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Inflammation and (secondary) genotoxicity of Ni and NiO nanoparticles
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Örebro University, School of Science and Technology. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID iD: 0000-0003-1132-7992
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2019 (English)In: Nanotoxicology, ISSN 1743-5390, E-ISSN 1743-5404Article in journal (Refereed) Epub ahead of print
Abstract [en]

Nanoparticle-induced genotoxicity can arise through different mechanisms, and generally, primary and secondary genotoxicity can be distinguished where the secondary is driven by an inflammatory response. It is, however, yet unclear how a secondary genotoxicity can be detected using in vitro methods. The aim of this study was to investigate inflammation and genotoxicity caused by agglomerated nickel (Ni) and nickel oxide (NiO) nanoparticles and, furthermore, to explore the possibility to test secondary (inflammation-driven) genotoxicity in vitro. As a benchmark particle to compare with, we used crystalline silica (quartz). A proteome profiler antibody array was used to screen for changes in release of 105 different cytokines and the results showed an increased secretion of various cytokines including vascular endothelial growth factor (VEGF) following exposure of macrophages (differentiated THP-1 cells). Both Ni and NiO caused DNA damage (comet assay) following exposure of human bronchial epithelial cells (HBEC) and interestingly conditioned media (CM) from exposed macrophages also resulted in DNA damage (2- and 3-fold increase for Ni and NiO, respectively). Similar results were also found when using a co-culture system of macrophages and epithelial cells. In conclusion, this study shows that it is possible to detect a secondary genotoxicity in lung epithelial cells by using in vitro methods based on conditioned media or co-cultures. Further investigation is needed in order to find out what factors that are causing this secondary genotoxicity and whether such effects are caused by numerous nanoparticles.

Place, publisher, year, edition, pages
Taylor & Francis, 2019.
Keywords [en]
Co-culture, nanoparticles, nanomaterials, nickel, secondary genotoxicity
National Category
Cell Biology
Identifiers
URN: urn:nbn:se:oru:diva-75726DOI: 10.1080/17435390.2019.1640908ISI: 000477282900001PubMedID: 31322448OAI: oai:DiVA.org:oru-75726DiVA, id: diva2:1342501
Funder
Swedish Research Council, 2014-4598Forte, Swedish Research Council for Health, Working Life and Welfare, 2011-0832
Note

Funding Agency:

Swedish Fund for Research Without Animal Experiments  2017-0041

Available from: 2019-08-13 Created: 2019-08-13 Last updated: 2019-08-13Bibliographically approved

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Alfaro-Moreno, Ernesto

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