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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/26439

Title: Differences in MWCNT- and SWCNT-induced DNA methylation alterations in association with the nuclear deposition
Authors: Oner, Deniz
Ghosh, Manosij
Bove, Hannelore
Moisse, Matthieu
Boeckx, Bram
Duca, Radu C.
Poels, Katrien
Luyts, Katrien
Putzeys, Eveline
Van Landuydt, Kirsten
Vanoirbeek, Jeroen A. J.
Ameloot, Marcel
Lambrechts, Diether
Godderis, Lode
Hoet, Peter H. M.
Issue Date: 2018
Abstract: Background: Subtle DNA methylation alterations mediated by carbon nanotubes (CNTs) exposure might contribute to pathogenesis and disease susceptibility. It is known that both multi-walled carbon nanotubes (MWCNTs) and single-walled carbon nanotubes (SWCNTs) interact with nucleus. Such, nuclear-CNT interaction may affect the DNA methylation effects. In order to understand the epigenetic toxicity, in particular DNA methylation alterations, of SWCNTs and short MWCNTs, we performed global/genome-wide, gene-specific DNA methylation and RNA-expression analyses after exposing human bronchial epithelial cells (16HBE14o-cell line). In addition, the presence of CNTs on/in the cell nucleus was evaluated in a label-free way using femtosecond pulsed laser microscopy. Results: Generally, a higher number of SWCNTs, compared to MWCNTs, was deposited at both the cellular and nuclear level after exposure. Nonetheless, both CNT types were in physical contact with the nuclei. While particle type dependency was noticed for the identified genome-wide and gene-specific alterations, no global DNA methylation alteration on 5-methylcytosine (5-mC) sites was observed for both CNTs. After exposure to MWCNTs, 2398 genes were hypomethylated (at gene promoters), and after exposure to SWCNTs, 589 CpG sites (located on 501 genes) were either hypo-(N = 493 CpG sites) or hypermethylated (N = 96 CpG sites). Cells exposed to MWCNTs exhibited a better correlation between gene promoter methylation and gene expression alterations. Differentially methylated and expressed genes induced changes (MWCNTs > SWCNTs) at different cellular pathways, such as p53 signalling, DNA damage repair and cell cycle. On the other hand, SWCNT exposure showed hypermethylation on functionally important genes, such as SKI proto-oncogene (SKI), glutathione S-transferase pi 1 (GTSP1) and shroom family member 2 (SHROOM2) and neurofibromatosis type I (NF1), which the latter is both hypermethylated and downregulated. Conclusion: After exposure to both types of CNTs, epigenetic alterations may contribute to toxic or repair response. Moreover, our results suggest that the observed differences in the epigenetic response depend on particle type and differential CNT-nucleus interactions.
Notes: Hoet, PHM (reprint author), Katholieke Univ Leuven, Dept Publ Hlth & Primary Care, Lab Toxicol Unit Environm & Hlth, B-3000 Leuven, Belgium. peter.hoet@kuleuven.be
URI: http://hdl.handle.net/1942/26439
DOI: 10.1186/s12989-018-0244-6
ISI #: 000424771100001
ISSN: 1743-8977
Category: A1
Type: Journal Contribution
Appears in Collections: Research publications

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