DNA strand breaks, acute phase response and inflammation following pulmonary exposure by instillation to the diesel exhaust particle NIST1650b in mice

Zdenka O. Kyjovska, Nicklas R. Jacobsen, Anne T. Saber, Stefan Bengtson, Petra Jackson, Håkan Wallin, Ulla Birgitte Vogel

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    We investigated the inflammatory response, acute phase response and genotoxic effect of diesel exhaust particles (DEPs, NIST1650b) following a single intratracheal instillation. C57BL/6J BomTac mice received 18, 54 or 162 µg/mouse and were killed 1, 3 and 28 days post-exposure. Vehicle controls and the benchmark particle carbon black (CB, Printex 90; 162 µg/mouse) were tested alongside for comparison. The cellular composition and protein concentration were determined in bronchoalveolar lavage (BAL) fluid as markers for an inflammatory response. Pulmonary and systemic genotoxicity was analysed by the alkaline comet assay as DNA strand breaks in BAL cells, lung and liver tissue. The pulmonary acute phase response was analysed by Saa3 mRNA levels by real-time quantitative polymerase chain reaction. Instillation of DEP induced a strong neutrophil influx 1 and 3 days, but not 28 days post-exposure. Saa3 mRNA levels were increased at all time point for the highest dose and 28 days post-exposure for the middle dose. DEP increased levels of DNA strand breaks in lung tissue for all doses 1 day post-exposure and after 28 days for mid- and high-dose groups. Pulmonary exposure to DEP induced transient inflammation but long-lasting pulmonary acute phase response as well as genotoxicity in lung tissue 28 days post-exposure. The observed long-term pulmonary genotoxicity by DEP was less than the previously observed genotoxicity for CB using identical experimental set-up.
    Original languageEnglish
    JournalMutagenesis
    Volume30
    Issue number4
    Pages (from-to)499-507
    Number of pages9
    ISSN0267-8357
    DOIs
    Publication statusPublished - 2015

    Keywords

    • Original Manuscript

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