TY  - JOUR
A1  - Ickrath, Pascal
A1  - Wagner, Martin
A1  - Scherzad, Agmal
A1  - Gehrke, Thomas
A1  - Burghartz, Marc
A1  - Hagen, Rudolf
A1  - Radeloff, Katrin
A1  - Kleinsasser, Norbert
A1  - Hackenberg, Stephan
T1  - Time-Dependent Toxic and Genotoxic Effects of Zinc Oxide Nanoparticles after Long-Term and Repetitive Exposure to Human Mesenchymal Stem Cells
JF  - International Journal of Environmental Research and Public Health
N2  - 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.
KW  - zinc oxide
KW  - ZnO
KW  - nanoparticles
KW  - cytotoxicity
KW  - toxicity
KW  - genotoxicity
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169932
VL  - 14
IS  - 12
ER  - 
TY  - JOUR
A1  - Meyer, Till Jasper
A1  - Stöth, Manuel
A1  - Moratin, Helena
A1  - Ickrath, Pascal
A1  - Herrmann, Marietta
A1  - Kleinsasser, Norbert
A1  - Hagen, Rudolf
A1  - Hackenberg, Stephan
A1  - Scherzad, Agmal
T1  - Cultivation of head and neck squamous cell carcinoma cells with wound fluid leads to cisplatin resistance via epithelial-mesenchymal transition induction
JF  - International Journal of Molecular Sciences
N2  - Locoregional recurrence is a major reason for therapy failure after surgical resection of head and neck squamous cell carcinoma (HNSCC). The physiological process of postoperative wound healing could potentially support the proliferation of remaining tumor cells. The aim of this study was to evaluate the influence of wound fluid (WF) on the cell cycle distribution and a potential induction of epithelial-mesenchymal transition (EMT). To verify this hypothesis, we incubated FaDu and HLaC78 cells with postoperative WF from patients after neck dissection. Cell viability in dependence of WF concentration and cisplatin was measured by flow cytometry. Cell cycle analysis was performed by flow cytometry and EMT-marker expression by rtPCR. WF showed high concentrations of interleukin (IL)-6, IL-8, IL-10, CCL2, MCP-1, EGF, angiogenin, and leptin. The cultivation of tumor cells with WF resulted in a significant increase in cell proliferation without affecting the cell cycle. In addition, there was a significant enhancement of the mesenchymal markers Snail 2 and vimentin, while the expression of the epithelial marker E-cadherin was significantly decreased. After cisplatin treatment, tumor cells incubated with WF showed a significantly higher resistance compared with the control group. The effect of cisplatin-resistance was dependent on the WF concentration. In summary, proinflammatory cytokines are predominantly found in WF. Furthermore, the results suggest that EMT can be induced by WF, which could be a possible mechanism for cisplatin resistance.
KW  - cell proliferation
KW  - wound fluid
KW  - epithelial-mesenchymal transition
KW  - cisplatin resistance
KW  - Interleukin
KW  - head and neck squamous cell carcinoma
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258722
SN  - 1422-0067
VL  - 22
IS  - 9
ER  -