辐射诱导损伤的传感器、早期事件及细胞死亡的全面综述
A comprehensive review of sensors of radiation-induced damage, radiation-induced proximal events, and cell death
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影响因子:8.3
分区:医学2区 / 免疫学2区
发表日期:2025 Jan
作者:
Saurabh Saini, Prajwal Gurung
DOI:
10.1111/imr.13409
摘要
辐射作为地球环境中的普遍因素，分为非电离辐射和电离辐射。非电离辐射相对无害，而电离辐射具有足够能量电离原子，破坏DNA，导致细胞损伤、突变、癌变和细胞死亡。核技术和医学应用中辐射源的广泛使用引发了全球关注，担心其引起急性和慢性疾病。电离辐射通过直接引起DNA链断裂和碱基变异，或间接通过水的辐解产生活性氧（ROS）和活性氮种（RNS），诱导DNA损伤。这些损伤触发复杂的细胞反应，包括DNA损伤识别、细胞周期停滞、DNA修复、促炎细胞因子的释放和细胞死亡。本文重点介绍辐射引起的细胞损伤机制、DNA损伤的识别及修复激活，以及先天免疫反应在损伤修复中的关键作用。特别关注模式识别受体（PRRs）及相关受体在检测损伤相关分子模式（DAMPs）和启动下游信号通路中的作用。详细讨论辐射引起的细胞死亡途径。理解这些过程对制定减轻辐射有害作用和改善治疗效果的策略至关重要。
Abstract
Radiation, a universal component of Earth's environment, is categorized into non-ionizing and ionizing forms. While non-ionizing radiation is relatively harmless, ionizing radiation possesses sufficient energy to ionize atoms and disrupt DNA, leading to cell damage, mutation, cancer, and cell death. The extensive use of radionuclides and ionizing radiation in nuclear technology and medical applications has sparked global concern for their capacity to cause acute and chronic illnesses. Ionizing radiation induces DNA damage either directly through strand breaks and base change or indirectly by generating reactive oxygen species (ROS) and reactive nitrogen species (RNS) via radiolysis of water. This damage triggers a complex cellular response involving recognition of DNA damage, cell cycle arrest, DNA repair mechanisms, release of pro-inflammatory cytokines, and cell death. This review focuses on the mechanisms of radiation-induced cellular damage, recognition of DNA damage and subsequent activation of repair processes, and the critical role of the innate immune response in resolution of the injury. Emphasis is placed on pattern recognition receptors (PRRs) and related receptors that detect damage-associated molecular patterns (DAMPs) and initiate downstream signaling pathways. Radiation-induced cell death pathways are discussed in detail. Understanding these processes is crucial for developing strategies to mitigate the harmful effects of radiation and improve therapeutic outcomes.