MWCNTs of different physicochemical properties cause similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs

Toxicol Appl Pharmacol. 2015 Apr 1;284(1):16-32. doi: 10.1016/j.taap.2014.12.011. Epub 2014 Dec 29.


Multi-walled carbon nanotubes (MWCNTs) are an inhomogeneous group of nanomaterials that vary in lengths, shapes and types of metal contamination, which makes hazard evaluation difficult. Here we present a toxicogenomic analysis of female C57BL/6 mouse lungs following a single intratracheal instillation of 0, 18, 54 or 162 μg/mouse of a small, curled (CNT(Small), 0.8 ± 0.1 μm in length) or large, thick MWCNT (CNT(Large), 4 ± 0.4 μm in length). The two MWCNTs were extensively characterized by SEM and TEM imaging, thermogravimetric analysis, and Brunauer-Emmett-Teller surface area analysis. Lung tissues were harvested 24h, 3 days and 28 days post-exposure. DNA microarrays were used to analyze gene expression, in parallel with analysis of bronchoalveolar lavage fluid, lung histology, DNA damage (comet assay) and the presence of reactive oxygen species (dichlorodihydrofluorescein assay), to profile and characterize related pulmonary endpoints. Overall changes in global transcription following exposure to CNT(Small) or CNT(Large) were similar. Both MWCNTs elicited strong acute phase and inflammatory responses that peaked at day 3, persisted up to 28 days, and were characterized by increased cellular influx in bronchoalveolar lavage fluid, interstitial pneumonia and gene expression changes. However, CNT(Large) elicited an earlier onset of inflammation and DNA damage, and induced more fibrosis and a unique fibrotic gene expression signature at day 28, compared to CNT(Small). The results indicate that the extent of change at the molecular level during early response phases following an acute exposure is greater in mice exposed to CNT(Large), which may eventually lead to the different responses observed at day 28.

Keywords: Acute phase response; DNA microarray; In vivo; Nanotoxicology; ROS production; Toxicogenomics.

Publication types

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

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • DNA Damage
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Inflammation Mediators / metabolism*
  • Inhalation Exposure / adverse effects
  • Lung / drug effects*
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Mice, Inbred C57BL
  • Nanotubes, Carbon / toxicity*
  • Particle Size
  • Pneumonia / chemically induced*
  • Pneumonia / genetics
  • Pneumonia / immunology
  • Pneumonia / metabolism
  • Pneumonia / pathology
  • Pulmonary Fibrosis / chemically induced*
  • Pulmonary Fibrosis / genetics
  • Pulmonary Fibrosis / immunology
  • Pulmonary Fibrosis / metabolism
  • Pulmonary Fibrosis / pathology
  • Reactive Oxygen Species
  • Risk Assessment
  • Surface Properties
  • Time Factors
  • Toxicogenetics / methods
  • Transcription, Genetic / drug effects*


  • Inflammation Mediators
  • Nanotubes, Carbon
  • Reactive Oxygen Species