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低剂量辐射诱导的反应:聚焦于表观遗传调控。

Low-dose radiation-induced responses: focusing on epigenetic regulation.

作者信息

Ma Shumei, Liu Xin, Jiao Benzheng, Yang Yu, Liu Xiaodong

机构信息

Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, Changchun, China.

出版信息

Int J Radiat Biol. 2010 Jul;86(7):517-28. doi: 10.3109/09553001003734592.

Abstract

PURPOSE

With the widespread use of ionising radiation, the risks of low-dose radiation have been increasingly highlighted for special attention. This review introduces the potential role of epigenetic elements in the regulation of the effects of low-dose radiation.

MATERIALS AND METHODS

The related literature has been analysed according to the topics of DNA methylation, histone modifications, chromatin remodelling and non-coding RNA modulation in low-dose radiation responses.

RESULTS

DNA methylation and radiation can reciprocally regulate effects, especially in the low-dose radiation area. The relationship between histone methylation and radiation mainly exists in the high-dose radiation area; histone deacetylase inhibitors show a promising application to enhance radiation sensitivity, both in the low-dose and high-dose areas; phosphorylated histone 2 AX (H2AX) shows a low sensitivity with 1-15 Gy irradiation as compared with lower dose radiation; and histone ubiquitination plays an important role in DNA damage repair mechanisms. Moreover, chromatin remodelling has an integral role in the repair of DNA double-strand breaks and the response of chromatin to ionising radiation. Finally, the effect of radiation on microRNA expression seems to vary according to cell type, radiation dose, and post-irradiation time point.

CONCLUSION

Small advances have been made in the understanding of epigenetic regulation of low-dose radiation responses. Many questions and blind spots deserve to be investigated. Many new epigenetic elements will be identified in low-dose radiation responses, which may give new insights into the mechanisms of radiation response and their exploitation in radiotherapy.

摘要

目的

随着电离辐射的广泛应用,低剂量辐射的风险日益受到特别关注。本综述介绍了表观遗传因素在低剂量辐射效应调控中的潜在作用。

材料与方法

根据低剂量辐射反应中DNA甲基化、组蛋白修饰、染色质重塑和非编码RNA调控等主题对相关文献进行了分析。

结果

DNA甲基化与辐射可相互调节效应,尤其是在低剂量辐射领域。组蛋白甲基化与辐射的关系主要存在于高剂量辐射领域;组蛋白去乙酰化酶抑制剂在增强低剂量和高剂量辐射敏感性方面显示出有前景的应用;与低剂量辐射相比,磷酸化组蛋白2AX(H2AX)在1-15 Gy照射下敏感性较低;组蛋白泛素化在DNA损伤修复机制中起重要作用。此外,染色质重塑在DNA双链断裂修复和染色质对电离辐射的反应中具有不可或缺的作用。最后,辐射对微小RNA表达的影响似乎因细胞类型、辐射剂量和照射后时间点而异。

结论

在低剂量辐射反应的表观遗传调控理解方面已取得一些进展。许多问题和盲点值得研究。在低剂量辐射反应中将鉴定出许多新的表观遗传因素,这可能为辐射反应机制及其在放射治疗中的应用提供新的见解。

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