Abstract
The increased use of nanoparticles (NPs) requires efficient testing of their potential toxic effects. A promising approach is to use reporter cell lines to quickly assess the activation of cellular stress response pathways. This study aimed to use the ToxTracker reporter cell lines to investigate (geno)toxicity of various metal- or metal oxide NPs and draw general conclusions on NP-induced effects, in combination with our previous findings. The NPs tested in this study (n = 18) also included quantum dots (QDs) in different sizes. The results showed a large variation in cytotoxicity of the NPs tested. Furthermore, whereas many induced oxidative stress only few activated reporters related to DNA damage. NPs of manganese (Mn and Mn3O4) induced the most remarkable ToxTracker response with activation of reporters for oxidative stress, DNA damage, protein unfolding and p53-related stress. The QDs (CdTe) were highly toxic showing clearly size-dependent effects and calculations suggest surface area as the most relevant dose metric. Of all NPs investigated in this and previous studies the following induce the DNA damage reporter; CuO, Co, CoO, CdTe QDs, Mn, Mn3O4, V2O5, and welding NPs. We suggest that these NPs are of particular concern when considering genotoxicity induced by metal- and metal oxide NPs.
Highlights
The use of nanoparticles (NPs) is increasing worldwide in various applications, resulting in a need to more rapidly evaluate their potential toxicity
The ToxTracker reporter assay consists of a panel of six mouse embryonic stem cell lines that are modified with different green fluorescent protein (GFP) tagged reporters for various cellular signaling pathways involved in carcinogenesis [8,9]
Transmission electron microscopy (TEM) observations revealed a majority of the metal and metal oxide particles to be approximately spherical with primary sizes ranging from 10 to 250 nm, Figure 1 and Table 2
Summary
The use of nanoparticles (NPs) is increasing worldwide in various applications, resulting in a need to more rapidly evaluate their potential toxicity. The genotoxic potential is a crucial part in the risk and safety evaluation of NPs and currently this is most often evaluated by a battery of established methods including the comet assay and the micronucleus assay [1,2,3]. These methods are relatively time-consuming and there is a great demand for efficient and more high throughput assays for screening of the genotoxicity of NPs [4]. The ToxTracker reporter assay consists of a panel of six mouse embryonic stem (mES) cell lines that are modified with different green fluorescent protein (GFP) tagged reporters for various cellular signaling pathways involved in carcinogenesis [8,9]. We have shown the applicability of these reporters for various NPs including nickel-based [11], cobalt-based [12], and welding fume NPs [13]
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