title: The role of reactive oxygen species in the genotoxicity of surface-modified magnetite nanoparticles.
abstract: The generation of reactive oxygen species (ROS) has been proposed as the underlying mechanism involved in the genotoxicity of iron oxide nanoparticles. The data published to date are, however, inconsistent, and the mechanism underlying ROS formation has not been completely elucidated. Here, we investigated the capacity of several surface-modified magnetite nanoparticles (MNPs) to generate ROS in A549 human lung adenocarcinoma epithelial cells and HEL 12469 human embryonic lung fibroblasts. All MNPs, regardless of the coating, induced significant levels of DNA breakage in A549 cells but not in HEL 12469 cells. Under the same treatment conditions, variable low levels of intracellular ROS were detected in both A549 and HEL 12469 cells, but compared with control treatment, none of the coated MNPs produced any significant increase in oxidative damage to DNA in either of these cell lines. Indeed, no significant changes in the total antioxidant capacity and intracellular glutathione levels were observed in MNPs-treated human lung cell lines regardless of surface coating. In line with these results, none of the surface-modified MNPs increased significantly the GPx activity in A549 cells and the SOD activity in HEL 12469 cells. The GPx activity was significantly increased only in SO-Fe3O4-treated HEL 12469 cells. The SOD activity was significantly increased in SO-PEG-PLGA-Fe3O4-treated A549 cells but significantly decreased in SO-Fe3O4-treated A549 cells. Our data indicate that oxidative stress plays, at most, only a marginal role in the genotoxicity of surface-modified MNPs considered in this study in human lung cells.
authors.affiliation: Cancer Research Institute, SAS, Vlárska 7, 833 91 Bratislava, Slovakia.
authors.forename: Monika
authors.initials: M
authors.lastname: Mesárošová
authors.affiliation: Cancer Research Institute, SAS, Vlárska 7, 833 91 Bratislava, Slovakia.
authors.forename: Katarína
authors.initials: K
authors.lastname: Kozics
authors.affiliation: Cancer Research Institute, SAS, Vlárska 7, 833 91 Bratislava, Slovakia.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bábelová
authors.affiliation: Cancer Research Institute, SAS, Vlárska 7, 833 91 Bratislava, Slovakia.
authors.forename: Eva
authors.initials: E
authors.lastname: Regendová
authors.affiliation: Cancer Research Institute, SAS, Vlárska 7, 833 91 Bratislava, Slovakia.
authors.forename: Michal
authors.initials: M
authors.lastname: Pastorek
authors.affiliation: Polymer Institute, SAS, Dúbravská cesta 9, 845 41 Bratislava, Slovakia.
authors.forename: Dominika
authors.initials: D
authors.lastname: Vnuková
authors.affiliation: Cancer Research Institute, SAS, Vlárska 7, 833 91 Bratislava, Slovakia.
authors.forename: Barbora
authors.initials: B
authors.lastname: Buliaková
authors.affiliation: Polymer Institute, SAS, Dúbravská cesta 9, 845 41 Bratislava, Slovakia.
authors.forename: Filip
authors.initials: F
authors.lastname: Rázga
authors.affiliation: Cancer Research Institute, SAS, Vlárska 7, 833 91 Bratislava, Slovakia. Electronic address: alena.gabelova@savba.sk.
authors.forename: Alena
authors.initials: A
authors.lastname: Gábelová
mesh_terms: D017209:Apoptosis; D002478:Cells, Cultured; D004249:DNA Damage; D005978:Glutathione / Q000032:analysis; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D058185:Magnetite Nanoparticles / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D058185:Magnetite Nanoparticles; D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione
keywords: Antioxidant enzymes; Human lung cells; Magnetite nanoparticles; Oxidative DNA damage; Reactive oxygen species