Schofield Paul N, Kondratowicz Monika
a Department of Physiology, Development, and Neuroscience , University of Cambridge , Cambridge , UK.
Int J Radiat Biol. 2018 Aug;94(8):769-781. doi: 10.1080/09553002.2017.1388548. Epub 2017 Dec 1.
In the late 1990s, it had become clear that the long-standing paradigm for the action of radiation on living cells and organisms did not have sufficient power to explain the observed effects of low dose ionizing radiation. The purpose of this commentary is to examine the experiments that lead up to the modification of the classic paradigm consequent on these observations, their historical precedents, and the development of our understanding of the role of epigenetics in low dose radiation effects.
We discuss how parallel advances in epigenetics from developmental biology and cancer studies, and the discovery of epigenetic modifications of chromatin, such as DNA methylation, impacted on the development of an epigenetic paradigm for low dose effects. We also assess the impact of technology development in supporting the paradigm shift. We then examine recent accumulated data on epigenetic modification in response to irradiation since that shift took place, and identify areas where bringing together data from developmental biology and cancer might answer some of the paradoxes and contradictions in this data. We predict that further paradigm shifts are imminent.
在20世纪90年代后期,很明显长期以来关于辐射对活细胞和生物体作用的范式没有足够的能力来解释低剂量电离辐射所观察到的效应。本评论的目的是审视那些导致基于这些观察结果对经典范式进行修正的实验、它们的历史先例,以及我们对表观遗传学在低剂量辐射效应中作用的理解的发展。
我们讨论了发育生物学和癌症研究中表观遗传学的平行进展,以及染色质表观遗传修饰(如DNA甲基化)的发现如何影响低剂量效应表观遗传范式的发展。我们还评估了技术发展在支持这一范式转变方面的影响。然后,我们审视了自该转变发生以来关于辐射后表观遗传修饰的最新积累数据,并确定将发育生物学和癌症的数据结合起来可能解决该数据中一些矛盾和冲突的领域。我们预测进一步的范式转变即将到来。