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

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.

Toxicity and Functional Impairment in Human Adipose Tissue-Derived Stromal Cells (hASCs) Following Long-Term Exposure to Very Small Iron Oxide Particles (VSOPs)

“…Our study group previously demonstrated the intracellular accumulation and persistence of ZnO-NPs in hASCs after long-term cultivation [34,45]. Exposure of ZnO-NPs affected cell migration of hASCs [46], but not their ability to multidifferentiate [34,46]. The present study was conducted to add information on the effect of citrate-coated VSOPs on hASCs.…”

Cultivation of hMSCs in Human Plasma Prevents the Cytotoxic and Genotoxic Potential of ZnO-NP In Vitro

“…After dehydration of the specimens, embedding in Epon 812 and sectioning into ultrathin slices was performed. The slides were analyzed with an EM900 electron microscope (Carl Zeiss) and photographic negatives were digitalized by scanning [13,14].…”

The Impact of Metallic Nanoparticles on Stem Cell Proliferation and Differentiation

“…ZnO NP-associated toxicity of NSCs was aggravated in a concentration-dependent manner (due to the release of the Zn ions in the culture medium), whereas the size did not show a marked influence on ZnO NP toxicity [ 183 ]. The influence of the exposure time of ZnO NPs on the toxicity of hMSC was investigated [ 184 ]. In this study, exposure to high concentrations of ZnO NP and repetitive exposure to low doses led to ZnO NP-related toxicity in hMSCs, which led to the cellular accumulation of ZnO NP [ 184 ].…”

“…The influence of the exposure time of ZnO NPs on the toxicity of hMSC was investigated [ 184 ]. In this study, exposure to high concentrations of ZnO NP and repetitive exposure to low doses led to ZnO NP-related toxicity in hMSCs, which led to the cellular accumulation of ZnO NP [ 184 ]. ZnO NP-exposed mouse BM-MSCs (mBM-MSCs) showed a dose-dependent toxic action, which was attributed to high ROS production and the consequent activation of the apoptotic factors, namely caspase-3 and caspase-7 ( Figure 5 ) [ 185 ].…”