Molecular mechanism of DNA damage induced by titanium dioxide nanoparticles in toll-like receptor 3 or 4 expressing human hepatocarcinoma cell lines

Karim Samy El-Said, Ehab Mostafa Ali, Koki Kanehira, Akiyoshi Taniguchi

    Research output: Contribution to journalArticle

    28 Citations (Scopus)

    Abstract

    Background: Titanium dioxide nanoparticles (TiO2 NPs) are widely used in the biological sciences. The increasing use of TiO2 NPs increases the risk of humans and the environment being exposed to NPs. We previously showed that toll-like receptors (TLRs) play an important role in the interactions between NPs and cells. Our previous results indicated that TLR4 increased the DNA damage response induced by TiO2 NPs, due to enhanced NP uptake into the cytoplasm, whereas TLR3 expression decreased the DNA damage response induced by TiO2 NPs because of NP retention in the endosome. In this study, we explored the molecular mechanism of the DNA damage response induced by TiO2 NPs using TLR3 or TLR4 transfected cells. We examined the effect of TLR3 or TLR4 over-expression on oxidative stress and the effect of DNA damage induced by TiO2 NPs on gene expression levels. Results: Our results showed evidence for elevated oxidative stress, including the generation of reactive oxygen species (ROS), with increased hydrogen peroxide levels, decreased glutathione peroxidase, and reduced glutathione and activated caspase-3 levels in cells exposed for 48 h to 10 μg/ml TiO2 NPs. These effects were enhanced by TLR4 and reduced by TLR3 over-expression. Seventeen genes related to DNA double-strand breaks and apoptosis were induced, particularly IP6K3 and ATM. Conclusion: Our results indicated that TiO2 NPs induced ROS, and the above molecules are implicated in the genotoxicity induced by TiO2 NPs.

    Original languageEnglish
    Article number48
    JournalJournal of Nanobiotechnology
    Volume12
    Issue number1
    DOIs
    Publication statusPublished - 2014 Dec 2

    Fingerprint

    Toll-Like Receptor 3
    Toll-Like Receptor 4
    Nanoparticles
    Titanium dioxide
    DNA Damage
    DNA
    Cells
    Cell Line
    Oxidative stress
    Reactive Oxygen Species
    Oxidative Stress
    Double-Stranded DNA Breaks
    Biological Science Disciplines
    Toll-Like Receptors
    Endosomes
    Glutathione Peroxidase
    Oxygen
    Caspase 3
    Hydrogen Peroxide
    Glutathione

    Keywords

    • Apoptosis
    • DNA damage
    • ROS
    • TiO NPs
    • TLRs

    ASJC Scopus subject areas

    • Molecular Medicine
    • Bioengineering
    • Biomedical Engineering
    • Applied Microbiology and Biotechnology
    • Medicine (miscellaneous)
    • Pharmaceutical Science

    Cite this

    Molecular mechanism of DNA damage induced by titanium dioxide nanoparticles in toll-like receptor 3 or 4 expressing human hepatocarcinoma cell lines. / El-Said, Karim Samy; Ali, Ehab Mostafa; Kanehira, Koki; Taniguchi, Akiyoshi.

    In: Journal of Nanobiotechnology, Vol. 12, No. 1, 48, 02.12.2014.

    Research output: Contribution to journalArticle

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