均未诱导与直接DNA损伤和停滞复制叉相关的报告基因。对于NiO,观察到Hprt突变的小但统计学显著的增加,但仅在一个剂量下。我们的结论是,镍和NiO纳米粒子显示更明显的(基因)毒性作用相比,镍离子/复合物,表明更严重的健康问题。Environ.摩尔变异体59:211-222,2018.© 2017 The Authors Environmental and Molecular Mutagenesis出版由Wiley Periodicals,Inc.关于环境诱变剂协会
Nickel (Ni) compounds are classified as carcinogenic to humans but the underlying mechanisms are still poorly understood. Furthermore, effects related to nanoparticles (NPs) of Ni have not been fully elucidated. The aim of this study was to investigate genotoxicity and mutagenicity of Ni and NiO NPs and compare the effect to soluble Ni from NiCl2. We employed different models; i.e., exposure of (1) human bronchial epithelial cells (HBEC) followed by DNA strand break analysis (comet assay and γ‐H2AX staining); (2) six different mouse embryonic stem (mES) reporter cell lines (ToxTracker) that are constructed to exhibit fluorescence upon the induction of various pathways of relevance for (geno)toxicity and cancer; and (3) mES cells followed by mutagenicity testing (Hprt assay). The results showed increased DNA strand breaks (comet assay) for the NiO NPs and at higher doses also for the Ni NPs whereas no effects were observed for Ni ions/complexes from NiCl2. By employing the reporter cell lines, oxidative stress was observed as the main toxic mechanism and protein unfolding occurred at cytotoxic doses for all three Ni‐containing materials. Oxidative stress was also detected in the HBEC cells following NP‐exposure. None of these materials induced the reporter related to direct DNA damage and stalled replication forks. A small but statistically significant increase in Hprt mutations was observed for NiO but only at one dose. We conclude that Ni and NiO NPs show more pronounced (geno)toxic effects compared to Ni ions/complexes, indicating more serious health concerns. Environ. Mol. Mutagen. 59:211–222, 2018. © 2017 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society
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