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

Sarah Søs Poulsen, Anne Saber, Andrew Williams, Ole Andersen, Carsten Købler, Rambabu Atluri, Maria E. Pozzebon, Stefano P. Mucelli, Monica Simion, David Rickerby, Alicja Mortensen, Petra Jackson, Zdenka Kyjovska, Kristian Mølhave, Nicklas R. Jacobsen, Keld Alstrup Jensen, Carole Yauk, Håkan Wallin, Sabina Halappanavar, Ulla Vogel

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    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 (CNTSmall, 0.8 ± 0.1 μm in length) or large, thick MWCNT (CNTLarge, 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 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.
    OriginalsprogEngelsk
    TidsskriftToxicology and Applied Pharmacology
    Vol/bind284
    Udgave nummer1
    Sider (fra-til)16-32
    ISSN0041-008X
    DOI
    StatusUdgivet - 2015

    Bibliografisk note

    The project was supported by grants fromthe National Research Centre
    for theWorking Environment inDenmark and the Danish NanoSafety
    Center, grant# 20110092173-3, the European Community's Seventh
    Framework Programme (FP7/2007-2013) under grant agreement
    #247989 (Nanosustain), and Health Canada's Chemical Management
    Plan-2 Nano research funds and Genomics Research and Development
    Initiative. The funders had no role in study design, data collection and
    analysis, decision to publish, or preparation of the manuscript.

    Citer dette

    Poulsen, S. S., Saber, A., Williams, A., Andersen, O., Købler, C., Atluri, R., Pozzebon, M. E., Mucelli, S. P., Simion, M., Rickerby, D., Mortensen, A., Jackson, P., Kyjovska, Z., Mølhave, K., Jacobsen, N. R., Alstrup Jensen, K., Yauk, C., Wallin, H., Halappanavar, S., & Vogel, U. (2015). MWCNTs of different physicochemical properties cause similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs. Toxicology and Applied Pharmacology, 284(1), 16-32. https://doi.org/10.1016/j.taap.2014.12.011