Genotoxic potential of copper oxide nanoparticles in human lung epithelial cells
Genotoxic potential of copper oxide nanoparticles in human lung epithelial cells
复制标题
DOI：
10.1016/j.bbrc.2010.04.156
复制
发表时间：
2010-05-28
影响因子：
3.1
通讯作者：
Alhadlaq, Hisham A.
中科院分区：
文献类型：
--
作者：
Ahamed, Maqusood;Siddiqui, Maqsood A.;Alhadlaq, Hisham A.
氧化铜纳米颗粒(CuO NPs)在各种领域的应用越来越广泛。最近的研究表明，氧化应激可能是CuO纳米颗粒对哺乳动物细胞毒性的原因。然而，关于CuO纳米颗粒暴露于人类细胞后的遗传毒性知之甚少。本研究旨在探讨纳米CuO通过P53途径诱导人肺上皮细胞(A549)的遗传毒性反应。此外，还对细胞毒性和氧化应激标志物进行了评估。结果表明，CuO纳米颗粒可降低细胞存活率，且降低程度呈剂量依赖性。CuO纳米颗粒还以剂量依赖的方式诱导氧化应激，表现为谷胱甘肽的耗竭和脂质过氧化、过氧化氢酶和超氧化物歧化酶的诱导。CuO纳米粒可诱导细胞损伤的一级生物标志物Hsp70的表达。此外，CuO NPs上调了细胞周期检查点蛋白P53和DNA损伤修复蛋白RAD51和MSH2的表达。这些结果表明，CuO纳米颗粒对A549细胞具有潜在的遗传毒性，这种毒性可能是通过氧化应激来实现的。我们的短期暴露研究高水平诱导CuO纳米颗粒的遗传毒性反应将需要进一步调查，以确定长期暴露是否可能存在使用CuO纳米颗粒的后果。(C)2010 Elsevier Inc.保留所有权利。
Copper oxide nanoparticles (CuO NPs) are increasingly used in various applications. Recent studies suggest that oxidative stress may be the cause of the cytotoxicity of CuO NPs in mammalian cells. However, little is known about the genotoxicity of CuO NPs following exposure to human cells. This study was undertaken to investigate CuO NPs induced genotoxic response through p53 pathway in human pulmonary epithelial cells (A549). In addition, cytotoxicity and oxidative stress markers were also assessed. Results showed that cell viability was reduced by CuO NPs and degree of reduction was dose dependent. CuO NPs were also found to induce oxidative stress in dose-dependent manner indicated by depletion of glutathione and induction of lipid peroxidation, catalase and superoxide dismutase. The expression of Hsp70, the first tier biomarker of cellular damage was induced by CuO NPs. Further, CuO NPs up-regulated the cell cycle checkpoint protein p53 and DNA damage repair proteins Rad51 and MSH2 expression. These results demonstrate that CuO NPs possess a genotoxic potential in A549 cells which may be mediated through oxidative stress. Our short-term exposure study of high level induction of genotoxic response of CuO NPs will need to be further investigated to determine whether long-term exposure consequences may exist for CuO NPs application. (C) 2010 Elsevier Inc. All rights reserved.