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Evaluation of cytotoxicity and genotoxicity induced by oleic acid-coated iron oxide nanoparticles in human astrocytes
Authors:Natalia Fernández-Bertólez  Carla Costa  Fátima Brandão  José Alberto Duarte  Joao Paulo Teixeira  Eduardo Pásaro  Vanessa Valdiglesias  Blanca Laffon
Institution:1. Department of Psychology, Area of Psychobiology, Edificio de Servicios Centrales de Investigación, Universidade da Coruña, DICOMOSA Group, Campus Elviña s/n, 15071-A Coruña, Spain

Department of Cell and Molecular Biology, Facultad de Ciencias, Universidade da Coruña, Campus A Zapateira s/n, 15071-A Coruña, Spain;2. Department of Environmental Health, Portuguese National Institute of Health, Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal

EPIUnit – Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas, 135, 4050-600 Porto, Portugal;3. CIAFEL, Faculdade de Desporto, Universidade do Porto, Rua Dr. Plácido Costa, 91, 4200-450 Porto, Portugal;4. Department of Psychology, Area of Psychobiology, Edificio de Servicios Centrales de Investigación, Universidade da Coruña, DICOMOSA Group, Campus Elviña s/n, 15071-A Coruña, Spain

Abstract:Iron oxide nanoparticles (ION) are gaining importance as diagnostic and therapeutic tool of central nervous system diseases. Although oleic acid-coated ION (O-ION) have been described as stable and biocompatible, their potential neurotoxicity was scarcely evaluated in human nervous cells so far. The primary aim of this work was to assess the molecular and cellular effects of O-ION on human astrocytes (A172 cells) under different experimental conditions. An extensive set of cyto- and genotoxicity tests was carried out, including lactate dehydrogenase release assay, cell cycle alterations, and cell death production, as well as comet assay, γH2AX assay, and micronucleus (MN) test, considering also iron ion release capacity and alterations in DNA repair ability. Results showed a moderate cytotoxicity related to cell cycle arrest and cell death promotion, regardless of serum presence. O-ION induced genotoxic effects, namely primary DNA damage, as detected by the comet assay and H2AX phosphorylation, but A172 cells were able to repair this particular damage because no chromosome alterations were found (confirmed by MN test results). Accordingly, no effects on the DNA repair ability were observed. The presence of serum proteins did not influence O-ION toxicity. Iron ions released from the O-ION surface seemed not to be responsible for the cytotoxic and genotoxic effects observed. Environ. Mol. Mutagen. 2019. © 2019 Wiley Periodicals, Inc.
Keywords:iron oxide nanoparticles  A172 cells  neurotoxicity  cytotoxicity  genotoxicity
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