Mihalchik AL, Ding W, McLoughlin CE, et al. 2015. Effects of pristine and nitrogen-doped multiwalled carbon nanotubes (ND-MWCNT) on reactive oxygen species (ROS) and cell cycle progression. In: The Toxicologist (p. 267), abstract of work presented at the Society of Toxicology 54th Annual Meeting, San Diego, CA, March.
ND-MWCNT are modified MWCNT with enhanced electrical properties that are used in a variety of applications including fuel cells and sensors; however, the mode of action of toxicity of ND-MWCNT has yet to be elucidated. Recent in vivo data showed that ND-MWCNT induced inflammation and fibrosis in mouse lungs to a lesser extent compared to pristine MWCNT. In this study, we compared the interaction of ND-MWCNT or Mitsui 7 MWCNT (MWCNT-7) with human small airway epithelial cells (SAEC) and evaluated their subsequent bioactivities. NDMWCNT were characterized by transmission electron microscopy, X-ray photon spectroscopy, and Raman spectroscopy, which suggested the presence of defects in the nanotube lattice. The nanotubes were determined to be 93.3% carbon, 3.8% oxygen, and 2.9% nitrogen. A dose-response MTS assay showed that low doses up to 12 μg/mL of ND-MWCNT and MWCNT-7 increased cellular proliferation, while the highest dose of 120 μg/mL significantly decreased proliferation. NDMWCNT and MWCNT-7 appeared to be engulfed by SAEC at 6h and were fully internalized by 24h. ROS was 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 1.2 μg/mL of ND-MWCNT or MWCNT-7 in a time-dependent manner, as shown by a decreased percentage of cells in S phase and an increased percentage of cells in S and G2 phase, respectively, thus, suggesting potential damage or alterations to cell cycle machinery. Our results indicate that exposure to MWCNT-7 or ND-MWCNT induces effects in SAEC possibly through different mechanisms that are potentially related to physicochemical characteristics that may alter their toxicity.