Differences in inflammation and acute phase response but similar genotoxicity in mice following pulmonary exposure to graphene oxide and reduced graphene oxide

Stefan Bengtson, Kristina Bram Knudsen, Zdenka O. Kyjovska, Trine Berthing, Vidar Skaug, Marcus Levin, Ismo K. Koponen, Abhay Shivayogimath, Tim Booth, Beatriz Alonso, Amaia Pesquera, Amaia Zurutuza, Birthe L. Thomsen, Jesper T. Troelsen, Nicklas R. Jacobsen, Ulla Birgitte Vogel

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    Abstract

    We investigated toxicity of 2-3 layered >1 μm sized graphene oxide (GO) and reduced graphene oxide (rGO) in mice following single intratracheal exposure with respect to pulmonary inflammation, acute phase response (biomarker for risk of cardiovascular disease) and genotoxicity. In addition, we assessed exposure levels of particulate matter emitted during production of graphene in a clean room and in a normal industrial environment using chemical vapour deposition. Toxicity was evaluated at day 1, 3, 28 and 90 days (18, 54 and 162 μg/mouse), except for GO exposed mice at day 28 and 90 where only the lowest dose was evaluated. GO induced a strong acute inflammatory response together with a pulmonary (Serum-Amyloid A, Saa3) and hepatic (Saa1) acute phase response. rGO induced less acute, but a constant and prolonged inflammation up to day 90. Lung histopathology showed particle agglomerates at day 90 without signs of fibrosis. In addition, DNA damage in BAL cells was observed across time points and doses for both GO and rGO. In conclusion, pulmonary exposure to GO and rGO induced inflammation, acute phase response and genotoxicity but no fibrosis.
    Original languageEnglish
    JournalP L o S One
    Volume12
    Issue number6
    Pages (from-to)e0178355
    Number of pages25
    ISSN1932-6203
    DOIs
    Publication statusPublished - 2017

    Cite this

    Bengtson, Stefan ; Knudsen, Kristina Bram ; Kyjovska, Zdenka O. ; Berthing, Trine ; Skaug, Vidar ; Levin, Marcus ; Koponen, Ismo K. ; Shivayogimath, Abhay ; Booth, Tim ; Alonso, Beatriz ; Pesquera, Amaia ; Zurutuza, Amaia ; Thomsen, Birthe L. ; Troelsen, Jesper T. ; Jacobsen, Nicklas R. ; Vogel, Ulla Birgitte. / Differences in inflammation and acute phase response but similar genotoxicity in mice following pulmonary exposure to graphene oxide and reduced graphene oxide. In: P L o S One. 2017 ; Vol. 12, No. 6. pp. e0178355.
    @article{ba70bf7436dd47a8a1cb97438e92e246,
    title = "Differences in inflammation and acute phase response but similar genotoxicity in mice following pulmonary exposure to graphene oxide and reduced graphene oxide",
    abstract = "We investigated toxicity of 2-3 layered >1 μm sized graphene oxide (GO) and reduced graphene oxide (rGO) in mice following single intratracheal exposure with respect to pulmonary inflammation, acute phase response (biomarker for risk of cardiovascular disease) and genotoxicity. In addition, we assessed exposure levels of particulate matter emitted during production of graphene in a clean room and in a normal industrial environment using chemical vapour deposition. Toxicity was evaluated at day 1, 3, 28 and 90 days (18, 54 and 162 μg/mouse), except for GO exposed mice at day 28 and 90 where only the lowest dose was evaluated. GO induced a strong acute inflammatory response together with a pulmonary (Serum-Amyloid A, Saa3) and hepatic (Saa1) acute phase response. rGO induced less acute, but a constant and prolonged inflammation up to day 90. Lung histopathology showed particle agglomerates at day 90 without signs of fibrosis. In addition, DNA damage in BAL cells was observed across time points and doses for both GO and rGO. In conclusion, pulmonary exposure to GO and rGO induced inflammation, acute phase response and genotoxicity but no fibrosis.",
    author = "Stefan Bengtson and Knudsen, {Kristina Bram} and Kyjovska, {Zdenka O.} and Trine Berthing and Vidar Skaug and Marcus Levin and Koponen, {Ismo K.} and Abhay Shivayogimath and Tim Booth and Beatriz Alonso and Amaia Pesquera and Amaia Zurutuza and Thomsen, {Birthe L.} and Troelsen, {Jesper T.} and Jacobsen, {Nicklas R.} and Vogel, {Ulla Birgitte}",
    year = "2017",
    doi = "10.1371/journal.pone.0178355",
    language = "English",
    volume = "12",
    pages = "e0178355",
    journal = "P L o S One",
    issn = "1932-6203",
    publisher = "Public Library of Science",
    number = "6",

    }

    Bengtson, S, Knudsen, KB, Kyjovska, ZO, Berthing, T, Skaug, V, Levin, M, Koponen, IK, Shivayogimath, A, Booth, T, Alonso, B, Pesquera, A, Zurutuza, A, Thomsen, BL, Troelsen, JT, Jacobsen, NR & Vogel, UB 2017, 'Differences in inflammation and acute phase response but similar genotoxicity in mice following pulmonary exposure to graphene oxide and reduced graphene oxide', P L o S One, vol. 12, no. 6, pp. e0178355. https://doi.org/10.1371/journal.pone.0178355

    Differences in inflammation and acute phase response but similar genotoxicity in mice following pulmonary exposure to graphene oxide and reduced graphene oxide. / Bengtson, Stefan; Knudsen, Kristina Bram; Kyjovska, Zdenka O.; Berthing, Trine; Skaug, Vidar; Levin, Marcus; Koponen, Ismo K.; Shivayogimath, Abhay; Booth, Tim ; Alonso, Beatriz; Pesquera, Amaia; Zurutuza, Amaia; Thomsen, Birthe L.; Troelsen, Jesper T.; Jacobsen, Nicklas R.; Vogel, Ulla Birgitte.

    In: P L o S One, Vol. 12, No. 6, 2017, p. e0178355.

    Research output: Contribution to journalJournal articleResearchpeer-review

    TY - JOUR

    T1 - Differences in inflammation and acute phase response but similar genotoxicity in mice following pulmonary exposure to graphene oxide and reduced graphene oxide

    AU - Bengtson, Stefan

    AU - Knudsen, Kristina Bram

    AU - Kyjovska, Zdenka O.

    AU - Berthing, Trine

    AU - Skaug, Vidar

    AU - Levin, Marcus

    AU - Koponen, Ismo K.

    AU - Shivayogimath, Abhay

    AU - Booth, Tim

    AU - Alonso, Beatriz

    AU - Pesquera, Amaia

    AU - Zurutuza, Amaia

    AU - Thomsen, Birthe L.

    AU - Troelsen, Jesper T.

    AU - Jacobsen, Nicklas R.

    AU - Vogel, Ulla Birgitte

    PY - 2017

    Y1 - 2017

    N2 - We investigated toxicity of 2-3 layered >1 μm sized graphene oxide (GO) and reduced graphene oxide (rGO) in mice following single intratracheal exposure with respect to pulmonary inflammation, acute phase response (biomarker for risk of cardiovascular disease) and genotoxicity. In addition, we assessed exposure levels of particulate matter emitted during production of graphene in a clean room and in a normal industrial environment using chemical vapour deposition. Toxicity was evaluated at day 1, 3, 28 and 90 days (18, 54 and 162 μg/mouse), except for GO exposed mice at day 28 and 90 where only the lowest dose was evaluated. GO induced a strong acute inflammatory response together with a pulmonary (Serum-Amyloid A, Saa3) and hepatic (Saa1) acute phase response. rGO induced less acute, but a constant and prolonged inflammation up to day 90. Lung histopathology showed particle agglomerates at day 90 without signs of fibrosis. In addition, DNA damage in BAL cells was observed across time points and doses for both GO and rGO. In conclusion, pulmonary exposure to GO and rGO induced inflammation, acute phase response and genotoxicity but no fibrosis.

    AB - We investigated toxicity of 2-3 layered >1 μm sized graphene oxide (GO) and reduced graphene oxide (rGO) in mice following single intratracheal exposure with respect to pulmonary inflammation, acute phase response (biomarker for risk of cardiovascular disease) and genotoxicity. In addition, we assessed exposure levels of particulate matter emitted during production of graphene in a clean room and in a normal industrial environment using chemical vapour deposition. Toxicity was evaluated at day 1, 3, 28 and 90 days (18, 54 and 162 μg/mouse), except for GO exposed mice at day 28 and 90 where only the lowest dose was evaluated. GO induced a strong acute inflammatory response together with a pulmonary (Serum-Amyloid A, Saa3) and hepatic (Saa1) acute phase response. rGO induced less acute, but a constant and prolonged inflammation up to day 90. Lung histopathology showed particle agglomerates at day 90 without signs of fibrosis. In addition, DNA damage in BAL cells was observed across time points and doses for both GO and rGO. In conclusion, pulmonary exposure to GO and rGO induced inflammation, acute phase response and genotoxicity but no fibrosis.

    U2 - 10.1371/journal.pone.0178355

    DO - 10.1371/journal.pone.0178355

    M3 - Journal article

    VL - 12

    SP - e0178355

    JO - P L o S One

    JF - P L o S One

    SN - 1932-6203

    IS - 6

    ER -