Changes in DNA methylation induced by multi-walled carbon nanotube exposure in the workplace

<p>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 (<i>L1RE1)</i> elements, and promoter regions of functionally important genes associated with epigenetic regulation [DNA methyltransferase-1 (<i>DNMT1)</i> and histone deacetylase 4 (<i>HDAC4</i>)], DNA damage/repair and cell cycle pathways [nuclear protein, coactivator of histone transcription/ATM serine/threonine kinase <i>(NPAT/ATM)</i>], and a potential transforming growth factor beta (TGF-β) repressor [SKI proto-oncogene <i>(SKI</i>)] 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 <i>LINE1</i> (L1RE1) elements. Further analysis of gene-specific DNA methylation showed a significant change in methylation for <i>DNMT1, ATM, SKI</i>, and <i>HDAC4</i> 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.</p>