caa a22 4500 44585300X CHVBK 20180317145419.0 cr unu---uuuuu 170323e20110701xx s 000 0 eng 10.1007/s00204-010-0545-5 doi (NATIONALLICENCE)springer-10.1007/s00204-010-0545-5 Cytotoxicity and genotoxicity of silver nanoparticles in the human lung cancer cell line, A549 [Elektronische Daten] [Rasmus Foldbjerg, Duy Dang, Herman Autrup] Nanomaterials, especially silver nanoparticles (Ag NPs), are used in a rapidly increasing number of commercial products. Accordingly, the hazards associated with human exposure to nanomaterials should be investigated to facilitate the risk assessment process. A potential route of exposure to NPs is through the respiratory system. In the present study, we investigated the effects of well-characterized PVP-coated Ag NPs and silver ions (Ag+) in the human, alveolar cell line, A549. Dose-dependent cellular toxicity caused by Ag NPs and Ag+ was demonstrated by the MTT and annexin V/propidium iodide assays, and evidence of Ag NP uptake could be measured indirectly by atomic absorption spectroscopy and flow cytometry. The cytotoxicity of both silver compounds was greatly decreased by pretreatment with the antioxidant, N-acetyl-cysteine, and a strong correlation between the levels of reactive oxygen species (ROS) and mitochondrial damage (r s=−0.8810; p=0.0039) or early apoptosis (r s=0.8857; p=0.0188) was observed. DNA damage induced by ROS was detected as an increase in bulky DNA adducts by 32P postlabeling after Ag NP exposure. The level of bulky DNA adducts was strongly correlated with the cellular ROS levels (r s=0.8810, p=0.0039) and could be inhibited by antioxidant pretreatment, suggesting Ag NPs as a mediator of ROS-induced genotoxicity. Springer-Verlag, 2010 Silver nationallicence Nanoparticles nationallicence Reactive oxygen species nationallicence Apoptosis nationallicence Bulky DNA adducts nationallicence Foldbjerg Rasmus Nanoparticle Safety Group, Department of Environmental and Occupational Medicine, Institute of Public Health, Aarhus University, Bartholins Allé 2, Building 1260, 8000, Aarhus, Denmark aut Dang Duy Nanoparticle Safety Group, Department of Environmental and Occupational Medicine, Institute of Public Health, Aarhus University, Bartholins Allé 2, Building 1260, 8000, Aarhus, Denmark aut Autrup Herman Nanoparticle Safety Group, Department of Environmental and Occupational Medicine, Institute of Public Health, Aarhus University, Bartholins Allé 2, Building 1260, 8000, Aarhus, Denmark aut Archives of Toxicology Springer-Verlag 85/7(2011-07-01), 743-750 0340-5761 85:7<743 2011 85 204 https://doi.org/10.1007/s00204-010-0545-5 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-010-0545-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Foldbjerg Rasmus Nanoparticle Safety Group, Department of Environmental and Occupational Medicine, Institute of Public Health, Aarhus University, Bartholins Allé 2, Building 1260, 8000, Aarhus, Denmark aut NATIONALLICENCE 700 1- Dang Duy Nanoparticle Safety Group, Department of Environmental and Occupational Medicine, Institute of Public Health, Aarhus University, Bartholins Allé 2, Building 1260, 8000, Aarhus, Denmark aut NATIONALLICENCE 700 1- Autrup Herman Nanoparticle Safety Group, Department of Environmental and Occupational Medicine, Institute of Public Health, Aarhus University, Bartholins Allé 2, Building 1260, 8000, Aarhus, Denmark aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/7(2011-07-01), 743-750 0340-5761 85:7<743 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer