Advisor(s)
Abstract(s)
Superparamagnetic iron oxide nanoparticles (ION) have a wide range of potential
applications. Among them, the most important uses in biology and medicine are
as contrast agents in magnetic resonance imaging, as carriers for drug delivery or
transfection and as therapeutic agents in cancer therapy by magnetic field-mediated
hyperthermia. For all these applications, ION must be introduced in the human
body and come into contact with cells and tissues, so it is imperative to know the
potential risks associated to this exposure. Nevertheless, although ION biocompatibility
has been reported to be high, there is a lack of information regarding their
genotoxic potential, especially on the nervous system. Thus, the main objective
of this work was to examine possible genotoxic effects of ION (crystalline phase
magnetite, covered by oleic acid) on human SHSY5Y neuronal cells by the standard
alkaline comet assay, along with its OGG1 enzyme modified version to analyse oxidative
DNA damage. Previously we evaluated the possible interference of the ION
with the comet assay methodology and with OGG1 enzyme activity. ION were dispersed
both in complete and serum-free cell culture media, and cells were exposed
to four concentrations in the range 10-200 µg/ml for 3 and 24 h. Results obtained
showed increases in DNA damage, both primary and oxidative, after treatment with
oleic acid-coated ION, even though the highest concentrations were found to interfere
with OGG1 enzyme activity in incomplete cell culture medium. The results
of this study encourage the need for checking the suitability of comet assay when
used for testing genotoxicity of nanomaterials. Further investigations are required
to assess the ability of ION to induce oxidative stress, and to elucidate the specific
mechanism involved in primary DNA damage induced by these ION.
Description
Keywords
Comet Assay DNA Damage Magnetite Nanoparticles Neurotoxicity Oxidative Damage Nanoparticles Iron Oxide ION Genotoxicidade Ambiental
