New Publication: Cellular uptake and genotoxic potential of industrial relevant nanomaterials in vitro

Evaluating the potential genotoxicity of nanomaterials (NMs) presents a unique challenge when using cell-based models. In addition to the requirement for physicochemical characterization of the test article, a negative genotoxicity test result is only trusted if the material has access to internal cellular components (evidence of uptake).  Evans and colleagues evaluated 10 NMs with different physicochemical properties that are used across food, medicine, and automotive industries. The new approach method ToxTracker was applied to evaluate genotoxicity with cellular uptake confirmed for 5 of the 10 NMs via transmission electron microscopy (TEM).

History of nano-Genotoxicity Testing

In 2018 an expert working group of genetic toxicologists met to discuss practical aspects of assessing NMs using existing genotoxicity tools.¹ After a critical review of existing literature, it was concluded that bacterial based assays were less informative than their in vitro mammalian counterparts, largely due to lack of cellular uptake and inability to inform on mode of action (MOA). Existing mammalian cell assays at the time also provided limited MOA information, which is significant as cytosolically stored nanomaterials may induce secondary genotoxicity via oxidative stress.² Hence, the use of ToxTracker, a murine stem cell GFP-reporter assay that can identify genotoxic MOA.

Nanomaterials were not genotoxic in ToxTracker

TEM identified cellular uptake for TiO2-NM105, silica, polystyrene, carbon black, and tungsten carbide (half of the NMs evaluated). The two other TiO2 NMs produced high degrees of side scatter during the ToxTracker analysis (via flow cytometry), which demonstrates that scatter properties alone do not indicate uptake of NMs. While there were increases in ER stress and oxidative stress for gold nanorods and tungsten carbide/cobalt, respectively, all NMs evaluated did not induce genotoxicity reporters in the ToxTracker assay.

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¹ Elespuru et al., 2018. Genotoxicity Assessment of Nanomaterials: Recommendations on Best Practices, Assays, and Methods, Toxicological Sciences;164(2), 391–416

² Horie & Tabei, 2021. Role of oxidative stress in nanoparticles toxicity. Free Radic Res;55(4):331-342.