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

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{sub Small}, 0.8 ± 0.1 μm in length) or large, thick MWCNT (CNT{sub 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 24 h, 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{sub Small} or CNT{sub 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{sub Large} elicited an earlier onset of inflammationmore » and DNA damage, and induced more fibrosis and a unique fibrotic gene expression signature at day 28, compared to CNT{sub 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{sub Large}, which may eventually lead to the different responses observed at day 28. - Highlights: • We evaluate the toxicogenomic response in mice following MWCNT instillation. • Two MWCNTs of different properties were examined and thoroughly characterized. • MWCNT exposure leads to increased pulmonary inflammation and acute phase response. • The thick and straight MWCNT induced transcriptional and histological pulmonary fibrotic changes. • This was not observed following exposure to the thinner and curled MWCNT.« less
Authors:
 [1] ;  [2] ;  [1] ;  [3] ;  [4] ;  [5] ;  [6] ;  [7] ;  [7] ;  [8] ;  [9] ;  [10] ;  [1] ;  [1] ;
  1. National Research Centre for the Working Environment, Copenhagen DK-2100 (Denmark)
  2. (Denmark)
  3. Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, Ontario K1A 0K9 (Canada)
  4. Department of Science, Systems and Models, Roskilde University, DK-4000 Roskilde (Denmark)
  5. Department of Micro- and Nanotechnology, Technical University of Denmark, DK-2800 Kgs. Lyngby (Denmark)
  6. Nanologica AB, SE-114 28 Stockholm (Sweden)
  7. Veneto Nanotech SCpA, ECSIN — European Centre for the Sustainable Impact of Nanotechnology, I-45100 Rovigo (Italy)
  8. Laboratory of Nanobiotechnology, National Institute for Research and Development in Microtechnologies, 077190 Bucharest (Romania)
  9. European Commission Joint Research Centre Institute for Environment and Sustainability, I-21027 Ispra, VA (Italy)
  10. National Food Institute, Technical University of Denmark, Søborg (Denmark)
Publication Date:
OSTI Identifier:
22465720
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 284; Journal Issue: 1; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACUTE EXPOSURE; ANIMAL TISSUES; CARBON NANOTUBES; DNA; DNA DAMAGES; FIBROSIS; FLUIDS; GENES; HAZARDS; HISTOLOGY; IN VIVO; INFLAMMATION; LENGTH; LUNGS; MICE; NANOMATERIALS; PNEUMONIA; SURFACE AREA; TRANSCRIPTION