Changes in DNA methylation induced by multi-walled carbon nanotube exposure in the workplace
article
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-ß) 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. © 2017 Informa UK Limited, trading as Taylor & Francis Group. Chemicals / CAS bisulfite, 15181-46-1, 7631-90-5, 7773-03-7; cytosine, 71-30-7; DNA, 9007-49-2; DNA (cytosine 5) methyltransferase; DNA (cytosine 5) methyltransferase 1; Air Pollutants, Occupational; DNA; DNA (Cytosine-5-)-Methyltransferase 1; DNMT1 protein, human; Nanotubes, Carbon; Transforming Growth Factor beta.
Topics
carbon nanotubesDNA methylationEpigeneticsoccupational exposureATM proteinbisulfitecytosineDNA methyltransferase 1histone deacetylase 4multi walled nanotubecarbon nanotubeDNADNA (cytosine 5) methyltransferase 1DNMT1 protein, humantransforming growth factor betacell cyclecontrolled studyCpG islandcross-sectional studyDNA damageDNA methylationDNA repairDNA structuregenegenetic associationgenetic regulationhydroxymethylationLINE1 retrotransposable element 1liquid chromatography-mass spectrometrymethylationnuclear protein coactivator of histone transcription geneoccupational exposurepriority journalpromoter regionpyrosequencingsequence analysisair pollutantanalysisDNA methylationdrug effectsgenetic epigenesisgeneticslong interspersed repeatoccupational exposurestandardstoxicityAdultAir Pollutants, OccupationalCross-Sectional StudiesDNADNA (Cytosine-5-)-Methyltransferase 1DNA MethylationEpigenesis, GeneticFemaleHumansLong Interspersed Nucleotide ElementsMaleNanotubes, CarbonOccupational ExposureTransforming Growth Factor betaWorkplace
TNO Identifier
954819
ISSN
17435390
Source
Nanotoxicology, 11(9-10), pp. 1195-1210.
Pages
1195-1210
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