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评估极低频磁场暴露与氧化应激对人神经细胞中LINE-1启动子甲基化的联合作用。

Assessing the combined effect of extremely low-frequency magnetic field exposure and oxidative stress on LINE-1 promoter methylation in human neural cells.

作者信息

Giorgi Gianfranco, Pirazzini Chiara, Bacalini Maria Giulia, Giuliani Cristina, Garagnani Paolo, Capri Miriam, Bersani Ferdinando, Del Re Brunella

机构信息

Department of Pharmacy and Biotechnology (FaBiT), University of Bologna, via Selmi 3, 40126, Bologna, Italy.

Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, via S. Giacomo 12, 40126, Bologna, Italy.

出版信息

Radiat Environ Biophys. 2017 May;56(2):193-200. doi: 10.1007/s00411-017-0683-8. Epub 2017 Mar 3.

DOI:10.1007/s00411-017-0683-8
PMID:28258386
Abstract

Extremely low frequency magnetic fields (ELF-MF) have been classified as "possibly carcinogenic", but their genotoxic effects are still unclear. Recent findings indicate that epigenetic mechanisms contribute to the genome dysfunction and it is well known that they are affected by environmental factors. To our knowledge, to date the question of whether exposure to ELF-MF can influence epigenetic modifications has been poorly addressed. In this paper, we investigated whether exposure to ELF-MF alone and in combination with oxidative stress (OS) can affect DNA methylation, which is one of the most often studied epigenetic modification. To this end, we analyzed the DNA methylation levels of the 5'untranslated region (5'UTR) of long interspersed nuclear element-1s (LINE-1 or L1), which are commonly used to evaluate the global genome methylation level. Human neural cells (BE(2)C) were exposed for 24 and 48 h to extremely low frequency pulsed magnetic field (PMF; 50 Hz, 1 mT) in combination with OS. The methylation levels of CpGs located in L1 5'UTR region were measured by MassARRAY EpiTYPER. The results indicate that exposures to the single agents PMF and OS induced weak decreases and increases of DNA methylation levels at different CpGs. However, the combined exposure to PMF and OS lead to significant decrease of DNA methylation levels at different CpG sites. Most of the changes were transient, suggesting that cells can restore homeostatic DNA methylation patterns. The results are discussed and future research directions outlined.

摘要

极低频磁场(ELF-MF)已被归类为“可能致癌”,但其遗传毒性作用仍不清楚。最近的研究结果表明,表观遗传机制会导致基因组功能障碍,并且众所周知,它们会受到环境因素的影响。据我们所知,迄今为止,关于暴露于ELF-MF是否会影响表观遗传修饰的问题尚未得到充分探讨。在本文中,我们研究了单独暴露于ELF-MF以及与氧化应激(OS)联合暴露是否会影响DNA甲基化,DNA甲基化是最常研究的表观遗传修饰之一。为此,我们分析了长散在核元件-1(LINE-1或L1)的5'非翻译区(5'UTR)的DNA甲基化水平,该区域通常用于评估全基因组甲基化水平。将人类神经细胞(BE(2)C)暴露于极低频脉冲磁场(PMF;50Hz,1mT)24小时和48小时,并联合氧化应激。通过MassARRAY EpiTYPER测量位于L1 5'UTR区域的CpG的甲基化水平。结果表明,单独暴露于PMF和OS会导致不同CpG处的DNA甲基化水平出现微弱的降低和升高。然而,PMF和OS的联合暴露导致不同CpG位点的DNA甲基化水平显著降低。大多数变化是短暂的,这表明细胞可以恢复稳态的DNA甲基化模式。我们对结果进行了讨论,并概述了未来的研究方向。

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