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Epigenetic changes in the early stage of silica-induced cell transformation.

Authors
  • Seidel, Carole1
  • Kirsch, Anaïs1
  • Fontana, Caroline1
  • Visvikis, Athanase2
  • Remy, Aurélie1
  • Gaté, Laurent1
  • Darne, Christian1
  • Guichard, Yves1
  • 1 a Département Toxicologie et Biométrologie , Institut National de Recherche et Sécurité (INRS) , Vandoeuvre-lès-Nancy Cedex , France. , (France)
  • 2 b Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA) , UMR 7365 CNRS-Université de Lorraine, Biopôle, Campus Biologie Santé , Vandoeuvre-lès-Nancy , France. , (France)
Type
Published Article
Journal
Nanotoxicology
Publisher
Informa UK (Taylor & Francis)
Publication Date
Sep 01, 2017
Volume
11
Issue
7
Pages
923–935
Identifiers
DOI: 10.1080/17435390.2017.1382599
PMID: 28958182
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The increasing use of nanomaterials in numerous domains has led to growing concern about their potential toxicological properties, and the potential risk to human health posed by silica nanoparticles remains under debate. Recent studies proposed that these particles could alter gene expression through the modulation of epigenetic marks, and the possible relationship between particle exposure and these mechanisms could represent a critical factor in carcinogenicity. In this study, using the Bhas 42 cell model, we compare the effects of exposure to two transforming particles, a pyrogenic amorphous silica nanoparticle NM-203 to those of the crystalline silica particle Min-U-Sil® 5. Short-term treatment by Min-U-Sil® 5 decreased global DNA methylation and increased the expression of the two de novo DNMTs, DNMT3a and DNMT3b. NM-203 treatment affected neither the expression of these enzymes nor DNA methylation. Moreover, modified global histone H4 acetylation status and HDAC protein levels were observed only in the Min-U-Sil® 5-treated cells. Finally, both types of particle treatment induced strong c-Myc expression in the early stage of cell transformation and this correlated with enrichment in RNA polymerase II as well as histone active marks on its promoter. Lastly, almost all parameters that were modulated in the early stage were restored in transformed cells suggesting their involvement mainly in the first steps of cell transformation.

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