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Int J Environ Res Public Health. 2017 Dec 18;14(12). pii: E1590. doi: 10.3390/ijerph14121590.

Time-Dependent Toxic and Genotoxic Effects of Zinc Oxide Nanoparticles after Long-Term and Repetitive Exposure to Human Mesenchymal Stem Cells.

Author information

1
Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University of Wuerzburg, 97080 Würzburg, Germany. ickrath_p@ukw.de.
2
Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University of Wuerzburg, 97080 Würzburg, Germany. wagnermartin924@gmail.com.
3
Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University of Wuerzburg, 97080 Würzburg, Germany. scherzad_a@ukw.de.
4
Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University of Wuerzburg, 97080 Würzburg, Germany. gehrke_t@ukw.de.
5
Department of Otorhinolaryngology, Head and Neck Surgery, Katharinenhospital Stuttgart, 70174 Stuttgart, Germany. m.burghartz@klinikum-stuttgart.de.
6
Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University of Wuerzburg, 97080 Würzburg, Germany. hagen_r@ukw.de.
7
Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University of Wuerzburg, 97080 Würzburg, Germany. radeloff_k@ukw.de.
8
Department of Otorhinolaryngology, Head and Neck Surgery, Kepler University Hospital, 4021 Linz, Austria. Norbert.Kleinsasser@kepleruniklinikum.at.
9
Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University of Wuerzburg, 97080 Würzburg, Germany. hackenberg_s@ukw.de.

Abstract

Zinc oxide nanoparticles (ZnO-NP) are widely spread in consumer products. Data about the toxicological characteristics of ZnO-NP is still under controversial discussion. The human skin is the most important organ concerning ZnO-NP exposure. Intact skin was demonstrated to be a sufficient barrier against NPs; however, defect skin may allow NP contact to proliferating cells. Within these cells, stem cells are the most important toxicological target for NPs. The aim of this study was to evaluate the genotoxic and cytotoxic effects of ZnO-NP at low-dose concentrations after long-term and repetitive exposure to human mesenchymal stem cells (hMSC). Cytotoxic effects of ZnO-NP were measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Furthermore, genotoxicity was evaluated by the comet assay. For long-term observation over 6 weeks, transmission electron microscopy (TEM) was applied. The results of the study indicated cytotoxic effects of ZnO-NP beginning at high concentrations of 50 μg/mL and genotoxic effects in hMSC exposed to 1 and 10 μg/mL ZnO-NP. Repetitive exposure enhanced cyto- but not genotoxicity. Intracellular NP accumulation was observed up to 6 weeks. The results suggest cytotoxic and genotoxic potential of ZnO-NP. Even low doses of ZnO-NP may induce toxic effects as a result of repetitive exposure and long-term cellular accumulation. This data should be considered before using ZnO-NP on damaged skin.

KEYWORDS:

ZnO; cytotoxicity; genotoxicity; nanoparticles; toxicity; zinc oxide

PMID:
29258234
PMCID:
PMC5751007
DOI:
10.3390/ijerph14121590
[Indexed for MEDLINE]
Free PMC Article

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