Global and gene-specific DNA methylation effects of different asbestos fibres on human bronchial epithelial cells
Autor: | Manosij Ghosh, Robin Coorens, Radu Corneliu Duca, Lode Godderis, Deniz Öner, Diether Lambrechts, Peter Hoet, Jeroen Vanoirbeek, Matthieu Moisse |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Microarray PATHOGENESIS GENOTOXICITY Environmental Sciences & Ecology Biology RHO-GTPASES medicine.disease_cause Asbestos Cell Line 03 medical and health sciences POOR-PROGNOSIS Chrysotile medicine PROMOTER METHYLATION Humans Gene lcsh:Environmental sciences General Environmental Science lcsh:GE1-350 Inhalation exposure Inhalation Exposure Science & Technology CARCINOGENESIS Epithelial Cells Promoter DNA Methylation CANCER Molecular biology MALIGNANT PLEURAL MESOTHELIOMA 030104 developmental biology CpG site DNA methylation Life Sciences & Biomedicine Environmental Sciences LUNG CHRYSOTILE |
Zdroj: | Environment International, Vol 115, Iss, Pp 301-311 (2018) |
ISSN: | 0160-4120 |
Popis: | Inhalation exposure to asbestos is associated with lung and pleural diseases in humans and remains a major public health issue worldwide. Human bronchial epithelial cells (16HBE) were exposed to UICC amosite, crocidolite and chrysotile. Cytotoxicity, genotoxicity, global DNA methylation on cytosine residues (using LC-MS/MS) were investigated at different doses (2.5-100 µg/ml). Gene-specific DNA methylation alterations at the whole genome were investigated using a microarray that interrogates more than 450 thousand CpG sites. Subsequently, gene functional analyses (KEGG pathway, Gene Ontology and functional classification) were performed on genes with differentially methylated gene promoters. At non-cytotoxic doses, global DNA methylation was altered after 24 h exposure to amosite and crocidolite (> 2.5 µg/ml). Exposure to amosite and crocidolite (amphibole type asbestos) induced both hypomethylation and hypermethylation at single CpG site and gene promoter levels whereas exposure to chrysotile (serpentine type asbestos) induced hypomethylation at the gene promoter level. Gene functional classification analyses revealed that all types of asbestos fibres induce alterations on GO-clusters i.e on regulation of Rho-protein signal transduction, nucleus, (e.g. homeobox genes), ATP-binding function and extracellular region (e.g. WNT-group of genes). These differentially methylated genes might contribute to asbestos-related diseases in bronchial cells. ispartof: Environment International vol:115 pages:301-311 ispartof: location:Netherlands status: published |
Databáze: | OpenAIRE |
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