Overview on the Genotoxicity of Nanomaterials

Background/Aims: The evaluation of the genotoxic potential of engineered nanomaterials (ENMs) for a safer and sustainable production requires understanding of their mode of action (MoA) and adequate hazard/risk assessment. In a recent review (Gonzalez et al. 2008) we aimed (1) at providing an evaluation of in vitro and in vivo genotoxicity data available for ENM, (2) at proposing minimal criteria for conducting nano-genotoxicity assays and (3) at discussing their potential cellular targets
Results and conclusions: No definitive conclusion could be drawn as to their genotoxic activity, because of the limited number of data, incomplete physico-chemical characterization of ENMs examined and shortcomings in experimental approaches. The evaluation revealed gaps to be considered in future studies (e.g. one-sided approach focusing mainly on ROS as mode of action) and the need to develop adequate positive controls. We applied these criteria to amorphous silica nanoparticles (SNPs) of different sizes. The in vitro CBMN assay showed an induction of MN frequencies after treatment with 16 and 104 nm SNPs, with a higher fold induction after treatment with the smallest SNPs. The cellular dose, expressed as particle number or as surface area, is an adequate dose metric for determinants of MN induction. Besides oxidative damage (alkaline comet assay + fpg), these SNPs induced other genotoxic effects, such as chromosome loss, metaphase block and mitotic slippage, suggesting interference with the mitotic spindle. In conclusion, in future studies it is crucial to consider (1) appropriate metrics, (2) cellular uptake kinetics and (3) different possible mechanisms of ENM-induced genotoxicity.