| Autor: |
Toprani SM; John B. Little Center of Radiation Sciences, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, United States., Bitounis D; Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, Harvard T.H. Chan School of Public Health, 655 Huntington Avenue, Boston, Massachusetts 02115, United States., Huang Q; Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, Harvard T.H. Chan School of Public Health, 655 Huntington Avenue, Boston, Massachusetts 02115, United States.; Center for Excellence in Regional Atmospheric Environment, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China., Oliveira N; Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, Harvard T.H. Chan School of Public Health, 655 Huntington Avenue, Boston, Massachusetts 02115, United States., Ng KW; Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, Harvard T.H. Chan School of Public Health, 655 Huntington Avenue, Boston, Massachusetts 02115, United States.; School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore.; Environmental Chemistry and Materials Centre, Nanyang Environment and Water Research Institution, 1 Cleantech Loop, CleanTech One, Singapore 637141, Singapore., Tay CY; School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore.; School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore., Nagel ZD; John B. Little Center of Radiation Sciences, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, United States., Demokritou P; Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, Harvard T.H. Chan School of Public Health, 655 Huntington Avenue, Boston, Massachusetts 02115, United States. |
| Abstrakt: |
The potential genotoxic effects of engineered nanomaterials (ENMs) may occur through the induction of DNA damage or the disruption of DNA repair processes. Inefficient DNA repair may lead to the accumulation of DNA lesions and has been linked to various diseases, including cancer. Most studies so far have focused on understanding the nanogenotoxicity of ENM-induced damages to DNA, whereas the effects on DNA repair have been widely overlooked. The recently developed fluorescence multiplex-host-cell reactivation (FM-HCR) assay allows for the direct quantification of multiple DNA repair pathways in living cells and offers a great opportunity to address this methodological gap. Herein an FM-HCR-based method is developed to screen the impact of ENMs on six major DNA repair pathways using suspended or adherent cells. The sensitivity and efficiency of this DNA repair screening method were demonstrated in case studies using primary human small airway epithelial cells and TK6 cells exposed to various model ENMs (CuO, ZnO, and Ga 2 O 3 ) at subcytotoxic doses. It was shown that ENMs may inhibit nucleotide-excision repair, base-excision repair, and the repair of oxidative damage by DNA glycosylases in TK6 cells, even in the absence of significant genomic DNA damage. It is of note that the DNA repair capacity was increased by some ENMs, whereas it was suppressed by others. Overall, this method can be part of a multitier, in vitro hazard assessment of ENMs as a functional, high-throughput platform that provides insights into the interplay of the properties of ENMs, the DNA repair efficiency, and the genomic stability. |
