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- Karlsson, Hanna L., et al.
(författare)
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Mechanism-based genotoxicity screening of metal oxide nanoparticles using the ToxTracker panel of reporter cell lines
- 2014
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Ingår i: Particle and Fibre Toxicology. - : Springer Science and Business Media LLC. - 1743-8977. ; 11, s. 41-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The rapid expansion of manufacturing and use of nano-sized materials fuels the demand for fast and reliable assays to identify their potential hazardous properties and underlying mechanisms. The ToxTracker assay is a recently developed mechanism-based reporter assay based on mouse embryonic stem (mES) cells that uses GFP-tagged biomarkers for detection of DNA damage, oxidative stress and general cellular stress upon exposure. Here, we evaluated the ability of the ToxTracker assay to identify the hazardous properties and underlying mechanisms of a panel of metal oxide-and silver nanoparticles (NPs) as well as additional non-metallic materials (diesel, carbon nanotubes and quartz). Methods: The metal oxide-and silver nanoparticles were characterized in terms of agglomeration and ion release in cell medium (using photon cross correlation spectroscopy and inductively coupled plasma with optical emission spectroscopy, respectively) as well as acellular ROS production (DCFH-DA assay). Cellular uptake was investigated by means of transmission electron microscopy. GFP reporter induction and cytotoxicity of the NPs was simultaneously determined using flow cytometry, and genotoxicity was further tested using conventional assays (comet assay, gamma-H(2)AX and RAD51 foci formation). Results: We show that the reporter cells were able to take up nanoparticles and, furthermore, that exposure to CuO, NiO and ZnO nanoparticles as well as to quartz resulted in activation of the oxidative stress reporter, although only at high cytotoxicity for ZnO. NiO NPs activated additionally a p53-associated cellular stress response, indicating additional reactive properties. Conventional assays for genotoxicity assessment confirmed the response observed in the ToxTracker assay. We show for CuO NPs that the induction of oxidative stress is likely the consequence of released Cu ions whereas the effect by NiO was related to the particles per se. The DNA replication stress-induced reporter, which is most strongly associated with carcinogenicity, was not activated by any of the tested nanoparticles. Conclusions: We conclude that the ToxTracker reporter system can be used as a rapid mechanism-based tool for the identification of hazardous properties of metal oxide NPs. Furthermore, genotoxicity of metal oxide NPs seems to occur mainly via oxidative stress rather than direct DNA binding with subsequent replication stress.
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| 2. |
- Rivera-Ferre, Marta G., et al.
(författare)
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A vision for transdisciplinarity in Future Earth : Perspectives from young researchers
- 2013
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Ingår i: The Journal of Agriculture, Food Systems, and Community Development. - : New Leaf Associates, Inc.. - 2152-0798 .- 2152-0801. ; 3:4, s. 249-260
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Tidskriftsartikel (refereegranskat)abstract
- Meeting the demand for food, energy, and water as world population increases is a major goal for the food systems of the future. These future challenges, which are complex, multiscalar, and cross-sectoral in nature, require a food systems approach that recognizes the socio-ecological and socio-technical dimensions of food (Ericksen, 2008; Ingram, 2011; Rivera-Ferre, 2012). The United Nations' Future Earth Program aims to provide a new platform for consolidating the knowledge required for societies to transition to global sustainability (Future Earth Transition Team, 2012). In this paper, we explore how Future Earth could become a vehicle for inspiring the production of new research ideas and collaborations for sustainably transforming the future food system. We do this on the basis of a synthesis of views from 28 young (below 40 years old) food system scientists, representing five continents. Their expertise comes from disciplines including food engineering, agronomy, ecology, geography, psychology, public health, food politics, nutritional science, political science, sociology and sustainability science. This paper begins with an outline of the institutional framework of Future Earth and how it might support innovative transdisciplinary research on food systems, and the position of young scientists within this framework. Secondly, we outline the key insights expressed by the young scientists during the Food Futures Conference in Villa Vigoni, Italy, in April 2013, including the core research questions raised during the meeting as well as some of the challenges involved in realizing their research ambitions within their professional spheres.
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