Dataset Information

Calcium-dependent cyto- and genotoxicity of nickel metal and nickel oxide nanoparticles in human lung cells.

ABSTRACT:

Background

Genotoxicity is an important toxicological endpoint due to the link to diseases such as cancer. Therefore, an increased understanding regarding genotoxicity and underlying mechanisms is needed for assessing the risk with exposure to nanoparticles (NPs). The aim of this study was to perform an in-depth investigation regarding the genotoxicity of well-characterized Ni and NiO NPs in human bronchial epithelial BEAS-2B cells and to discern possible mechanisms. Comparisons were made with NiCl₂ in order to elucidate effects of ionic Ni.

Methods

BEAS-2B cells were exposed to Ni and NiO NPs, as well as NiCl₂, and uptake and cellular dose were investigated by transmission electron microscopy (TEM) and inductively coupled plasma mass spectrometry (ICP-MS). The NPs were characterized in terms of surface composition (X-ray photoelectron spectroscopy), agglomeration (photon cross correlation spectroscopy) and nickel release in cell medium (ICP-MS). Cell death (necrosis/apoptosis) was investigated by Annexin V-FITC/PI staining and genotoxicity by cytokinesis-block micronucleus (cytome) assay (OECD 487), chromosomal aberration (OECD 473) and comet assay. The involvement of intracellular reactive oxygen species (ROS) and calcium was explored using the fluorescent probes, DCFH-DA and Fluo-4.

Results

NPs were efficiently taken up by the BEAS-2B cells. In contrast, no or minor uptake was observed for ionic Ni from NiCl₂. Despite differences in uptake, all exposures (NiO, Ni NPs and NiCl₂) caused chromosomal damage. Furthermore, NiO NPs were most potent in causing DNA strand breaks and generating intracellular ROS. An increase in intracellular calcium was observed and modulation of intracellular calcium by using inhibitors and chelators clearly prevented the chromosomal damage. Chelation of iron also protected against induced damage, particularly for NiO and NiCl₂.

Conclusions

This study has revealed chromosomal damage by Ni and NiO NPs as well as Ni ionic species and provides novel evidence for a calcium-dependent mechanism of cyto- and genotoxicity.

SUBMITTER: Di Bucchianico S

PROVIDER: S-EPMC6050732 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Publications

Calcium-dependent cyto- and genotoxicity of nickel metal and nickel oxide nanoparticles in human lung cells.

Di Bucchianico Sebastiano S Gliga Anda R AR Åkerlund Emma E Skoglund Sara S Wallinder Inger Odnevall IO Fadeel Bengt B Karlsson Hanna L HL

Particle and fibre toxicology 20180717 1

<h4>Background</h4>Genotoxicity is an important toxicological endpoint due to the link to diseases such as cancer. Therefore, an increased understanding regarding genotoxicity and underlying mechanisms is needed for assessing the risk with exposure to nanoparticles (NPs). The aim of this study was to perform an in-depth investigation regarding the genotoxicity of well-characterized Ni and NiO NPs in human bronchial epithelial BEAS-2B cells and to discern possible mechanisms. Comparisons were mad ...[more]

PMID: 30016969

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Project description:BackgroundThe rapid expansion of manufacturing and use of nano-sized materials fuels the demand for fast and reliable assays to identify their potential hazardous properties and underlying mechanisms. The ToxTracker assay is a recently developed mechanism-based reporter assay based on mouse embryonic stem (mES) cells that uses GFP-tagged biomarkers for detection of DNA damage, oxidative stress and general cellular stress upon exposure. Here, we evaluated the ability of the ToxTracker assay to identify the hazardous properties and underlying mechanisms of a panel of metal oxide- and silver nanoparticles (NPs) as well as additional non-metallic materials (diesel, carbon nanotubes and quartz).MethodsThe metal oxide- and silver nanoparticles were characterized in terms of agglomeration and ion release in cell medium (using photon cross correlation spectroscopy and inductively coupled plasma with optical emission spectroscopy, respectively) as well as acellular ROS production (DCFH-DA assay). Cellular uptake was investigated by means of transmission electron microscopy. GFP reporter induction and cytotoxicity of the NPs was simultaneously determined using flow cytometry, and genotoxicity was further tested using conventional assays (comet assay, γ-H2AX and RAD51 foci formation).ResultsWe show that the reporter cells were able to take up nanoparticles and, furthermore, that exposure to CuO, NiO and ZnO nanoparticles as well as to quartz resulted in activation of the oxidative stress reporter, although only at high cytotoxicity for ZnO. NiO NPs activated additionally a p53-associated cellular stress response, indicating additional reactive properties. Conventional assays for genotoxicity assessment confirmed the response observed in the ToxTracker assay. We show for CuO NPs that the induction of oxidative stress is likely the consequence of released Cu ions whereas the effect by NiO was related to the particles per se. The DNA replication stress-induced reporter, which is most strongly associated with carcinogenicity, was not activated by any of the tested nanoparticles.ConclusionsWe conclude that the ToxTracker reporter system can be used as a rapid mechanism-based tool for the identification of hazardous properties of metal oxide NPs. Furthermore, genotoxicity of metal oxide NPs seems to occur mainly via oxidative stress rather than direct DNA binding with subsequent replication stress.

Project description:BackgroundAlthough zinc oxide nanoparticles (ZnO NPs) have been widely used, there has been an increasing number of reports on the toxicity of ZnO NPs. However, study on the underlying mechanisms under in vivo conditions is insufficient.MethodsIn this study, we investigated the toxicological profiles of ZnO NPs in MRC5 human lung fibroblasts in vitro and in an in vivo model using the fruit fly Drosophila melanogaster. A comprehensive study was conducted to evaluate the uptake, cytotoxicity, reactive oxygen species (ROS) formation, gene expression profiling and genotoxicity induced by ZnO NPs.ResultsFor in vitro toxicity, the results showed that there was a significant release of extracellular lactate dehydrogenase and decreased cell viability in ZnO NP-treated MRC5 lung cells, indicating cellular damage and cytotoxicity. Generation of ROS was observed to be related to significant expression of DNA Damage Inducible Transcript (DDIT3) and endoplasmic reticulum (ER) to nucleus signaling 1 (ERN1) genes, which are ER stress-related genes. Oxidative stress induced DNA damage was further verified by a significant release of DNA oxidation product, 8-hydroxydeoxyguanosine (8-OHdG), as well as by the Comet assay. For the in vivo study using the fruit fly D. melanogaster as a model, significant toxicity was observed in F1 progenies upon ingestion of ZnO NPs. ZnO NPs induced significant decrease in the egg-to-adult viability of the flies. We further showed that the decreased viability is closely associated with ROS induction by ZnO NPs. Removal of one copy of the D. melanogaster Nrf2 alleles further decreased the ZnO NPs-induced lethality due to increased production of ROS, indicating that nuclear factor E2-related factor 2 (Nrf2) plays important role in ZnO NPs-mediated ROS production.ConclusionThe present study suggests that ZnO NPs induced significant oxidative stress-related cytotoxicity and genotoxicity in human lung fibroblasts in vitro and in D. melanogaster in vivo. More extensive studies would be needed to verify the safety issues related to increased usage of ZnO NPs by consumers.

Dataset Information

Calcium-dependent cyto- and genotoxicity of nickel metal and nickel oxide nanoparticles in human lung cells.

Background

Methods

Results

Conclusions

Publications

Calcium-dependent cyto- and genotoxicity of nickel metal and nickel oxide nanoparticles in human lung cells.

Similar Datasets

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