Dose-dependent genotoxicity of copper oxide nanoparticles stimulated by reactive oxygen species in human lung epithelial cells
Dose-dependent genotoxicity of copper oxide nanoparticles stimulated by reactive oxygen species in human lung epithelial cells
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DOI：
10.1177/0748233713511512
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发表时间：
2016-05-01
影响因子：
1.9
通讯作者：
Ahamed, Maqusood
中科院分区：
文献类型：
--
作者：
Akhtar, Mohammad Javed;Kumar, Sudhir;Ahamed, Maqusood
氧化铜纳米粒子（CuO NPs）由于其广泛的工业和商业应用而在纳米科学和纳米技术中引起了极大的兴趣。因此，需要彻底了解CuO纳米颗粒的毒性。本研究的目的是研究CuO纳米颗粒在人肺上皮细胞（A549）中诱导的细胞毒性、遗传毒性和氧化应激。通过溶剂热法合成CuO纳米颗粒，并且发现在透射电子显微镜（TEM）下测量的纳米颗粒的尺寸为约23 nm。3-（4，5-二甲基噻唑-2-基）-2，5-二苯基四唑溴化物（MTT）和乳酸脱氢酶（LDH）测定显示CuO NPs（5-15 μ g/ml）以剂量依赖性方式在A549细胞中发挥细胞毒性。彗星试验表明，由于暴露于CuO纳米颗粒，DNA损伤的浓度依赖性诱导。在15 μ g/ml的CuO NPs中彗星尾矩为27%，而在对照中为5%（p < 0.05）。流式细胞仪数据显示CuO NPs在A549细胞中诱导微核（MN）呈剂量依赖性。在15 μ g/ml的CuO NPs中，MN的频率为25/10（3）个细胞，而对照为2/10（3）个细胞。CuO纳米颗粒也被发现以浓度依赖性的方式诱导氧化应激，这是通过诱导活性氧（ROS）和脂质过氧化沿着谷胱甘肽耗竭来指示的。此外，MN诱导和DNA损伤与ROS显著相关（ROS与Olive尾矩的R-2 = 0.937，ROS与MN的R-2 = 0.944）。总之，该研究表明CuO NPs在A549细胞中诱导遗传毒性，这可能是通过ROS产生和氧化应激介导的。
Copper oxide nanoparticles (CuO NPs) are of great interest in nanoscience and nanotechnology because of their broad industrial and commercial applications. Therefore, toxicity of CuO NPs needs to be thoroughly understood. The aim of this study was to investigate the cytotoxicity, genotoxicity, and oxidative stress induced by CuO NPs in human lung epithelial (A549) cells. CuO NPs were synthesized by solvothermal method and the size of NPs measured under transmission electron microscopy (TEM) was found to be around 23 nm. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) and lactate dehydrogenase (LDH) assays showed that CuO NPs (5-15 mu g/ml) exert cytotoxicity in A549 cells in a dose-dependent manner. Comet assay suggested concentration-dependent induction of DNA damage due to the exposure to CuO NPs. The comet tail moment was 27% at 15 mu g/ml of CuO NPs, whereas it was 5% in control (p < 0.05). The flow cytometry data revealed that CuO NPs induced micronuclei (MN) in A549 cells dose dependently. The frequency of MN was 25/10(3) cells at 15 mu g/ml of CuO NPs, whereas it was 2/10(3) cells for control. CuO NPs were also found to induce oxidative stress in a concentration-dependent manner, which was indicated by induction of reactive oxygen species (ROS) and lipid peroxidation along with glutathione depletion. Moreover, MN induction and DNA damage were significantly correlated with ROS (R-2 = 0.937 for ROS vs. olive tail moment, and R-2 = 0.944 for ROS vs. MN). Taken together, this study suggested that CuO NPs induce genotoxicity in A549 cells, which is likely to be mediated through ROS generation and oxidative stress.