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暴露于多壁碳纳米管的人肺上皮细胞中的DNA甲基化变化。

DNA methylation changes in human lung epithelia cells exposed to multi-walled carbon nanotubes.

作者信息

Sierra Marta I, Rubio Laura, Bayón Gustavo F, Cobo Isabel, Menendez Pablo, Morales Paula, Mangas Cristina, Urdinguio Rocio G, Lopez Virginia, Valdes Adolfo, Vales Gerard, Marcos Ricard, Torrecillas Ramon, Fernández Agustin F, Fraga Mario F

机构信息

a Cancer Epigenetics Lab , Institute of Oncology of Asturias (IUOPA), HUCA, Universidad de Oviedo, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA) , Oviedo , Spain.

b Grup de Mutagenesi, Departament de Genetica i de Microbiologia , Facultat de Biociencies, Universitat Autonoma de Barcelona , Barcelona , Spain ; CIBER Epidemiologia y Salud Publica, ISCIII , Madrid , Spain.

出版信息

Nanotoxicology. 2017 Sep;11(7):857-870. doi: 10.1080/17435390.2017.1371350. Epub 2017 Sep 13.

Abstract

Humans are increasingly exposed to nanoparticles and, although many of their physiological effects have been described, the molecular mechanisms underlying them are still largely unknown. The present study aimed to determine the possible role of certain epigenetic mechanisms in the cellular response of human lung epithelial cells that are triggered by long-term exposure to titanium dioxide nanoparticles (TiONPs) and multi-walled carbon nanotubes (MWCNTs). The results showed that exposure to TiONPs had only minor effects on genome-wide DNA methylation. However, we identified 755 CpG sites showing consistent DNA hypomethylation in cells exposed to MWCNTs. These sites were mainly located at low density CpG regions and enhancers, and very frequently on the X chromosome. Our results thus suggest that long-term MWCNT exposure may have important effects on the epigenome.

摘要

人类越来越多地接触到纳米颗粒,尽管已经描述了它们的许多生理效应,但其潜在的分子机制仍 largely 未知。本研究旨在确定某些表观遗传机制在长期暴露于二氧化钛纳米颗粒(TiONPs)和多壁碳纳米管(MWCNTs)所引发的人肺上皮细胞的细胞反应中的可能作用。结果表明,暴露于 TiONPs 对全基因组 DNA 甲基化仅有轻微影响。然而,我们在暴露于 MWCNTs 的细胞中鉴定出 755 个显示一致 DNA 低甲基化的 CpG 位点。这些位点主要位于低密度 CpG 区域和增强子上,并且非常频繁地位于 X 染色体上。因此,我们的结果表明长期暴露于 MWCNTs 可能对表观基因组有重要影响。

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