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单壁和多壁碳纳米管在16HBE细胞中诱导序列特异性表观遗传改变。

Single-walled and multi-walled carbon nanotubes induce sequence-specific epigenetic alterations in 16 HBE cells.

作者信息

Ghosh Manosij, Öner Deniz, Duca Radu C, Bekaert Bram, Vanoirbeek Jeroen A J, Godderis Lode, Hoet Peter H M

机构信息

KU Leuven, Department of Public Health and Primary Care, Centre Environment and Health, B-3000 Leuven, Belgium.

Forensic Biomedical Sciences, Department of Imaging and Pathology, KU Leuven, University of Leuven, Leuven, Belgium.

出版信息

Oncotarget. 2018 Apr 17;9(29):20351-20365. doi: 10.18632/oncotarget.24866.

Abstract

Recent studies have identified carbon nanotube (CNT)-induced epigenetic changes as one of the key players in patho-physiological response. In the present study, we investigated whether CNT exposure is associated with epigenetic changes in human bronchial epithelial cells (16 HBE), . We focused on global DNA methylation, methylation of elements and promoter sequence of twelve functionally important genes (, and ). Additionally, we studied the influence of CNT exposure on miRNA expression. Using a LC-MS/MS method and pyrosequencing for , we observed no significant changes in global DNA methylation (%) between the concentrations of multi-walled and single-walled CNT (MWCNT and SWCNT, respectively). Significant changes in sequence-specific methylation was observed in at least one CpG site for (SWCNT), (MWCNT), (MWCNT and SWCNT), (MWCNT), (MWCNT and SWCNT) and (SWCNT). While changes in DNA methylation of the genes were relatively small, these changes were associated with changes in RNA expression, especially for MWCNT. However, the study did not reveal any significant alteration in the miRNA expression, associated with MWCNT and SWCNT exposure. Based on our results, mainly MWCNT influence DNA methylation and expression of the studied genes and could have significant impact on several critical cellular processes.

摘要

最近的研究已确定碳纳米管(CNT)诱导的表观遗传变化是病理生理反应的关键因素之一。在本研究中,我们调查了碳纳米管暴露是否与人类支气管上皮细胞(16HBE)的表观遗传变化有关。我们重点关注整体DNA甲基化、12个功能重要基因(、和)的元件甲基化及启动子序列。此外,我们研究了碳纳米管暴露对miRNA表达的影响。使用LC-MS/MS方法和焦磷酸测序法进行研究,我们观察到多壁碳纳米管和单壁碳纳米管(分别为MWCNT和SWCNT)不同浓度之间的整体DNA甲基化(%)没有显著变化。在至少一个CpG位点观察到(SWCNT)、(MWCNT)、(MWCNT和SWCNT)、(MWCNT)、(MWCNT和SWCNT)和(SWCNT)的序列特异性甲基化有显著变化。虽然这些基因的DNA甲基化变化相对较小,但这些变化与RNA表达的变化有关,尤其是对于MWCNT。然而,该研究未发现与MWCNT和SWCNT暴露相关的miRNA表达有任何显著改变。根据我们的结果,主要是MWCNT影响所研究基因的DNA甲基化和表达,并可能对几个关键细胞过程产生重大影响。

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