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Study of Molecular Events Associated with Single Wall Carbon Nanotubes Mediated Cellular Cytotoxicity

˜The œFASEB journal(2012)

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摘要
Carbon nanotubes, due to their unique and outstanding properties, have generated extraordinary interest and expectations for industrial and biomedical applications. The increasing mass production of SWCNT requires their biocompatibility studies to prevent the possible health hazards among workers involved in the research, manufacturing of these materials and in the general public. Lung epithelial cell lines were used to investigate the mechanism underlying for apoptosis induced by single wall carbon nanotubes. Our results showed a significant amount of incorporation of dUTPs in the nucleus confirming the induction of apoptosis, which was also validated by DNA fragmentation assay. The activity of caspases‐3 and caspase‐8 increased in a dose and time dependent manner in parallel to the morphological apoptosis. The levels of cytochrome c, cellular ATP, Ap‐1 factor, p53, p21, bax, and bcl‐2 also changed reflecting the activation of the apoptosis pathway. Together, in this study we show that apoptosis in lung epithelial cells exposed to single wall carbon nanotubes occurred through the activation of caspase cascade, which in turn triggers nuclear transcription factor AP‐1 and the release of cytochrome c from the mitochondria into the cytosol where it binds the apoptotic protease activating factor resulting in cell death.
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