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辐射致癌中的DNA甲基化:实验证据与临床展望

DNA Methylation in Radiation-Induced Carcinogenesis: Experimental Evidence and Clinical Perspectives.

作者信息

Miousse Isabelle R, Ewing Laura E, Kutanzi Kristy R, Griffin Robert J, Koturbash Igor

机构信息

Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas.

Department of Environmental and Occupational Health, Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas.

出版信息

Crit Rev Oncog. 2018;23(1-2):1-11. doi: 10.1615/CritRevOncog.2018025687.

Abstract

Ionizing radiation is a valuable tool in many spheres of human life. At the same time, it is a genotoxic agent with a well-established carcinogenic potential. Progress achieved in the last two decades has demonstrated convincingly that ionizing radiation can also target the cellular epigenome. Epigenetics is defined as heritable changes in the expression of genes that are not due to alterations of DNA sequence but consist of specific covalent modifications of chromatin components, such as methylation of DNA, histone modifications, and control performed by non-coding RNAs. Accumulating evidence suggests that DNA methylation, a key epigenetic mechanism involved in the control of expression of genetic information, may serve as one of the driving mechanisms of radiation-induced carcinogenesis. Here, we review the literature on the effects of ionizing radiation on DNA methylation in various biological systems, discuss the role of DNA methylation in radiation carcinogenesis, and provide our opinion on the potential utilization of this knowledge in radiation oncology.

摘要

电离辐射在人类生活的许多领域都是一种有价值的工具。与此同时,它是一种具有公认致癌潜力的基因毒性剂。过去二十年取得的进展令人信服地表明,电离辐射也可以作用于细胞表观基因组。表观遗传学被定义为基因表达中的可遗传变化,这些变化不是由于DNA序列的改变,而是由染色质成分的特定共价修饰组成,如DNA甲基化、组蛋白修饰以及由非编码RNA进行的调控。越来越多的证据表明,DNA甲基化作为参与遗传信息表达控制的关键表观遗传机制之一,可能是辐射诱导致癌作用的驱动机制之一。在此,我们综述了关于电离辐射对各种生物系统中DNA甲基化影响的文献,讨论了DNA甲基化在辐射致癌中的作用,并对这一知识在放射肿瘤学中的潜在应用提出我们的看法。

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