Abstract
Increased engineered nanomaterial (ENM) production and incorporation in consumer and biomedical products has raised concerns about the potential adverse effects. The DNA damaging capacity is of particular importance since damaged genetic material can lead to carcinogenesis. Consequently, reliable and robust in vitro studies assessing ENM genotoxicity are of great value. We utilized two complementary assays based on different measurement principles: (1) comet assay and (2) FADU (fluorimetric detection of alkaline DNA unwinding) assay. Assessing cell viability ruled out false-positive results due to DNA fragmentation during cell death. Potential structure–activity relationships of 10 ENMs were investigated: three silica nanoparticles (SiO2-NP) with varying degrees of porosity, titanium dioxide (TiO2-NP), polystyrene (PS-NP), zinc oxide (ZnO-NP), gold (Au-NP), graphene oxide (GO) and two multi-walled carbon nanotubes (MWNT). SiO2-NPs, TiO2-NP and GO were neither cytotoxic nor genotoxic to Jurkat E6-I cells. Quantitative interference corrections derived from GO results can make the FADU assay a promising screening tool for a variety of ENMs. MWNT merely induced cytotoxicity, while dose- and time-dependent cytotoxicity of PS-NP was accompanied by DNA fragmentation. Hence, PS-NP served to benchmark threshold levels of cytotoxicity at which DNA fragmentation was expected. Considering all controls revealed the true genotoxicity for Au-NP and ZnO-NP at early time points.
Highlights
Due to their novel and unique physico-chemical properties, engineered nanomaterials (ENMs) are remarkable for their rapid technological development accompanied by increasing production in the last two decades
The evaluation of ENM genotoxicity in human cells is of great importance since genotoxic insults
There is only limited comparability and a great uncertainty regarding the genotoxic potential of various ENMs
Summary
Due to their novel and unique physico-chemical properties, engineered nanomaterials (ENMs) are remarkable for their rapid technological development accompanied by increasing production in the last two decades. Because of their small size, particulate shape, increased surface area and surface reactivity, some of these new nanosized materials might cause different biological effects compared to the bulk, composite or ionic form. The conflictive literature on ENM toxicity impedes their evaluation by regulatory bodies and hinders the efficient transfer of nano-based applications into the clinic. For these reasons, the toxicological impact of ENMs needs to be thoroughly investigated by in vitro and in vivo studies. The evaluation of ENM genotoxicity in human cells is of great importance since genotoxic insults
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