title: Use of whole genome expression analysis in the toxicity screening of nanoparticles.
abstract: The use of nanoparticles (NPs) offers exciting new options in technical and medical applications provided they do not cause adverse cellular effects. Cellular effects of NPs depend on particle parameters and exposure conditions. In this study, whole genome expression arrays were employed to identify the influence of particle size, cytotoxicity, protein coating, and surface functionalization of polystyrene particles as model particles and for short carbon nanotubes (CNTs) as particles with potential interest in medical treatment. Another aim of the study was to find out whether screening by microarray would identify other or additional targets than commonly used cell-based assays for NP action. Whole genome expression analysis and assays for cell viability, interleukin secretion, oxidative stress, and apoptosis were employed. Similar to conventional assays, microarray data identified inflammation, oxidative stress, and apoptosis as affected by NP treatment. Application of lower particle doses and presence of protein decreased the total number of regulated genes but did not markedly influence the top regulated genes. Cellular effects of CNTs were small; only carboxyl-functionalized single-walled CNTs caused appreciable regulation of genes. It can be concluded that regulated functions correlated well with results in cell-based assays. Presence of protein mitigated cytotoxicity but did not cause a different pattern of regulated processes.
authors.affiliation: Center for Medical Research, Medical University of Graz, Stiftingtalstr. 24, 8010 Graz, Austria. Electronic address: eleonore.froehlich@medunigraz.at.
authors.forename: Eleonore
authors.initials: E
authors.lastname: Fröhlich
authors.affiliation: Center for Medical Research, Medical University of Graz, Stiftingtalstr. 24, 8010 Graz, Austria.
authors.forename: Claudia
authors.initials: C
authors.lastname: Meindl
authors.affiliation: Center for Medical Research, Medical University of Graz, Stiftingtalstr. 24, 8010 Graz, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Wagner
authors.affiliation: Center for Medical Research, Medical University of Graz, Stiftingtalstr. 24, 8010 Graz, Austria; Institute for Cell Biology, Histology and Embryology, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria.
authors.forename: Gerd
authors.initials: G
authors.lastname: Leitinger
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, Karl-Franzens-University of Graz, Universitätsplatz 1, 8010 Graz, Austria.
authors.forename: Eva
authors.initials: E
authors.lastname: Roblegg
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D053758:Nanoparticles / Q000633:toxicity*; D037742:Nanotubes, Carbon; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D011137:Polystyrenes / Q000633:toxicity
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D037742:Nanotubes, Carbon; D011137:Polystyrenes
keywords: Apoptosis; Cytotoxicity; Interleukin secretion; Nanotoxicology; Oxidative stress; Whole genome expression analysis
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