Literature DB >> 27402482

Toxic and DNA damaging effects of a functionalized fullerene in human embryonic lung fibroblasts.

E S Ershova1, V A Sergeeva2, A I Chausheva2, D G Zheglo2, V A Nikitina2, T D Smirnova2, L V Kameneva2, L N Porokhovnik3, S I Kutsev4, P A Troshin5, I I Voronov5, E A Khakina5, N N Veiko1, S V Kostyuk2.   

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.
Copyright © 2016 Elsevier B.V. All rights reserved.

Entities:  

Keywords:  Comet assay; DNA damage; Fibroblasts; Free radicals; Fullerene

Mesh:

Substances:

Year:  2016        PMID: 27402482     DOI: 10.1016/j.mrgentox.2016.05.004

Source DB:  PubMed          Journal:  Mutat Res Genet Toxicol Environ Mutagen        ISSN: 1383-5718            Impact factor:   2.873


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