Investigation of the genetic toxicity by dextran-coated superparamagnetic iron oxide nanoparticles (SPION) in HepG2 cells using the comet assay and cytokinesis-block micronucleus assay

Abstract

Dextran-coated superparamagnetic iron oxide nanoparticles (dextran-SPION) have been commercially used for medical applications, such as magnetic imaging or targeted drug delivery, etc. Despite of this usefulness, there are continuous controversies on safety/toxicity of various SPIONs. In the case of dextran-SPION, the reported adverse effects include the cytotoxicity, oxidative stress and DNA damage in many cell types. In this study, the genetic toxicity of dextran-SPION in human hepatoma (HepG2) cells was evaluated with comet assay and cytokinesis-block micronucleus (CBMN) assay. Dextran-SPION did not inhibit cell proliferation as a function of dose and time. The comet assay indicated that 5 μg/mL of dextran-SPION induced a significant DNA strand breaks. A dose-dependent increase of the micronucleus (MN) frequency was observed in CBMN assay. The formation of intracellular reactive oxygen species (ROS) in HepG2 cells was induced by dextran-SPION. The results demonstrated that dextran-SPION exerted genetic toxicity in HepG2 cells. Also, it suggests that a mechanism by which dextran-SPION triggers the DNA and chromosomal damage in HepG2 cells may be via the generation of intracellular ROS.