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

Tidsskriftartikel - 2015

Resume

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 162mug/mouse of a small, curled (CNTSmall, 0.8+/-0.1mum in length) or large, thick MWCNT (CNTLarge, 4+/-0.4mum 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, 3days and 28days 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 CNTSmall or CNTLarge were similar. Both MWCNTs elicited strong acute phase and inflammatory responses that peaked at day 3, persisted up to 28days, 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

Reference

Poulsen SS, Saber AT, Williams A, Andersen O, Kobler C, Atluri R, Pozzebon M, Mucelli S, Simion M, Rickerby D, Mortensen A, Jackson P, Kyjovska Z, Molhave K, Jacobsen NR, Jensen KA, Yauk C, Wallin EHR, Halappanavar S, Vogel UB. MWCNTs of different physicochemical properties causes similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs. Toxicology and Applied Pharmacology 2015;284(1):16-32.
doi: 10.1016/j.taap.2014.12.011

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Dansk Center for Nanosikkerhed