title: Multi-walled carbon nanotubes (NM401) induce ROS-mediated HPRT mutations in Chinese hamster lung fibroblasts.
abstract: Although there is an important set of data showing potential genotoxic effects of nanomaterials (NMs) at the DNA (comet assay) and chromosome (micronucleus test) levels, few studies have been conducted to analyze their potential mutagenic effects at gene level. We have determined the ability of multi-walled carbon nanotubes (MWCNT, NM401), to induce mutations in the HPRT gene in Chinese hamster lung (V79) fibroblasts. NM401, characterized in the EU NanoGenotox project, were further studied within the EU Framework Programme Seven (FP7) project NANoREG. From the proliferation assay data we selected a dose-range of 0.12 to 12µg/cm(2) At these range we have been able to observe significant cellular uptake of MWCNT by using transmission electron microscopy (TEM), as well as a concentration-dependent induction of intracellular reactive oxygen species. In addition, a clear concentration-dependent increase in the induction of HPRT mutations was also observed. Data support a potential genotoxic/ carcinogenic risk associated with MWCNT exposure.
authors.affiliation: Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Rubio
authors.affiliation: Health Effects Laboratory-MILK, NILU-Norwegian Institute for Air Research, Kjeller, Norway.
authors.forename: Naouale
authors.initials: N
authors.lastname: El Yamani
authors.affiliation: Department of Biology, Slovak Medical University, Bratislava, Slovakia.
authors.forename: Alena
authors.initials: A
authors.lastname: Kazimirova
authors.affiliation: Health Effects Laboratory-MILK, NILU-Norwegian Institute for Air Research, Kjeller, Norway. Electronic address: maria.dusinska@nilu.no.
authors.forename: Maria
authors.initials: M
authors.lastname: Dusinska
authors.affiliation: Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra, Spain; CIBER Epidemiología y Salud Pública, Instituto de Salud Carlos III, Madrid, Spain. Electronic address: ricard.marcos@uab.es.
authors.forename: Ricard
authors.initials: R
authors.lastname: Marcos
mesh_terms: D000818:Animals; D002460:Cell Line; D003412:Cricetulus; D004249:DNA Damage; D005347:Fibroblasts / Q000187:drug effects; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics* / Q000378:metabolism; D008168:Lung / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D037742:Nanotubes, Carbon / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D009153:Mutagens; D037742:Nanotubes, Carbon; D017382:Reactive Oxygen Species; D007041:Hypoxanthine Phosphoribosyltransferase
keywords: Genotoxicity; HPRT gene; Multi-walled carbon nanotubes; ROS; V79 cells