Journal Article

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

Fadeel, Bengt, Di Bucchianico, Sebastiano, Wallinder, Inger Odnevall, Skoglund, Sara, Karlsson, Hanna L., Åkerlund, Emma, Gliga, Anda R.

2018

Overview

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 NiCl 2 in order to elucidate effects of ionic Ni. Methods BEAS-2B cells were exposed to Ni and NiO NPs, as well as NiCl 2 , 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 NiCl 2 . Despite differences in uptake, all exposures (NiO, Ni NPs and NiCl 2 ) 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 NiCl 2 . 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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Annexin V / Apoptosis / Bioassays / Bioavailability / Biochemical toxicology / Biomedical and Life Sciences / Biomedicine / Calcium / Calcium (intracellular) / Calcium (Nutrient) / Calcium homeostasis / Cancer / Carcinogenic potential / Cell death / Chelating agents / Chelation / Chromosomal aberrations / Chromosome aberrations / Comet assay / Cross correlation / Cytokinesis / Damage detection / Damage prevention / Deoxyribonucleic acid / DNA / DNA damage / DNA probes / Emission spectroscopy / Endoreduplication / Environmental Health / Exposure / Fluorescent indicators / Gangrene / Gene expression / Genetic toxicology / Genotoxicity / Health aspects / Homeostasis / Inductively coupled plasma mass spectrometry / Intracellular / Lung / Lung cancer / Lymphocytes / Mass spectrometry / Mass spectroscopy / Medical research / Nanoparticles / Nanotechnology / Necrosis / Nickel / Nickel (Metal) / Nickel chloride / Nickel compounds / Nickel oxides / Nickel/nickel oxide nanoparticles / Oxidative stress / Pharmacology/Toxicology / Photoelectron spectroscopy / Photoelectrons / Physiological aspects / Pneumology/Respiratory System / Public Health / Quantum dots / Reactive oxygen species / Risk assessment / Rodents / Spectroscopy / Steel production / Studies / Transmission electron microscopy / Tumors