Genotoxic effects of zinc oxide nanoparticles in nasal mucosa cells are antagonized by titanium dioxide nanoparticles

Hackenberg, Stephan; Scherzed, Agmal; Zapp, Angela; Radeloff, Katrin; Ginzkey, Christian; Gehrke, Thomas; Ickrath, Pascal; Kleinsasser, Norbert

doi:10.1016/j.mrgentox.2017.02.005

Cited by 22 publications

(11 citation statements)

References 38 publications

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“…While Al 2 O 3 Nps were the only Nps that showed a clear protective effect in combination with ZnO Nps in Jurkat cells, TiO 2 Nps only protected the cells from MAPK and NFκB activation but not from the cytotoxic effect at concentrations <400 µg/mL. This finding is consistent with the results observed in human nasal mucosa, in which TiO 2 Nps were able to reduce the genotoxic effects induced by ZnO Nps, although changes in the cytotoxicity results were not found for the physical mixture of both Nps at a low concentration [ 38 ]. On the other hand, the combination of ZnO Nps with CeO 2 and Y 2 O 3 Nps also increased the toxicity at ≤400 µg/mL and the activation of p-p38 in a clear synergistic effect.…”

Section: Discussionsupporting

confidence: 84%

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Synergistic Effect of Metal Oxide Nanoparticles on Cell Viability and Activation of MAP Kinases and NFκB

Dávila-Grana

Diego-González

González-Fernández

et al. 2018

IJMS

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In recent years, there has been an increase in the production of several types of nanoparticles (Nps) for different purposes. Several studies have been performed to analyse the toxicity induced by some of these individual Nps, but data are scarce on the potential hazards or beneficial effects induced by a range of nanomaterials in the same environment. The purpose of the study described here was to evaluate the toxicological effects induced by in vitro exposure of human cells to ZnO Nps in combination with different concentrations of other metal oxide Nps (Al2O3, CeO2, TiO2 and Y2O3). The results indicate that the presence of these Nps has synergistic or antagonistic effects on the cell death induced by ZnO Nps, with a quite marked beneficial effect observed when high concentrations of Nps were tested. Moreover, analysis by Western blot of the main components of the intracellular activation routes (MAPKs and NFκB) again showed that the presence of other Nps can affect cell activation. In conclusion, the presence of several Nps in the same environment modifies the functional activity of one individual Np. Further studies are required in order to elucidate the effects induced by combinations of nanomaterials.

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Section: Discussionsupporting

confidence: 84%

“…ZnO Nps are partially soluble and an increase in their solubility could be related to the effect that these Nps have on cells. In fact, the matrix effect on the solubility of ZnO Nps has been described previously [ 37 , 38 ]. For instance, the presence of albumin increases the solubility of Nps.…”

Section: Discussionmentioning

confidence: 99%

Synergistic Effect of Metal Oxide Nanoparticles on Cell Viability and Activation of MAP Kinases and NFκB

Dávila-Grana

Diego-González

González-Fernández

et al. 2018

IJMS

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“…That is why the direct influence of ZnO-NP (in particular) on stem cells is coming into focus [ 9 ]. Our own studies have shown ZnO-NP to be responsible for cytotoxicity in nasal mucosa cells [ 30 , 31 ] or hMSC after short-term exposure [ 10 ]. The cancer-killing effects of ZnO-NP were described to begin at concentrations of 2.5 nM [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

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

Ickrath

Wagner

Scherzad

et al. 2017

IJERPH

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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.

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“…ZnO NPs are essential components of medical solutions, cosmetic products and dietary supplements. 49 There is no doubt that ZnO NPs come into contact with human cells in a variety of different ways; however, it is not clear exactly how they affect uncompromised cells and tissues. In this regard, a balance between human health risks and economic benefits has to be considered for nanomaterials in general.…”

Section: Discussionmentioning

confidence: 99%

“…15 In addition to these findings we could reveal comparable cytotoxic effects after repetitive exposure, DNA-damage after long-term and repetitive exposure and show functional impairment in the expression of VEGF and the formation of tubes. Numerous studies have proven that ZnO NPs induce DNA damage in various cell systems, 8,29,31,49 and determining the underlying mechanisms of these effects has been the objective of many recent investigations. The small size, large surface area and physicochemical characteristics of ZnO NPs, as well as the fact that they can be transferred into intracellular compartments via various mechanisms, are crucial factors in nanocytotoxicology and nanogenotoxicology of ZnO.…”

Section: Discussionmentioning

confidence: 99%

<p>Effects of Zinc Oxide Nanoparticles in HUVEC: Cyto- and Genotoxicity and Functional Impairment After Long-Term and Repetitive Exposure in vitro</p>

Poier¹,

Hochstöger²,

Hackenberg³

et al. 2020

IJN

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Purpose: The present study focuses on threshold levels for cytotoxicity after long-term and repetitive exposure for HUVEC as a model for the specific microvascular endothelial system. Furthermore, possible genotoxic effects and functional impairment caused by ZnO NPs in HUVEC are elucidated. Methods: Thresholds for cytotoxic effects are determined by the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) and Annexin V assay. To demonstrate DNA damage, single-cell microgel electrophoresis (comet) assay is performed after exposure to sub-cytotoxic concentrations of ZnO NPs. The proliferation assay, dot blot assay and capillary tube formation assay are also carried out to analyze functional impairment. Results: NPs showed to be spherical in shape with an average size of 45-55 nm. Long-term exposure as well as repetitive exposure with ZnO NPs exceeding 25 µg/mL lead to decreased viability in HUVEC. In addition, DNA damage was indicated by the comet assay after longterm and repetitive exposure. Twenty-four hours after long-term exposure, the proliferation assay does not show any difference between negative control and exposed cells. Forty-eight hours after exposure, HUVEC show an inverse concentration-related ability to proliferate. The dot blot assay provides evidence that ZnO NPs lead to a decreased release of VEGF, while capillary tube formation assay shows restriction in the ability of HUVEC to build tubes and meshes as a first step in angiogenesis. Conclusion: Sub-cytotoxic concentrations of ZnO NPs lead to DNA damage and functional impairment in HUVEC. Based on these data, ZnO NPs may affect neo-angiogenesis. Further investigation based on tissue cultures is required to elucidate the impact of ZnO NPs on human cell systems.

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Genotoxic effects of zinc oxide nanoparticles in nasal mucosa cells are antagonized by titanium dioxide nanoparticles

Cited by 22 publications

References 38 publications

Synergistic Effect of Metal Oxide Nanoparticles on Cell Viability and Activation of MAP Kinases and NFκB

Synergistic Effect of Metal Oxide Nanoparticles on Cell Viability and Activation of MAP Kinases and NFκB

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

<p>Effects of Zinc Oxide Nanoparticles in HUVEC: Cyto- and Genotoxicity and Functional Impairment After Long-Term and Repetitive Exposure in vitro</p>

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