Radiation Combined Injury: DNA Damage, Apoptosis, and Autophagy.
Radiation Combined Injury: DNA Damage, Apoptosis, and Autophagy.
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DOI：
10.4247/am.2010.aba004
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发表时间：
2010-04-30
期刊：
影响因子：
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通讯作者：
Gorbunov, Nikolai V
中科院分区：
文献类型：
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作者：
Kiang, Juliann G;Garrison, Bradley R;Gorbunov, Nikolai V
辐射复合伤是指电离辐射暴露与其他创伤或生理损伤的复合。我们今天面临的辐射威胁范围包括从个人辐射暴露到恐怖主义核事件造成的大规模伤亡的一切，其中许多暴露情景包括额外创伤的可能性。放射复合伤可使靶器官和细胞增敏，加重急性放射综合征。对联合损伤高度敏感的器官和细胞是皮肤、造血系统、胃肠道、生精细胞和血管系统。在其众多效应中，辐射联合损伤导致淋巴细胞、巨噬细胞、中性粒细胞、血小板、干细胞和组织完整性的减少; iNOS/NF-κ B/NF-IL6和p53/Bax通路的激活;以及DNA单链和双链断裂、TLR信号传导、细胞因子浓度、细菌感染和细胞色素c从线粒体释放到细胞质的增加。这些改变导致细胞凋亡和自噬，并因此增加死亡率。迫切需要了解更多关于身体对复合损伤的反应，以便能够制定有效的对策，因为目前很少存在。在这篇综述中，我们总结了什么是已知的联合损伤如何修改辐射反应，特别强调DNA损伤/修复，信号转导通路，细胞凋亡和自噬。我们还描述了目前和未来的对策有关的治疗和预防复合伤。
Radiation combined injury is defined as an ionizing radiation exposure received in combination with other trauma or physiological insults. The range of radiation threats we face today includes everything from individual radiation exposures to mass casualties resulting from a terrorist nuclear incident, and many of these exposure scenarios include the likelihood of additional traumatic injury. Radiation combined injury sensitizes target organs and cells and exacerbates acute radiation syndrome. Organs and cells with high sensitivity to combined injury are the skin, the hematopoietic system, the gastrointestinal tract, spermatogenic cells, and the vascular system. Among its many effects, radiation combined injury results in decreases in lymphocytes, macrophages, neutrophils, platelets, stem cells, and tissue integrity; activation of the iNOS/NF-kappaB/NF-IL6 and p53/Bax pathways; and increases in DNA single and double strand breaks, TLR signaling, cytokine concentrations, bacterial infection, and cytochrome c release from mitochondria to cytoplasm. These alterations lead to apoptosis and autophagy and, as a result, increased mortality. There is a pressing need to understand more about the body's response to combined injury in order to be able to develop effective countermeasures, since few currently exist. In this review, we summarize what is known about how combined injury modifies the radiation response, with a special emphasis on DNA damage/repair, signal transduction pathways, apoptosis, and autophagy. We also describe current and prospective countermeasures relevant to the treatment and prevention of combined injury.