title: Carboxylated short single-walled carbon nanotubes but not plain and multi-walled short carbon nanotubes show in vitro genotoxicity.
abstract: Long carbon nanotubes (CNTs) resemble asbestos fibers due to their high length to diameter ratio and they thus have genotoxic effects. Another parameter that might explain their genotoxic effects is contamination with heavy metal ions. On the other hand, short (1-2 µm) CNTs do not resemble asbestos fibers, and, once purified from contaminations, they might be suitable for medical applications. To identify the role of fiber thickness and surface properties on genotoxicity, well-characterized short pristine and carboxylated single-walled (SCNTs) and multi-walled (MCNTs) CNTs of different diameters were studied for cytotoxicity, the cell's response to oxidative stress (immunoreactivity against hemoxygenase 1 and glutathione levels), and in a hypoxanthine guanine phosphoribosyltransferase (HPRT) assay using V79 chinese hamster fibroblasts and human lung adenocarcinoma A549 cells. DNA repair was demonstrated by measuring immunoreactivity against activated histone H2AX protein. The number of micronuclei as well as the number of multinucleated cells was determined. CNTs acted more cytotoxic in V79 than in A549 cells. Plain and carboxylated thin (<8 nm) SCNTs and MCNTs showed greater cytotoxic potential and carboxylated CNTs showed indication for generating oxidative stress. Multi-walled CNTs did not cause HPRT mutation, micronucleus formation, DNA damage, interference with cell division, and oxidative stress. Carboxylated, but not plain, SCNTs showed indication for in vitro DNA damage according to increase of H2AX-immunoreactive cells and HPRT mutation. Although short CNTs presented a low in vitro genotoxicity, functionalization of short SCNTs can render these particles genotoxic.
authors.affiliation: *Center for Medical Research, Medical University of Graz; Institute for Cell Biology, Histology and Embryology, Medical University of Graz; and Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, Karl-Franzens-University of Graz, 8010 Graz, Austria.
authors.forename: Maria
authors.initials: M
authors.lastname: Mrakovcic
authors.affiliation: *Center for Medical Research, Medical University of Graz; Institute for Cell Biology, Histology and Embryology, Medical University of Graz; and Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, Karl-Franzens-University of Graz, 8010 Graz, Austria.
authors.forename: Claudia
authors.initials: C
authors.lastname: Meindl
authors.affiliation: *Center for Medical Research, Medical University of Graz; Institute for Cell Biology, Histology and Embryology, Medical University of Graz; and Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, Karl-Franzens-University of Graz, 8010 Graz, Austria *Center for Medical Research, Medical University of Graz; Institute for Cell Biology, Histology and Embryology, Medical University of Graz; and Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, Karl-Franzens-University of Graz, 8010 Graz, Austria.
authors.forename: Gerd
authors.initials: G
authors.lastname: Leitinger
authors.affiliation: *Center for Medical Research, Medical University of Graz; Institute for Cell Biology, Histology and Embryology, Medical University of Graz; and Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, Karl-Franzens-University of Graz, 8010 Graz, Austria.
authors.forename: Eva
authors.initials: E
authors.lastname: Roblegg
authors.affiliation: *Center for Medical Research, Medical University of Graz; Institute for Cell Biology, Histology and Embryology, Medical University of Graz; and Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, Karl-Franzens-University of Graz, 8010 Graz, Austria eleonore.froehlich@medunigraz.at.
authors.forename: Eleonore
authors.initials: E
authors.lastname: Fröhlich
mesh_terms: D000818:Animals; D002264:Carboxylic Acids / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006657:Histones / Q000378:metabolism; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D009154:Mutation; D037742:Nanotubes, Carbon / Q000633:toxicity*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D010316:Particle Size; D018570:Risk Assessment; D013499:Surface Properties
chemical_list: D002264:Carboxylic Acids; D006657:Histones; D037742:Nanotubes, Carbon; C077020:histone H2A.F-Z; D007041:Hypoxanthine Phosphoribosyltransferase
keywords: HPRT mutation assay; carbon nanotubes; cytotoxicity; genotoxicity; micronucleus; oxidative stress