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Despite the wide use of nanoscale materials in several industrial applications as well as in biology and medicine, very little research has been carried out on the potential toxicity of nanoparticles. We had previously obtained 10 differentially expressed mRNAs in BALB3T3 fibroblasts exposed to different forms of cobalt, i.e., microparticles, nanoparticles, and ions. Those genes represented candidate biomarkers for indicating specific cellular effects after cobalt nanoparticle exposure. In the present paper, we have further evaluated the expression of those genes by real-time RT-PCR after exposure to different forms of cobalt. Moreover, we also tested some genes associated with cobalt toxicity, such as VEGF, HIF-1α, and Bnip3. We identified biomarkers that are sensitive to cobalt ions that we think to be the reactive form. Our data, in fact, are consistent with the possibility that Co-nano, due to their large surface area, once inside the cell dissolve and act as ions. [ABSTRACT FROM AUTHOR]

The mechanistic understanding of nanotoxicity requires the physico-chemical characterisation of nanoparticles (NP), and their comparative investigation relative to the corresponding ions and microparticles (MP). Following this approach, the authors studied the dissolution, interaction with medium components, bioavailability in culture medium, uptake and intracellular distribution of radiolabelled Co forms (CoNP, CoMP and Co2+) in Balb/3T3 mouse fibroblasts. Co2+ first saturates the binding sites of molecules in the extracellular milieu (e.g., albumin and histidine) and on the cell surface. Only after saturation, Co2+ is actively uptaken. CoNP, instead, are predicted to be internalised by endocytosis. Dissolution of Co particles allows the formation of Co compounds (CoNP-rel), whose mechanism of cellular internalisation is unknown. Co uptake (ranking CoMP > CoNP > Co2+) reached maximum at 4 h. Once inside the cell, CoNP spread into the cytosol and organelles. Consequently, massive amounts of Co ions and CoNP-rel can reach subcellular compartments normally unexposed to Co2+. This could explain the fact that the nuclear and mitochondrial Co concentrations resulted significantly higher than those obtained with Co2+. [ABSTRACT FROM AUTHOR]

Nanogenotoxicology is an emergent area of research, relevant for estimating the potential carcinogenic risk of nanomaterials. Since most of the approaches use in vitro studies, and neglecting the whole organism limits the accuracy of the obtained results, we have used Drosophila melanogaster to study the possible genotoxic potential of cobalt nanoparticles (Co NPs). The wing somatic mutation and recombination test has been the test of choice. This test is based on the principle that the loss of heterozygosis and the corresponding expression of the suitable recessive markers, multiple wing hairs and flare-3 can lead to the formation of mutant clone cells in growing up larvae, which are expressed as mutant spots on the wings of adult flies. Co NPs, as well as the ionic form cobalt chloride, were given to third instar larvae through the food, at concentrations ranging from 0.1 to 10 mM. The results obtained indicate that both cobalt forms are able to induce significant increases in the frequency of mutant clones. Although at low concentrations only Co NPs were genotoxic, the level of genetic damage obtained at the highest dose tested of cobalt chloride (10 mM) showed a significant higher increase in the frequency of total spots than those observed after the treatment with cobalt nanoparticles. As conclusion, our results indicate that Co NPs were able to induce genotoxic activity in the wing-spot assay of D. melanogaster, mainly via the induction of somatic recombination. The differences observed in the behaviour of the two selected cobalt forms may result from differences in the uptake. [ABSTRACT FROM AUTHOR]

Due to difficulties in tracing engineered nanoparticles (ENPs) in complex media, there are few data on the exposure of soil biota to ENPs. This study used neutron activated cobalt (Co NPs) and silver (Ag NPs) nanoparticles, as well as soluble cobalt and silver salts, to assess the uptake, excretion and biodistribution in the earthworm Eisenia fetida. Concentrations of cobalt in worms after four weeks exposure reached 88% and 69% of the Co ions and Co NPs concentrations in food, respectively, while corresponding values for Ag ions and Ag NPs were 2.3% and 0.4%. Both Ag ions and Ag NPs in earthworms were excreted rapidly, while only 32% of the cobalt accumulated from Co ions and Co NPs were excreted within four months. High accumulation of cobalt was found in blood and in the digestive tract. Metal characterization in the exposure medium was assessed by sequential extraction and ultrafiltration. The Co NPs showed significant dissolution and release of ions, while Ag ions and particularly Ag NPs were more inert. [ABSTRACT FROM AUTHOR]