title: Single-walled carbon nanotubes: differential genotoxic potential associated with physico-chemical properties.
abstract: Single-walled carbon nanotubes (SWCNTs) have recently attracted great attention because of their fibrous structure and high aspect ratio. Here the genotoxic potential of 400-800 nm, 1-3 μm and 5-30 μm SWCNT with respect to their geometry and surface characteristics was studied. Following thorough physico-chemical characterisation, human bronchial epithelial (BEAS-2B) and lymphoblastoid (MCL-5) cells were treated with SWCNT for 24 or 48 h. This showed significant increases in micronucleus frequency in a time- and dose-dependent manner in both cell types in the absence of cytotoxicity. Over the same dose range, only 1-3 μm SWCNT gave rise to significant increases in hprt point mutations at doses ≥25 μg/ml. Cellular 2,7-dichlorodihydrofluoresceindiacetate (DCFH-DA) fluorescence assay and RT-PCR for oxidative pathway gene profiling revealed a possible oxidative mechanism for the genotoxicity observed in the 1-3 μm SWCNT. Consequently, this study has demonstrated that SWCNT genotoxicity is dependent on its secondary structure under experimental conditions and oxidative stress alone cannot account for the observed damage.
authors.affiliation: Institute of Life Science, School of Medicine, Swansea University, Singleton Park, Swansea, UK. b.manshian@swansea.ac.uk
authors.forename: Bella B
authors.initials: BB
authors.lastname: Manshian
authors.forename: Gareth Js
authors.initials: GJ
authors.lastname: Jenkins
authors.forename: Paul M
authors.initials: PM
authors.lastname: Williams
authors.forename: Chris
authors.initials: C
authors.lastname: Wright
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Barron
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Brown
authors.forename: Nicole
authors.initials: N
authors.lastname: Hondow
authors.forename: Peter R
authors.initials: PR
authors.lastname: Dunstan
authors.forename: Rob
authors.initials: R
authors.lastname: Rickman
authors.forename: Ken
authors.initials: K
authors.lastname: Brady
authors.forename: Shareen H
authors.initials: SH
authors.lastname: Doak
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D015394:Molecular Structure; D016296:Mutagenesis; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity*; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013329:Structure-Activity Relationship; D013499:Surface Properties; D013997:Time Factors
chemical_list: D009153:Mutagens; D037742:Nanotubes, Carbon; D007041:Hypoxanthine Phosphoribosyltransferase