Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20889, USA.
Curr Mol Pharmacol. 2009 Jan;2(1):122-33. doi: 10.2174/1874467210902010122.
The acute radiation syndrome (ARS) is defined as the signs and symptoms that occur within several months after exposure to ionizing radiation (IR). This syndrome develops after total- or partial-body irradiation at a relatively high dose (above about 1 Gy in humans) and dose rate. Normal tissue injuries induced by IR differ depending on the target organ and cell type. Organs and cells with high sensitivity to radiation include the skin, the hematopoietic system, the gut, the spermatogenic cells and the vascular system. Exposure to IR causes damage to DNA, protein, and lipids in mammalian cells, as well as increased mitochondria-dependent generation of reactive oxygen species (ROS), with subsequent cell cycle checkpoint arrest, apoptosis, and stress-related responses. DNA double strand breaks (DSBs) are a primary lethal lesion induced by IR. The cellular response to damage is complex and relies on simultaneous activation of a number of signaling networks. Among these, the activation of DNA non-homologous end-joining (NHEJ) and homologous recombination (HR), and signaling pathways containing ataxia telangiectasia mutated (ATM), play important roles. The transcription factor NFkappaB has emerged as a pro-survival actor in response to IR in ATM and p53-induced protein with a death domain (PIDD) cascades. Although radiation-induced ARS has been well documented at the clinical level, and mechanistic information is accumulating, successful prophylaxis and treatment for ARS is problematic, even with the use of supportive care and growth factors. There is a pressing need to develop radiation countermeasures that can be used both in the clinic, for small-scale incidents, and outside the clinic, in mass casualty scenarios. In this review we summarize recent information on intracellular and extracellular signaling pathways relevant to radiation countermeasure research.
急性辐射综合征（ARS）是指在暴露于电离辐射（IR）后几个月内发生的体征和症状。这种综合征发生在全身或局部照射相对高剂量（人类约 1 Gy 以上）和剂量率后。IR 引起的正常组织损伤因靶器官和细胞类型而异。对辐射敏感的器官和细胞包括皮肤、造血系统、肠道、生精细胞和血管系统。IR 会导致哺乳动物细胞中的 DNA、蛋白质和脂质受损，并增加线粒体依赖性活性氧（ROS）的产生，随后出现细胞周期检查点停滞、细胞凋亡和应激相关反应。DNA 双链断裂（DSBs）是 IR 诱导的主要致死损伤。细胞对损伤的反应是复杂的，依赖于同时激活许多信号网络。在这些信号网络中，DNA 非同源末端连接（NHEJ）和同源重组（HR）的激活，以及包含共济失调毛细血管扩张突变（ATM）的信号通路，起着重要作用。转录因子 NFkappaB 已成为 ATM 和 p53 诱导的具有死亡结构域（PIDD）的蛋白中 IR 反应的一种生存促进因子。尽管辐射诱导的 ARS 在临床水平上已有很好的记录，并且机制信息正在积累，但即使使用支持性护理和生长因子，对 ARS 的成功预防和治疗仍然是一个问题。迫切需要开发既能在临床用于小规模事件，又能在临床外大规模伤亡情况下使用的辐射对策。在这篇综述中，我们总结了与辐射对策研究相关的细胞内和细胞外信号通路的最新信息。
