Toxicity of (nano)particles with a focus on genome instability
The general public and workers in occupational settings are frequently exposed to elevated levels of airborne particles. Furthermore, the introduction of nanotechnology in society has led to an increased likelihood of exposure to nanoparticles (particles smaller than 100 nm) for workers and consumers. This research project is focused on understanding lung cell toxicity and underlying mechanisms following lung exposure to metal-containing particles. We investigate which particle characteristics that are of most importance for the various toxic effects observed, such as the particle size and release of metal ions. In particular, we focus on investigating effects linked to genome instability and cancer such as the ability of particles to cause genotoxicity, oxidative stress, epigenetic alterations and cell transformation. These effects are mainly studied using in vitro cultures of human lung cells as well as reporter cell lines based on mouse embryonic stem cells. A further aim with the research is to develop and use in vitro methods that better resembles the real exposure situation in the lung. This includes e.g. to expose lung cells to an aerosol of particles in the “air-liquid interface” as well as using long term (weeks) cellular exposures and co-cultures.
These projects are important for hazard identification and risk assessment of (nano)particles with the overall goal to prevent negative health, particularly cancer, as a consequence of exposure to (nano)particles.
- FORTE - The Swedish Research Council for Health, Working Life and Welfare
- VR- The Swedish Research Council
- Karolinska Institutet
- FP-7 NANoREG
Can the comet assay be used reliably to detect nanoparticle-induced genotoxicity?
Karlsson HL, Di Bucchianico S, Collins AR, Dusinska M
Environ. Mol. Mutagen. 2015 Mar;56(2):82-96
Mechanism-based genotoxicity screening of metal oxide nanoparticles using the ToxTracker panel of reporter cell lines.
Karlsson HL, Gliga AR, Calléja FM, Gonçalves CS, Wallinder IO, Vrieling H, et al
Part Fibre Toxicol 2014 Sep;11():41
Size-dependent cytotoxicity of silver nanoparticles in human lung cells: the role of cellular uptake, agglomeration and Ag release.
Gliga AR, Skoglund S, Wallinder IO, Fadeel B, Karlsson HL
Part Fibre Toxicol 2014 Feb;11():11
Cell membrane damage and protein interaction induced by copper containing nanoparticles--importance of the metal release process.
Karlsson HL, Cronholm P, Hedberg Y, Tornberg M, De Battice L, Svedhem S, et al
Toxicology 2013 Nov;313(1):59-69
Cellular dose of partly soluble Cu particle aerosols at the air-liquid interface using an in vitro lung cell exposure system.
Elihn K, Cronholm P, Karlsson HL, Midander K, Odnevall Wallinder I, Möller L
J Aerosol Med Pulm Drug Deliv 2013 Apr;26(2):84-93
Size-dependent toxicity of metal oxide particles--a comparison between nano- and micrometer size.
Karlsson HL, Gustafsson J, Cronholm P, Möller L
Toxicol. Lett. 2009 Jul;188(2):112-8
Copper oxide nanoparticles are highly toxic: a comparison between metal oxide nanoparticles and carbon nanotubes.
Karlsson HL, Cronholm P, Gustafsson J, Möller L
Chem. Res. Toxicol. 2008 Sep;21(9):1726-32
Reporter cell lines: http://toxys.com/
Air liquid interface exposure: http://www.inhalation.se/
FP-7 NANoREG: http://nanoreg.eu/