Toxicological characterization of ZnO nanoparticles in malignant and non‐malignant cells

Abstract

The increasing usage of zinc oxide nanoparticles (ZnO-NPs) in industrial applications as well as in consumer products raises concern regarding their potential adverse effects to a greater extend. Numerous studies have demonstrated toxic properties of NPs, however there is still a lack of knowledge concerning the underlying mechanisms. This study was designed to systematically investigate cytotoxicity, apoptosis, cell cycle alterations, and genotoxicity induced by ZnO-NP. Moreover, it was an aim of the investigations to specify the diverse effects of nanoparticle exposure in malignant in comparison with non-malignant cells. Therefore, human head and neck squamous cell carcinoma-derived FaDu cells were incubated with 4-20 µg/ml of ZnO-NPs for 1-48 hr and tested for cell viability, cell cycle alterations, apoptosis and caspase-3 gene expression as a sensitive marker of molecular apoptotic processes with regard to time- and dose-dependent effects. Human mesenchymal bone marrow stem cells were used as non-malignant representatives to examine oxidative stress-related genotoxicity. Results showed a significant reduction in cell viability as well as dose- and time-dependent increase of apoptotic cells following nanoparticle treatment. Likewise, caspase-3 gene expression enhanced already before first apoptotic cells were detectable. It could be observed that doses that were cytotoxic in tumor cells did not reduce viability in stem cells. However, the same concentrations already induced significant DNA damage. The findings of the study suggest to keep a more critical eye on the use of nanoparticles as anti-cancer agents. Yet, additional in vivo studies are needed to assess safety concerns for consumers and patients. Environ. Mol. Mutagen. 59:247-259, 2018. © 2017 Wiley Periodicals, Inc.

The Radiosensitizing Effect of Zinc Oxide Nanoparticles in Sub-Cytotoxic Dosing Is Associated with Oxidative Stress In Vitro

“…We observed an influence of ZnO-NP on the cell cycle in terms of G2/M arrest at high ZnO-NP concentrations. This ZnO-NP-mediated effect on the cell cycle was previously described by various other groups [17,43]. The increased radiation sensitivity in our experiments, even at low ZnO-NP concentrations, questions the ZnO-NP-mediated G2/M arrest as the main mechanism that causes radiation sensitivity.…”

“…The ZnO-NP were previously characterized by our group [17,18]. Transmission electron microscopy (TEM) (Zeiss transmission electron microscope EM 900, Carl Zeiss, Oberkochen, Germany) was used to assess particle size distribution and morphology at the Division of Electron Microscopy at the Biocenter of University of Würzburg.…”

Zinc oxide nanoparticles induce toxicity in CAL 27 oral cancer cell lines by activating PINK1/Parkin-mediated mitophagy

“…These results are consistent with findings from previous studies. 10,25 ZnO NP-induced cytotoxicity in cancer cells is associated with ROS production. Chakraborti et al claimed that PEG-modified ZnO NPs display anticancer properties mainly due to the formation of ROS.…”

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

“…As a reference, the pure medium with supplements was measured at the four time points (0 h, 4 h, 8 h, and 12 h). We assessed the percentage of non-sedimented NP, defining the measurement at 0 h as 100% and the cell culture medium without NP as 0% [ 13 ]. Characterization of shape and single particle size was performed by transmission electron microscopy (see Section 2.7 ).…”