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

Environ Mol Mutagen. 2019 Dec;60(9):816-829. doi: 10.1002/em.22323. Epub 2019 Aug 30.

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: A172 cells; cytotoxicity; genotoxicity; iron oxide nanoparticles; neurotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Astrocytes / drug effects*
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chromosome Aberrations / drug effects
  • Comet Assay / methods
  • DNA Damage / drug effects
  • DNA Repair / drug effects
  • Ferric Compounds / adverse effects*
  • Humans
  • Metal Nanoparticles / adverse effects*
  • Micronucleus Tests / methods
  • Mutagenicity Tests / methods
  • Mutagens / adverse effects
  • Oleic Acid / adverse effects*

Substances

  • Ferric Compounds
  • Mutagens
  • ferric oxide
  • Oleic Acid