Mechanistic Toxicity Evaluation of Uncoated and PEGylated Single-Walled Carbon Nanotubes in Neuronal PC12 Cells

National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, Arkansas 72079, USA.
ACS Nano (Impact Factor: 12.88). 08/2011; 5(9):7020-33. DOI: 10.1021/nn2016259
Source: PubMed


We investigated and compared the concentration-dependent cytotoxicity of single-walled carbon nanotubes (SWCNTs) and SWCNTs functionalized with polyethylene glycol (SWCNT-PEGs) in neuronal PC12 cells at the biochemical, cellular, and gene expressional levels. SWCNTs elicited cytotoxicity in a concentration-dependent manner, and SWCNT-PEGs exhibited less cytotoxic potency than uncoated SWCNTs. Reactive oxygen species (ROS) were generated in both a concentration- and surface coating-dependent manner after exposure to these nanomaterials, indicating different oxidative stress mechanisms. More specifically, gene expression analysis showed that the genes involved in oxidoreductases and antioxidant activity, nucleic acid or lipid metabolism, and mitochondria dysfunction were highly represented. Interestingly, alteration of the genes is also surface coating-dependent with a good correlation with the biochemical data. These findings suggest that surface functionalization of SWCNTs decreases ROS-mediated toxicological response in vitro.

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Available from: Susan Lantz-McPeak, Jun 27, 2014
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    • "Cellular ROS was determined using a probe of DCFH-DA, which could be hydrolyzed to the nonfluorescent dichlorofluorescein (DCFH) by cellular esterase and further oxidized to the fluorescent dichlorofluorescein (DCF) by cellular ROS. Figure 6a, b shows the generation of cellular ROS induced by different concentrations of CNTs within 30 min and 4 h. Higher CNT concentrations even induced lower ROS production, which was similar to the result reported by Zhang et al. (2011) When incubated with middle concentrations (1.0–2.0 mg/L of CNTs), bacterial cells even generated more ROS, in which case these concentrations showed milder toxicity for growth of strain LA-4 with biphenyl. In contrast, SWCNTs induced a milder production of cellular ROS than MWCNTs and SWCNT-COOHs did for both short and long contact time. "
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