Towards a New Paradigm in Nano-Genotoxicology: Facing Complexity of Nanomaterials' Cellular Interactions and Effects.
Changes in paradigm contribute to advances in research. The current paradigms for the evaluation of toxicity of chemicals refer to linear or curvilinear dose-response curves with or without threshold and to surface-dependent induction of oxidative damage for particles. The unique physicochemical properties and biological/genotoxic activity of engineered nanomaterials (NMs) require the development of a new paradigm. Because of their unusual dosimetry and their multiple interactions at NM level (agglomeration/aggregation) and at different cellular and extracellular levels, NMs are likely to have complex modes of action (multiple hits at multiple targets) leading to complex thresholded-non-thresholded dose-response curves. Understanding their cellular targets and their modes of action will contribute to the production of safe-by-design NMs. An integrative, cell-by-cell approach for genotoxic effects should be applied to tackle this emerging paradigm in nano-genotoxicology.
Laboratory of Cell Genetics, Free University of Brussels (VUB), Brussels, Belgium.
Laetitia
L
Gonzalez
Institute for Molecular Biology and Pathology, CNR, Rome, Italy.
Enrico
E
Cundari
Laboratory of Cell Genetics, Free University of Brussels (VUB), Brussels, Belgium.
Luc
L
Leyns
Laboratory of Cell Genetics, Free University of Brussels (VUB), Brussels, Belgium.
Micheline
M
Kirsch-Volders
D002450:Cell Communication; D004249:DNA Damage; D006801:Humans; D009152:Mutagenicity Tests / Q000379:methods; D049329:Nanostructures / Q000633:toxicity*; D009369:Neoplasms / Q000209:etiology / Q000235:genetics; D010316:Particle Size; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000633:toxicity*; D013499:Surface Properties
D017382:Reactive Oxygen Species