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四种典型纳米材料诱导的细胞毒性、氧化应激和遗传毒性的比较研究:粒径、形状和组成的作用

Comparative study of cytotoxicity, oxidative stress and genotoxicity induced by four typical nanomaterials: the role of particle size, shape and composition.

作者信息

Yang Hui, Liu Chao, Yang Danfeng, Zhang Huashan, Xi Zhuge

机构信息

Academy of Military Medical Sciences, Institute of Health & Environmental Medicine, Tianjin, China.

出版信息

J Appl Toxicol. 2009 Jan;29(1):69-78. doi: 10.1002/jat.1385.

DOI:10.1002/jat.1385
PMID:18756589
Abstract

Although the biological effects of some nanomaterials have already been assessed, information on toxicity and possible mechanisms of various particle types are insufficient. Moreover, the role of particle properties in the toxic reaction remains to be fully understood. In this paper, we aimed to explore the interrelationship between particle size, shape, chemical composition and toxicological effects of four typical nanomaterials with comparable properties: carbon black (CB), single wall carbon nanotube, silicon dioxide (SiO(2)) and zinc dioxide (ZnO) nanoparticles. We investigated the cytotoxicity, genotoxicity and oxidative effects of particles on primary mouse embryo fibroblast cells. As observed in the methyl thiazolyl tetrazolium (MTT) and water-soluble tetrazolium (WST) assays, ZnO induced much greater cytotoxicity than non-metal nanoparticles. This was significantly in accordance with intracellular oxidative stress levels measured by glutathione depletion, malondialdehyde production, superoxide dismutase inhibition as well as reactive oxygen species generation. The results indicated that oxidative stress may be a key route in inducing the cytotoxicity of nanoparticles. Compared with ZnO nanoparticles, carbon nanotubes were moderately cytotoxic but induced more DNA damage determined by the comet assay. CB and SiO(2) seemed to be less effective. The comparative analysis demonstrated that particle composition probably played a primary role in the cytotoxic effects of different nanoparticles. However, the potential genotoxicity might be mostly attributed to particle shape.

摘要

尽管一些纳米材料的生物学效应已得到评估,但关于各种颗粒类型的毒性及可能机制的信息仍不充分。此外,颗粒特性在毒性反应中的作用仍有待充分了解。在本文中,我们旨在探究四种具有可比性质的典型纳米材料——炭黑(CB)、单壁碳纳米管、二氧化硅(SiO₂)和氧化锌(ZnO)纳米颗粒的粒径、形状、化学成分与毒理学效应之间的相互关系。我们研究了这些颗粒对原代小鼠胚胎成纤维细胞的细胞毒性、遗传毒性和氧化作用。正如在噻唑蓝(MTT)和水溶性四氮唑盐(WST)检测中所观察到的,ZnO诱导的细胞毒性比非金属纳米颗粒大得多。这与通过谷胱甘肽消耗、丙二醛生成、超氧化物歧化酶抑制以及活性氧生成所测得的细胞内氧化应激水平显著一致。结果表明,氧化应激可能是诱导纳米颗粒细胞毒性的关键途径。与ZnO纳米颗粒相比,碳纳米管具有中等细胞毒性,但通过彗星试验测定其诱导的DNA损伤更多。CB和SiO₂似乎效果较差。对比分析表明,颗粒组成可能在不同纳米颗粒的细胞毒性作用中起主要作用。然而,潜在的遗传毒性可能主要归因于颗粒形状。

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