ToxTracker, the future for genotoxicity screening of nanoparticles
Many of the traditional genotoxicity test methods [e.g. unscheduled DNA synthesis assay, bacterial reverse mutation (Ames) test, etc.,] for determining the DNA damaging potential of chemical and biological compounds are not suitable for the evaluation of engineered nanomaterials (ENMs), due to a variety of methodological issues ranging from potential assay interferences to problems centered on low sample throughput. We previously published, in collaboration with the Karolinska Institute in Sweden, that ToxTracker is highly suitable to assess the genotoxicity hazards of various types of nanomaterials (Karlsson et al., 2014). Please read the latest publication in Mutagenesis: “emerging metrology for high-throughput nanomaterial genotoxicology”, an extensive review on the ToxTracker assay and other novel technologies for genotoxicity testing of nanoparticles.
Conclusion from the article:
“There are several advantages with using the ToxTracker assay in ENM genotoxicity studies. The mES cells that are used in the ToxTracker assay are untransformed, proficient in all major DNA damage and cellular stress response pathways and have been shown to efficiently engulf ENMs. The assay has shown good sensitivity and specificity for detecting genotoxic compounds when evaluated using a wide range of genotoxic and non-genotoxic chemicals. The ENMs tested so far have shown various effects, some being highly toxic and efficiently inducing one or several of the reporters and others showing no effects at all. In all, this indicates that the ToxTracker reporter cell assay can be applied as a rapid mechanism-based tool for assessing the potential genotoxic effects of ENMs. The assay is adapted to a 96-well plate format thus enabling medium/high-throughput screening. As for all assays relying on fluorescence, possible assay-interactions may be found for fluorescent ENMs, but this can easily be tested for by using the mES cells without the reporter gene. Another possible limitation could be dark ENMs that may scatter the fluorescence. For most ENMs, however, an interaction that substantially may influence the results appears unlikely at this point. Since the method is rapid and no processing of the cells (DNA extraction, etc.) is needed, it seems plausible that no assay-interactions occur for most ENMs. In conclusion, the ToxTracker reporter assay seems to be very promising for rapidly assessing the genotoxicity potential of ENMs”.
