Miousse Isabelle R, Tobacyk Julia, Melnyk Stepan, James S Jill, Cheema Amrita K, Boerma Marjan, Hauer-Jensen Martin, Koturbash Igor
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Biomol Concepts. 2017 May 24;8(2):83-92. doi: 10.1515/bmc-2017-0003.
Ionizing radiation (IR) is a ubiquitous component of our environment and an important tool in research and medical treatment. At the same time, IR is a potent genotoxic and epigenotoxic stressor, exposure to which may lead to negative health outcomes. While the genotoxocity is well described and characterized, the epigenetic effects of exposure to IR and their mechanisms remain under-investigated. In this conceptual review, we propose the IR-induced changes to one-carbon metabolism as prerequisites to alterations in the cellular epigenome. We also provide evidence from both experimental and clinical studies describing the interactions between IR and one-carbon metabolism. We further discuss the potential for the manipulation of the one-carbon metabolism in clinical applications for the purpose of normal tissue protection and for increasing the radiosensitivity of cancerous cells.
电离辐射(IR)是我们环境中普遍存在的组成部分,也是研究和医学治疗中的重要工具。同时,IR是一种强大的基因毒性和表观遗传毒性应激源,接触它可能会导致负面的健康后果。虽然基因毒性已得到充分描述和表征,但接触IR的表观遗传效应及其机制仍未得到充分研究。在这篇概念性综述中,我们提出IR诱导的一碳代谢变化是细胞表观基因组改变的先决条件。我们还提供了来自实验和临床研究的证据,描述了IR与一碳代谢之间的相互作用。我们进一步讨论了在临床应用中操纵一碳代谢以保护正常组织和提高癌细胞放射敏感性的潜力。