KU Leuven, Department of Public Health and Primary Care, Unit of Environment and Health, Laboratory of Toxicology, 3000 Leuven, Belgium.
KU Leuven, Department of Human Genetics, Laboratory for Translational Genetics, Leuven, Belgium; VIB, VIB Center for Cancer Biology, Laboratory for Translational Genetics, Leuven, Belgium.
Environ Int. 2018 Jun;115:301-311. doi: 10.1016/j.envint.2018.03.031. Epub 2018 Apr 5.
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 >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.
吸入暴露于石棉与人类肺部和胸膜疾病有关，仍然是全球主要的公共卫生问题。人类支气管上皮细胞（16HBE）暴露于 UICC 青石棉、温石棉和透闪石。在不同剂量（2.5-100μg/ml）下研究细胞毒性、遗传毒性和胞嘧啶残基的全基因组 DNA 甲基化（使用 LC-MS/MS）。使用微阵列研究整个基因组的基因特异性 DNA 甲基化改变，该微阵列可检测 >450 万个 CpG 位点。随后，对具有差异甲基化基因启动子的基因进行基因功能分析（KEGG 途径、基因本体论和功能分类）。在非细胞毒性剂量下，暴露于青石棉和温石棉（石棉类纤维） 24 小时后，全基因组 DNA 甲基化发生改变（>2.5μg/ml）。青石棉和温石棉（石棉类纤维）暴露会导致单个 CpG 位点和基因启动子水平的低甲基化和高甲基化，而透闪石（蛇纹石类纤维）暴露会导致基因启动子水平的低甲基化。基因功能分类分析表明，所有类型的石棉纤维都会导致 GO 簇的改变，即 Rho 蛋白信号转导的调节、细胞核（如同源盒基因）、ATP 结合功能和细胞外区域（如 WNT 基因家族）。这些差异甲基化基因可能导致支气管细胞与石棉相关的疾病。
