Mechanistic insight into reactivity and (geno)toxicity of well-characterized nanoparticles of cobalt metal and oxides

Abstract

An increasing use of cobalt (Co)-based nanoparticles (NPs) in different applications and exposures at occupational settings triggers the need for toxicity assessment. Improved understanding regarding the physiochemical characteristics of Co metal NPs and different oxides in combination with assessment of toxicity and mechanisms may facilitate decisions for grouping during risk assessment. The aim of this study was to gain mechanistic insights in the correlation between NP reactivity and toxicity of three different Co-based NPs (Co, CoO, and CoO) by using various tools for characterization, traditional toxicity assays, as well as six reporter cell lines (ToxTracker) for rapid detection of signaling pathways of relevance for carcinogenicity. The results showed cellular uptake of all NPs in lung cells and induction of DNA strand breaks and oxidative damage (comet assay) by Co and CoO NPs. In-depth studies on the ROS generation showed high reactivity of Co, lower for CoO, and no reactivity of CoO NPs. The reactivity depended on the corrosion and transformation/dissolution properties of the particles and the media highlighting the role of the surface oxide and metal speciation as also confirmed by in silico modeling. By using ToxTracker, Co NPs were shown to be highly cytotoxic and induced reporters related to oxidative stress (Nrf2 signaling) and DNA strand breaks. Similar effects were observed for CoO NPs but at higher concentrations, whereas the CoO NPs were inactive at all concentrations tested. In conclusion, our study suggests that Co and CoO NPs, but not CoO, may be grouped together for risk assessment.

ToxTracker Reporter Cell Lines as a Tool for Mechanism-Based (Geno)Toxicity Screening of Nanoparticles—Metals, Oxides and Quantum Dots

“…Of the NPs tested, Mn and Mn 3 O 4 NPs caused by far the largest activation of the Srxn1-GFP reporter resulting in around 20-fold maximum increase compared with control ( Figure 4). The Sn, Sb 2 O 3 and Sb NPs were also active, inducing approximately a 7-10 fold increase (Figure 4), which is comparable to previous observations for Ni and NiO NPs [11], and for Co and CoO NPs [12]. Some induction (2.5 and 2.7-fold) was also observed for the V 2 O 5 and Ag NPs, respectively (Figure 4 and Supplementary Table S1).…”

“…Furthermore, Cr 2 O 3 caused a weak activation of one of the oxidative stress reporters (Srxn-1) and one of the DNA damage reporters (Rtkn). The absence of activation of any of the GFP-reporters has previously been observed in response to other NPs including TiO 2 , Fe 3 O 4 and Co 3 O 4 [10,12].…”

Chromium(III), chromium(VI) and cobalt release from leathers produced in Nicaragua

“…With the extraction conditions of this study, which is optimized for the detection of Cr(VI), Co is not stable in solution and is expected to precipitate in the form of Co phosphate . Nevertheless, Co was clearly detected, especially for leathers from one of the tanneries.…”

Recovery Ability of Human Adipose Stem Cells Exposed to Cobalt Nanoparticles: Outcome of Dissolution

“…Co ions are involved in several cellular processes, for example, in the induction of hypoxia by the increase in the inducible HIF-1α, which, in turn, could be the cause of reduced cell proliferation [31]. Some authors [32,33] reported that at a concentration of 100 μM, like used in our experiments, Co ions may induce reactive oxygen specie synthesis, which is responsible for DNA damage that, in turn, can alter the synthesis and the activity of many signaling proteins involved in the stress response, such as cell proliferation and apoptosis induction. qPCR experiments did not reveal any important involvement in mRNA expression of those genes susceptible to metal exposure and implicated in general (HSP70, MT2A) or in specific cell processes (SDHB1, MLL, CAS3, IQSEC1).…”