Evaluation of cytotoxicity and genotoxicity induced by oleic acid-coated iron oxide nanoparticles in human astrocytes

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. Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia. Grant Number: ED481B 2016/190‐0 Fundação para a Ciência e a Tecnologia. Grant Number: SFRH/BD101060/2014 Deputación Provincial da Coruña. Grant Number: 2019000011550 Ministerio de Educación, Cultura y Deporte. Grant Number: PRX19/00353 Xunta de Galicia. Grant Number: ED431B 2019/02 This work was funded by Xunta de Galicia (ED431B 2019/02). Vanessa Valdiglesias was supported by a Xunta de Galicia postdoctoral fellowship (ED481B 2016/190-0), B. Laffon by a Ministerio de Educación, Cultura y Deporte fellowship (PRX19/00353), Natalia Fernández-Bertólez by a Deputación Provincial da Coruña fellowship (2019000011550), and Fátima Brandao by the Portuguese Foundation for Science and Technology (SFRH/BD101060/2014). Authors would also like to acknowledge COST Action CA15132 “The comet assay as a human biomonitoring tool (hCOMET).” info:eu-repo/semantics/publishedVersion