title: Epigenetic effects of carbon nanotubes in human monocytic cells.
abstract: Carbon nanotubes (CNTs) are fibrous carbon-based nanomaterials with a potential to cause carcinogenesis in humans. Alterations in DNA methylation on cytosine-phosphate-guanidine (CpG) sites are potential markers of exposure-induced carcinogenesis. This study examined cytotoxicity, genotoxicity and DNA methylation alterations on human monocytic cells (THP-1) after incubation with single-walled CNTs (SWCNTs) and multi-walled CNTs (MWCNTs). Higher cytotoxicity and genotoxicity were observed after incubation with SWCNTs than incubation with MWCNTs. At the selected concentrations (25 and 100 µg/ml), DNA methylation alterations were studied. Liquid chromatography-mass spectrometry (LC-MS/MS) was used to assess global DNA methylation, and Illumina 450K microarrays were used to assess methylation of single CpG sites. Next, we assessed gene promoter-specific methylation levels. We observed no global methylation or hydroxymethylation alterations, but on gene-specific level, distinct clustering of CNT-treated samples were noted. Collectively, CNTs induced gene promoter-specific altered methylation and those 1127 different genes were identified to be hypomethylated. Differentially methylated genes were involved in several signalling cascade pathways, vascular endothelial growth factor and platelet activation pathways. Moreover, possible contribution of the epigenetic alterations to monocyte differentiation and mixed M1/M2 macrophage polarisation were discussed.
authors.affiliation: Laboratory of Toxicology, Unit of Environment and Health, Department of Public Health and Primary Care, O & N I Herestraat 49 bus 706, 3000 Leuven, Belgium.
authors.forename: Deniz
authors.initials: D
authors.lastname: Öner
authors.affiliation: Laboratory of Translational Genetics, Department of Oncology, O & N IV Herestraat 49 bus 912, 3000 Leuven, Belgium.|VIB Vesalius Research Center, O & N I Herestraat 49 bus 912, 3000 Leuven, Belgium and.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Moisse
authors.affiliation: Laboratory of Toxicology, Unit of Environment and Health, Department of Public Health and Primary Care, O & N I Herestraat 49 bus 706, 3000 Leuven, Belgium.
authors.forename: Manosij
authors.initials: M
authors.lastname: Ghosh
authors.affiliation: Laboratory for Occupational and Environmental Hygiene, Unit of Environment and Health, Department of Public Health and Primary Care, Kapucijnenvoer 35 blok d bus 7001, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Radu C
authors.initials: RC
authors.lastname: Duca
authors.affiliation: Laboratory for Occupational and Environmental Hygiene, Unit of Environment and Health, Department of Public Health and Primary Care, Kapucijnenvoer 35 blok d bus 7001, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: Poels
authors.affiliation: Laboratory of Toxicology, Unit of Environment and Health, Department of Public Health and Primary Care, O & N I Herestraat 49 bus 706, 3000 Leuven, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: Luyts
authors.affiliation: Laboratory of Toxicology, Unit of Environment and Health, Department of Public Health and Primary Care, O & N I Herestraat 49 bus 706, 3000 Leuven, Belgium.|Unit of Biomaterials (BIOMAT), Department of Oral Health Sciences, KU Leuven, Campus Sint-Raphael, Kapucijnenvoer 7, Block A-box 7001, 3000 Leuven, Belgium and.
authors.forename: Eveline
authors.initials: E
authors.lastname: Putzeys
authors.affiliation: Unit of Biomaterials (BIOMAT), Department of Oral Health Sciences, KU Leuven, Campus Sint-Raphael, Kapucijnenvoer 7, Block A-box 7001, 3000 Leuven, Belgium and.
authors.forename: Stevan M
authors.initials: SM
authors.lastname: Cokic
authors.affiliation: Unit of Biomaterials (BIOMAT), Department of Oral Health Sciences, KU Leuven, Campus Sint-Raphael, Kapucijnenvoer 7, Block A-box 7001, 3000 Leuven, Belgium and.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Van Landuyt
authors.affiliation: Laboratory of Toxicology, Unit of Environment and Health, Department of Public Health and Primary Care, O & N I Herestraat 49 bus 706, 3000 Leuven, Belgium.|Laboratory for Occupational and Environmental Hygiene, Unit of Environment and Health, Department of Public Health and Primary Care, Kapucijnenvoer 35 blok d bus 7001, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Vanoirbeek
authors.affiliation: Laboratory of Translational Genetics, Department of Oncology, O & N IV Herestraat 49 bus 912, 3000 Leuven, Belgium.|VIB Vesalius Research Center, O & N I Herestraat 49 bus 912, 3000 Leuven, Belgium and.
authors.forename: Diether
authors.initials: D
authors.lastname: Lambrechts
authors.affiliation: Laboratory of Toxicology, Unit of Environment and Health, Department of Public Health and Primary Care, O & N I Herestraat 49 bus 706, 3000 Leuven, Belgium.|External Service for Prevention and Protection at Work, IDEWE, Interleuvenlaan 58, 3001 Leuven, Belgium.
authors.forename: Lode
authors.initials: L
authors.lastname: Godderis
authors.affiliation: Laboratory of Toxicology, Unit of Environment and Health, Department of Public Health and Primary Care, O & N I Herestraat 49 bus 706, 3000 Leuven, Belgium, peter.hoet@med.kuleuven.be.
authors.forename: Peter H M
authors.initials: PH
authors.lastname: Hoet
mesh_terms: D002853:Chromatography, Liquid; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D019175:DNA Methylation / Q000187:drug effects*; D044127:Epigenesis, Genetic / Q000187:drug effects*; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000187:drug effects / Q000235:genetics; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009152:Mutagenicity Tests; D037742:Nanotubes, Carbon / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D053719:Tandem Mass Spectrometry
chemical_list: D037742:Nanotubes, Carbon; D004247:DNA