Wang Bingyu, Li Runbing, Cai Ying, Li Boru, Qin Shuangjian, Zheng Kai, Zeng Ming, Xiao Fang, Zhang Zhaohui, Xu Xinyun
Department of Environmental Toxicology, Institute of Environment and Health, Shenzhen Center for Disease Control and Prevention, 8 Longyuan Road, Shenzhen, Guangdong 518055, China.
Department of Preventive Medicine, School of Public Health, University of South China, 28 Changsheng West Road, Hengyang, Hunan 421001, China.
Toxicol Res (Camb). 2020 Aug 18;9(4):552-560. doi: 10.1093/toxres/tfaa061. eCollection 2020 Jul.
This current study explored the effects of fine particulate matter (PM) on deoxyribonucleic acid methylation in human bronchial epithelial cells. Human bronchial epithelial cells were exposed to PM for 24 h after which, deoxyribonucleic acid samples were extracted, and the differences between methylation sites were detected using methylation chips. Subsequent gene ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed for the differential methylation sites. Functional epigenetic modules analysis of the overall differential methylation site interactions was also conducted. A total of 127 differential methylation sites in 89 genes were screened in the PM 10 μg/ml group, of which 55 sites demonstrated increased methylation, with methylation levels decreasing in a further 72 sites. Following an exposure of 50 μg/ml PM, a total of 238 differentially methylated sites were screened in 168 genes, of which methylation levels increased in 127 sites, and decreased in 111. KEGG analysis showed that the top 10 enrichment pathways predominantly involve hepatocellular carcinoma pathways and endometrial cancer pathways, whereas functional epigenetic modules analysis screened eight genes (, ) with the most interactions. Our results indicate that exposure to PM for 24 h in human bronchial epithelial cells induces marked changes in deoxyribonucleic acid methylation of multiple genes involved in apoptosis and carcinogenesis pathways, these findings can provide a new direction for further study of PM carcinogenic biomarkers.
本研究探讨了细颗粒物（PM）对人支气管上皮细胞脱氧核糖核酸甲基化的影响。将人支气管上皮细胞暴露于PM中24小时后，提取脱氧核糖核酸样本，并使用甲基化芯片检测甲基化位点之间的差异。随后对差异甲基化位点进行基因本体功能富集分析和京都基因与基因组百科全书（KEGG）分析。还对整体差异甲基化位点相互作用进行了功能表观遗传模块分析。在10μg/ml PM组中筛选出89个基因中的127个差异甲基化位点，其中55个位点甲基化增加，另外72个位点甲基化水平降低。暴露于50μg/ml PM后，在168个基因中筛选出总共238个差异甲基化位点，其中127个位点甲基化水平增加，111个位点甲基化水平降低。KEGG分析表明，前10个富集途径主要涉及肝细胞癌途径和子宫内膜癌途径，而功能表观遗传模块分析筛选出了相互作用最多的8个基因（，）。我们的结果表明，人支气管上皮细胞暴露于PM 24小时会诱导参与凋亡和致癌途径的多个基因的脱氧核糖核酸甲基化发生显著变化，这些发现可为进一步研究PM致癌生物标志物提供新方向。
