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Reactive oxygen species independent genotoxicity of indium tin oxide nanoparticles triggered by intracellular degradation

Author:
Tabei, Yosuke, Sugino, Sakiko, Nakajima, Yoshihiro, Horie, Masanori
Source:
Food and chemical toxicology 2018 v.118 pp. 264-271
ISSN:
0278-6915
Subject:
DNA damage, acetylcysteine, ammonium chloride, atomic absorption spectrometry, electrodes, epithelium, genotoxicity, health hazards, humans, indium, indium tin oxide, ions, lungs, mutagens, nanoparticles, occupational exposure, reactive oxygen species, solubility, solubilization, toxicology
Abstract:
Indium tin oxide (ITO) is widely used as a transparent conducting electrode in photoelectron devices. Because ITO production has soared, the potential health hazards caused by occupational exposure to this material have attracted much attention. However, little is known about the mechanisms of the toxic action of ITO nanoparticles (NPs). The present study was designed to examine the genotoxic mechanisms of ITO NPs using human lung epithelial A549 cells. We found that exposing A549 cells to ITO NPs triggered the intracellular accumulation of ITO NPs, the generation of reactive oxygen species (ROS), and the induction of DNA damage. Treatment of the cells with N-acetyl-l-cysteine (NAC), an ROS quenching agent, decreased intracellular ROS levels but not DNA damage, indicating that the genotoxic effect of ITO NPs is not mediated by intracellular ROS. Interestingly, treatment with ammonium chloride, a lysosomotropic agent, decreased intracellular solubility of ITO NPs and attenuated DNA damage. Nuclear accumulation of indium ions in ITO-NP-exposed cells was confirmed by inductively coupled plasma-mass spectrometry. Our results indicate that the ITO-NP-mediated genotoxicity is caused by indium ions that are solubilized in the acidic lysosomal condition and accumulated in the nucleus where they damage DNA, without the involvement of ROS.
Agid:
6106181