title: Genotoxicity of multi-walled carbon nanotubes in both in vitro and in vivo assay systems.
abstract: The genotoxic effects of multi-walled carbon nanotubes (MWCNTs) were examined by using in vitro and in vivo assays. MWCNTs significantly induced micronuclei in A549 cells and enhanced the frequency of sister chromatid exchange (SCE) in CHO AA8 cells. When ICR mice were intratracheally instilled with a single dose (0.05 or 0.2 mg/animal) of MWCNTs, DNA damage of the lungs, analysed by comet assay, increased in a dose-dependent manner. Moreover, DNA oxidative damage, indicated by 8-oxo-7,8-dihydro-2'-deoxyguanosine and heptanone etheno-deoxyribonucleosides, occurred in the lungs of MWCNT-exposed mice. The gpt mutation frequencies significantly increased in the lungs of MWCNT-treated gpt delta transgenic mice. Transversions were predominant, and G:C to C:G was clearly increased by MWCNTs. Moreover, many regions immunohistochemically stained for inducible NO synthase and nitrotyrosine were observed in the lungs of MWCNT-exposed mice. Overall, MWCNTs were shown to be genotoxic both in in vitro and in vivo tests; the mechanisms probably involve oxidative stress and inflammatory responses.
authors.affiliation: Division of Cancer Development System, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kato
authors.forename: Yukari
authors.initials: Y
authors.lastname: Totsuka
authors.forename: Kousuke
authors.initials: K
authors.lastname: Ishino
authors.forename: Yoko
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Yukie
authors.initials: Y
authors.lastname: Tada
authors.forename: Dai
authors.initials: D
authors.lastname: Nakae
authors.forename: Sumio
authors.initials: S
authors.lastname: Goto
authors.forename: Shuichi
authors.initials: S
authors.lastname: Masuda
authors.forename: Sayaka
authors.initials: S
authors.lastname: Ogo
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kawanishi
authors.forename: Takashi
authors.initials: T
authors.lastname: Yagi
authors.forename: Tomonari
authors.initials: T
authors.lastname: Matsuda
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Watanabe
authors.forename: Keiji
authors.initials: K
authors.lastname: Wakabayashi
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D018736:DNA Adducts; D004305:Dose-Response Relationship, Drug; D015227:Lipid Peroxidation; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015162:Micronucleus Tests; D009154:Mutation / Q000187:drug effects; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*; D010084:Oxidation-Reduction; D012854:Sister Chromatid Exchange / Q000187:drug effects
chemical_list: D018736:DNA Adducts; D037742:Nanotubes, Carbon