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Author Poulsen, Sarah S. ♦ Saber, Anne T. ♦ Williams, Andrew ♦ Andersen, Ole ♦ Købler, Carsten ♦ Atluri, Rambabu ♦ Pozzebon, Maria E. ♦ Mucelli, Stefano P. ♦ Simion, Monica ♦ Rickerby, David ♦ Mortensen, Alicja ♦ Jackson, Petra ♦ Kyjovska, Zdenka O.
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword 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
Abstract 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 inflammation 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.
ISSN 0041008X
Educational Use Research
Learning Resource Type Article
Publisher Date 2015-04-01
Publisher Place United States
Journal Toxicology and Applied Pharmacology
Volume Number 284
Issue Number 1


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