title: Cytotoxicity and morphological transforming potential of cobalt nanoparticles, microparticles and ions in Balb/3T3 mouse fibroblasts: an in vitro model.
abstract: We previously described the behaviour of different cobalt forms, i.e., cobalt nanoparticles (CoNP), cobalt microparticles (CoMP) and cobalt ions (Co(2+)), in culture medium (dissolution, interaction with medium components, bioavailability) as well as their uptake and intracellular distribution in Balb/3T3 mouse fibroblasts (Sabbioni, Nanotoxicology, 2012). Here, we assess the cytotoxicity and morphological transformation of CoNP compared not only to Co(2+), but also to CoMP and to released Co products. Cytotoxicity reached maximum at 4-h exposure, with ranking CoMP > CoNP > Co(2+). However, if we consider toxicity as a function of intracellular Co, toxicity of the ionic forms seems to prevail over the particles. Co forms other than Co(2+) released from particles had toxicity intermediate between particles and ions. Alterations in concentrations of essential elements (Cu, Mg, Zn) in cells exposed to Co particles may contribute to toxicity. Both CoMP and CoNP (but not Co(2+) and other released Co forms) induced morphological transformation (CoMP > CoNP). This was dependent on reactive oxygen species production and lipid peroxidation, as indicated by inhibition of type III foci with ascorbic acid. The present results suggest that the previously demonstrated massive mitochondrial and nuclear Co internalisation and DNA adduct formation by CoMP and CoNP (Sabbioni, Nanotoxicology, 2012) induce toxicity and transformation. On the contrary, the role of ions released by particles in culture medium is negligible. Thus, both the chemical and the physical properties of Co particles contribute to cytotoxicity and morphological transformation.
authors.affiliation: Ecsin - European Center for the Sustainable Impact of Nanotechnologies, Veneto Nanotech SCpA , Rovigo , Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Sabbioni
authors.forename: Salvador
authors.initials: S
authors.lastname: Fortaner
authors.forename: Massimo
authors.initials: M
authors.lastname: Farina
authors.forename: Riccardo
authors.initials: R
authors.lastname: Del Torchio
authors.forename: Iolanda
authors.initials: I
authors.lastname: Olivato
authors.forename: Claudia
authors.initials: C
authors.lastname: Petrarca
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bernardini
authors.forename: Renato
authors.initials: R
authors.lastname: Mariani-Costantini
authors.forename: Silvia
authors.initials: S
authors.lastname: Perconti
authors.forename: Luca
authors.initials: L
authors.lastname: Di Giampaolo
authors.forename: Rosalba
authors.initials: R
authors.lastname: Gornati
authors.forename: Mario
authors.initials: M
authors.lastname: Di Gioacchino
mesh_terms: D000818:Animals; D041702:BALB 3T3 Cells; D002470:Cell Survival / Q000187:drug effects*; D003035:Cobalt / Q000633:toxicity*; D005347:Fibroblasts / Q000187:drug effects; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D008863:Microspheres; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D003035:Cobalt