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多壁碳纳米管诱导人肺癌细胞系 A549 氧化应激和细胞凋亡。

Multi-walled carbon nanotubes induce oxidative stress and apoptosis in human lung cancer cell line-A549.

机构信息

Indian Institute of Toxicology Research, Lucknow, India.

出版信息

Nanotoxicology. 2011 Jun;5(2):195-207. doi: 10.3109/17435390.2010.503944. Epub 2010 Aug 31.

Abstract

Multi-walled carbon-nanotubes (MWCNTs)-induced apoptotic changes were studied in human lung epithelium cell line-A549. Non-cytotoxic doses of MWCNTs were identified using tetrazolium bromide salt (MTT) and lactate dehydrogenase (LDH) release assays. Cells were exposed to MWCNTs (0.5-100 μg/ml) for 6-72 h. Internalization and characterization of CNTs was performed by electron microscopy. Apoptotic changes were estimated by nuclear condensation, DNA laddering, and confirmed by expression of associated markers: p(53), p(21WAF1/CIP1), Bax, Bcl(2) and activated caspase-3. MWCNTs induced the production of reactive oxygen species and malondialdehyde along with significant decrease in the activity of catalase and glutathione. MWCNTs-induced ROS generation was found not to be associated with the mitochondrial activity. In general, the changes were significant at 10 and 50 μg/ml only. Results indicate the involvement of oxidative stress and apoptosis in A549 cells exposed to MWCNTs. Our studies provide insights of the mechanisms involved in MWCNTs-induced apoptosis at cellular level.

摘要

多壁碳纳米管 (MWCNTs) 诱导的人肺上皮细胞系 A549 细胞凋亡变化。使用噻唑蓝盐 (MTT) 和乳酸脱氢酶 (LDH) 释放试验确定非细胞毒性剂量的 MWCNTs。将细胞暴露于 MWCNTs (0.5-100μg/ml) 6-72 h。通过电子显微镜进行 CNTs 的内化和特性分析。通过核浓缩、DNA 梯状带和相关标志物的表达来评估凋亡变化:p(53)、p(21WAF1/CIP1)、Bax、Bcl(2)和活化的 caspase-3。MWCNTs 诱导活性氧物质和丙二醛的产生,同时过氧化氢酶和谷胱甘肽的活性显著下降。发现 MWCNTs 诱导的 ROS 生成与线粒体活性无关。一般来说,只有在 10 和 50μg/ml 时变化才显著。结果表明,暴露于 MWCNTs 的 A549 细胞中涉及氧化应激和细胞凋亡。我们的研究提供了在细胞水平上 MWCNTs 诱导细胞凋亡所涉及的机制的见解。

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