Journal article
MWCNTs of different physicochemical properties cause similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs
Roskilde University1
Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark2
National Food Institute, Technical University of Denmark3
Division of Risk Assessment and Nutrition, National Food Institute, Technical University of Denmark4
University of Copenhagen5
National Research Centre for the Working Environment6
Health Canada7
Department of Micro- and Nanotechnology, Technical University of Denmark8
Molecular Windows, Department of Micro- and Nanotechnology, Technical University of Denmark9
Nanologica AB10
European Centre for the Sustainable Impact of Nanotechnology11
National Institute for Research and Development in Microtechnologies Romania12
European Commission Joint Research Centre Institute13
...and 3 moreMulti-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 mu g/mouse of a small, curled (CNTsmall, 0.8 +/- 0.1 mu m in length) or large, thick MWCNT (CNTLarge, 4 +/- 0.4 mu m 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 bron-choalveolar 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 CNTsmall or CNTLarge 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, CNTLarge 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 CNTsmall. 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 CNTLarge, which may eventually lead to the different responses observed at day 28. (C) 2015 The Authors.
Published by Elsevier Inc.
Language: | English |
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Year: | 2015 |
Pages: | 16-32 |
ISSN: | 10960333 and 0041008x |
Types: | Journal article |
DOI: | 10.1016/j.taap.2014.12.011 |
ORCIDs: | Mølhave, Kristian |
Animals Bronchoalveolar Lavage Fluid DNA Damage Dose-Response Relationship, Drug Female Gene Expression Regulation Gene Regulatory Networks Inflammation Mediators Inhalation Exposure Lung Mice, Inbred C57BL Nanotubes, Carbon Particle Size Pneumonia Pulmonary Fibrosis Reactive Oxygen Species Risk Assessment Surface Properties Time Factors Toxicogenetics Transcription, Genetic