Effects of nitrogen-doped multi-walled carbon nanotubes compared to pristine multi-walled carbon nanotubes on human small airway epithelial cells

Toxicology. 2015 Jul 3:333:25-36. doi: 10.1016/j.tox.2015.03.008. Epub 2015 Mar 20.

Abstract

Nitrogen-doped multi-walled carbon nanotubes (ND-MWCNTs) are modified multi-walled carbon nanotubes (MWCNTs) with enhanced electrical properties that are used in a variety of applications, including fuel cells and sensors; however, the mode of toxic action of ND-MWCNT has yet to be fully elucidated. In the present study, we compared the interaction of ND-MWCNT or pristine MWCNT-7 with human small airway epithelial cells (SAEC) and evaluated their subsequent bioactive effects. Transmission electron microscopy, X-ray photoelectron spectroscopy, Raman spectroscopy, and X-ray diffraction suggested the presence of N-containing defects in the lattice of the nanotube. The ND-MWCNTs were determined to be 93.3% carbon, 3.8% oxygen, and 2.9% nitrogen. A dose-response cell proliferation assay showed that low doses of ND-MWCNT (1.2μg/ml) or MWCNT-7 (0.12μg/ml) increased cellular proliferation, while the highest dose of 120μg/ml of either material decreased proliferation. ND-MWCNT and MWCNT-7 appeared to interact with SAEC at 6h and were internalized by 24h. ROS were elevated at 6 and 24h in ND-MWCNT exposed cells, but only at 6h in MWCNT-7 exposed cells. Significant alterations to the cell cycle were observed in SAEC exposed to either 1.2μg/ml of ND-MWCNT or MWCNT-7 in a time and material-dependent manner, possibly suggesting potential damage or alterations to cell cycle machinery. Our results indicate that ND-MWCNT induce effects in SAEC over a time and dose-related manner which differ from MWCNT-7. Therefore, the physicochemical characteristics of the materials appear to alter their biological effects.

Keywords: Functionalized multi-walled carbon nanotubes; Multi-walled carbon nanotubes; Reactive oxygen species.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bronchioles / drug effects*
  • Bronchioles / metabolism
  • Bronchioles / ultrastructure
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cyclin-Dependent Kinase 4 / metabolism
  • Dose-Response Relationship, Drug
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Epithelial Cells / ultrastructure
  • Humans
  • Microscopy, Electron, Scanning
  • Microscopy, Electron, Transmission
  • Nanotubes, Carbon / toxicity*
  • Nitrogen / metabolism
  • Nitrogen / toxicity*
  • Phosphothreonine / metabolism
  • Phosphotyrosine / metabolism
  • Photoelectron Spectroscopy
  • Reactive Oxygen Species / metabolism
  • Risk Assessment
  • Spectrum Analysis, Raman
  • Time Factors
  • Toxicity Tests / methods
  • X-Ray Diffraction

Substances

  • Nanotubes, Carbon
  • Reactive Oxygen Species
  • Phosphothreonine
  • Phosphotyrosine
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4
  • Nitrogen