title: Toxic and DNA damaging effects of a functionalized fullerene in human embryonic lung fibroblasts.
abstract: Water-soluble fullerenes have been studied as potential nanovectors and therapeutic agents, but their possible toxicity is of concern. We have studied the effects of F-828, a soluble fullerene [C60] derivative, on diploid human embryonic lung fibroblasts (HELFs) in vitro. F-828 causes complex time-dependent changes in ROS levels. Inhibition of Nox4 activity by plumbagin blocks F-828-dependent ROS elevation. F-828 induces DNA breaks, as measured by the comet assay and γH2AX expression, and the activities of the transcription factors NF-kB and p53 increase. F-828 concentrations>25μM are cytotoxic; cell death occurs by necrosis. Expression levels of TGF-β, RHOA, RHOC, ROCK1, and SMAD2 increase following exposure to F-828. Our results raise the possibility that fullerene F-828 may induce pulmonary fibrosis in vivo.
authors.affiliation: Research Centre for Medical Genetics (RCMG), Moscow, 115478, Russia; V. A. Negovsky Research Institute of General Reanimatology, Moscow, 107031, Russia.
authors.forename: E S
authors.initials: ES
authors.lastname: Ershova
authors.affiliation: Research Centre for Medical Genetics (RCMG), Moscow, 115478, Russia.
authors.forename: V A
authors.initials: VA
authors.lastname: Sergeeva
authors.affiliation: Research Centre for Medical Genetics (RCMG), Moscow, 115478, Russia.
authors.forename: A I
authors.initials: AI
authors.lastname: Chausheva
authors.affiliation: Research Centre for Medical Genetics (RCMG), Moscow, 115478, Russia.
authors.forename: D G
authors.initials: DG
authors.lastname: Zheglo
authors.affiliation: Research Centre for Medical Genetics (RCMG), Moscow, 115478, Russia.
authors.forename: V A
authors.initials: VA
authors.lastname: Nikitina
authors.affiliation: Research Centre for Medical Genetics (RCMG), Moscow, 115478, Russia.
authors.forename: T D
authors.initials: TD
authors.lastname: Smirnova
authors.affiliation: Research Centre for Medical Genetics (RCMG), Moscow, 115478, Russia.
authors.forename: L V
authors.initials: LV
authors.lastname: Kameneva
authors.affiliation: Research Centre for Medical Genetics (RCMG), Moscow, 115478, Russia. Electronic address: med-gen@mail.ru.
authors.forename: L N
authors.initials: LN
authors.lastname: Porokhovnik
authors.affiliation: Research Centre for Medical Genetics (RCMG), Moscow, 115478, Russia; N.I. Pirogov Russian National Research Medical University, Moscow, 117997, Russia.
authors.forename: S I
authors.initials: SI
authors.lastname: Kutsev
authors.affiliation: Institute for Problems of Chemical Physics of Russian Academy of Sciences, Moscow Region, 142432, Russia.
authors.forename: P A
authors.initials: PA
authors.lastname: Troshin
authors.affiliation: Institute for Problems of Chemical Physics of Russian Academy of Sciences, Moscow Region, 142432, Russia.
authors.forename: I I
authors.initials: II
authors.lastname: Voronov
authors.affiliation: Institute for Problems of Chemical Physics of Russian Academy of Sciences, Moscow Region, 142432, Russia.
authors.forename: E A
authors.initials: EA
authors.lastname: Khakina
authors.affiliation: Research Centre for Medical Genetics (RCMG), Moscow, 115478, Russia; V. A. Negovsky Research Institute of General Reanimatology, Moscow, 107031, Russia.
authors.forename: N N
authors.initials: NN
authors.lastname: Veiko
authors.affiliation: Research Centre for Medical Genetics (RCMG), Moscow, 115478, Russia.
authors.forename: S V
authors.initials: SV
authors.lastname: Kostyuk
mesh_terms: D002460:Cell Line; D020552:Comet Assay; D004247:DNA / Q000187:drug effects / Q000235:genetics*; D053960:DNA Breaks / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism*; D037741:Fullerenes / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D008168:Lung / Q000166:cytology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D037741:Fullerenes; D017382:Reactive Oxygen Species; D004247:DNA
keywords: Comet assay; DNA damage; Fibroblasts; Free radicals; Fullerene