Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2147799 | Mutation Research/Genetic Toxicology and Environmental Mutagenesis | 2016 | 12 Pages |
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 >25 μM 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.
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Authors
E.S. Ershova, V.A. Sergeeva, A.I. Chausheva, D.G. Zheglo, V.A. Nikitina, T.D. Smirnova, L.V. Kameneva, L.N. Porokhovnik, S.I. Kutsev, P.A. Troshin, I.I. Voronov, E.A. Khakina, N.N. Veiko, S.V. Kostyuk,