Rübe Claudia E, Al-Razaq Mutaz A Abd, Meier Carola, Hecht Markus, Rübe Christian
Department of Radiation Oncology, Saarland University Medical Center, 66421 Homburg, Germany.
Department of Anatomy and Cell Biology, Medical Faculty, Saarland University, 66421 Homburg, Germany.
Epigenomes. 2025 Aug 8;9(3):29. doi: 10.3390/epigenomes9030029.
The impact of ionizing radiation (IR) with induction of various DNA damage is based not only on genetic but also on epigenetic effects. Epigenetic modifications determine the chromatin structure and DNA accessibility, thereby regulating cellular functions through the expression of individual genes or entire groups of genes. However, the influence of DNA repair processes on the restoration of local chromatin structures and global nuclear architectures is still insufficiently understood. In multicellular organisms, epigenetic mechanisms control diverse cellular functions of specific cell types through precise temporal and spatial regulation of gene expression and silencing. How altered epigenetic mechanisms regulate the pathophysiological function of cells, tissues, and ultimately entire organs following IR exposure remains to be investigated in detail. Radiation-induced epigenetic processes are particularly critical for immature cell populations such as tissue-specific stem and progenitor cells during development and differentiation of organ tissues. Genome-wide patterns of DNA and histone modifications are established cell types-specifically during the development and differentiation of organ tissues but can also be fundamentally altered in adult organism by stress responses, such as radiation-induced DNA damage. Following IR exposure, epigenetic factors are not always fully restored to their original state, resulting in epigenetic dysfunction that causes cells to lose their original identity and function. Moreover, severe radiation-induced DNA damage can induce premature senescence of cells in complex tissues, which ultimately leads to signs of aging and age-related diseases such as cancer. In this work, we provide an overview of the most important epigenetic changes following IR exposure and their pathophysiological significance for the development of acute and chronic radiation reactions.
电离辐射（IR）诱导各种DNA损伤的影响不仅基于遗传效应，还基于表观遗传效应。表观遗传修饰决定染色质结构和DNA可及性，从而通过单个基因或整个基因群的表达来调节细胞功能。然而，DNA修复过程对局部染色质结构和整体核结构恢复的影响仍未得到充分理解。在多细胞生物中，表观遗传机制通过对基因表达和沉默的精确时空调控来控制特定细胞类型的多种细胞功能。IR暴露后，改变的表观遗传机制如何调节细胞、组织乃至整个器官的病理生理功能仍有待详细研究。辐射诱导的表观遗传过程对于未成熟细胞群体（如器官组织发育和分化过程中的组织特异性干细胞和祖细胞）尤为关键。DNA和组蛋白修饰的全基因组模式在器官组织的发育和分化过程中以细胞类型特异性方式建立，但在成年生物体中也可能因应激反应（如辐射诱导的DNA损伤）而发生根本性改变。IR暴露后，表观遗传因子并不总是能完全恢复到原始状态，从而导致表观遗传功能障碍，使细胞失去其原始特性和功能。此外，严重的辐射诱导DNA损伤可诱导复杂组织中细胞过早衰老，最终导致衰老迹象和与年龄相关的疾病（如癌症）。在这项工作中，我们概述了IR暴露后最重要的表观遗传变化及其对急性和慢性辐射反应发展的病理生理意义。
