Changes in DNA methylation induced by multi-walled carbon nanotube exposure in the workplace. Issue 9 (26th November 2017)

• Record Type: Journal Article
• Authors: Ghosh, Manosij; Öner, Deniz; Poels, Katrien; Tabish, Ali M.; Vlaanderen, Jelle; Pronk, Anjoeka; Kuijpers, Eelco; Lan, Qing; Vermeulen, Roel; Bekaert, Bram; Hoet, Peter HM; Godderis, Lode
• Is Part Of: Nanotoxicology. Volume 11:Issue 9/10(2017)
• Page Start: 1195
• Page End: 1210
• Publication Date: 2017-11-26
• Subjects: Epigenetics -- DNA methylation -- carbon nanotubes -- occupational exposure; Toxicology -- Periodicals; 615.9
• DOI: 10.1080/17435390.2017.1406169
• Languages: English
• ISSNs: 1743-5390

Abstract

Abstract: This study was designed to assess the epigenetic alterations in blood cells, induced by occupational exposure to multi-wall carbon nanotubes (MWCNT). The study population comprised of MWCNT-exposed workers (n=24) and unexposed controls (n=43) from the same workplace. We measured global DNA methylation/hydroxymethylation levels on the 5th cytosine residues using a validated liquid chromatography tandem-mass spectrometry (LC-MS/MS) method. Sequence-specific methylation of LINE1 retrotransposable element 1 ( L1RE1) elements, and promoter regions of functionally important genes associated with epigenetic regulation [DNA methyltransferase-1 ( DNMT1) and histone deacetylase 4 ( HDAC4 )], DNA damage/repair and cell cycle pathways [nuclear protein, coactivator of histone transcription/ATM serine/threonine kinase (NPAT/ATM) ], and a potential transforming growth factor beta (TGF-β) repressor [SKI proto-oncogene (SKI )] were studied using bisulfite pyrosequencing. Analysis of global DNA methylation levels and hydroxymethylation did not reveal significant difference between the MWCNT-exposed and control groups. No significant changes in Cytosine-phosphate-Guanine (CpG) site methylation were observed for the LINE1 (L1RE1) elements. Further analysis of gene-specific DNA methylation showed a significant change in methylation for DNMT1, ATM, SKI, and HDAC4 promoter CpGs in MWCNT-exposed workers. Since DNA methylation plays an important role in silencing/regulation of the genes, and many of these genes have been associated with occupational and smoking-induced diseases and cancer (risk), aberrant methylation of these genes might have a potential effect in MWCNT-exposed workers.