Pulmonary instillation of low doses of titanium dioxide nanoparticles in mice leads to particle retention and gene expression changes in the absence of inflammation

Mainul Husain, Anne Thoustrup Saber, Charles Guo, Nicklas R. Jacobsen, Keld Almand Jensen, Carole L. Yauk, Andrew Richard Williams, Ulla Birgitte Vogel, Hakan Wallin, Sabina Halappanavar

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    Abstract

    We investigated gene expression, protein synthesis, and particle retention in mouse lungs following intratracheal instillation of varying doses of nano-sized titanium dioxide (nano-TiO2). Female C57BL/6 mice were exposed to rutile nano-TiO2 via single intratracheal instillations of 18, 54, and 162μg/mouse. Mice were sampled 1, 3, and 28days post-exposure. The deposition of nano-TiO2 in the lungs was assessed using nanoscale hyperspectral microscopy. Biological responses in the pulmonary system were analyzed using DNA microarrays, pathway-specific real-time RT-PCR (qPCR), gene-specific qPCR arrays, and tissue protein ELISA. Hyperspectral mapping showed dose-dependent retention of nano-TiO2 in the lungs up to 28days post-instillation. DNA microarray analysis revealed approximately 3000 genes that were altered across all treatment groups (±1.3 fold; p
    Original languageEnglish
    JournalToxicology and Applied Pharmacology
    Volume269
    Issue number3
    Pages (from-to)250-262
    ISSN0041-008X
    DOIs
    Publication statusPublished - 2013

    Keywords

    • Hyperspectral microscopy
    • Gene expression
    • Inflammation
    • Muscle contraction
    • Calcium homeostasis
    • Tissue particle retention

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