Spitz Douglas R, Azzam Edouard I, Li Jian Jian, Gius David
B180 Medical Laboratories, Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa 52242, USA.
Cancer Metastasis Rev. 2004 Aug-Dec;23(3-4):311-22. doi: 10.1023/B:CANC.0000031769.14728.bc.
Exposure of eukaryotic cells to ionizing radiation (IR) results in the immediate formation of free radicals that last a matter of milliseconds. It has been assumed that the subsequent alterations in multiple intracellular processes following irradiation is due to the initial oxidative damage caused by these free radicals. However, it is becoming increasingly clear that intracellular metabolic oxidation/reduction (redox) reactions can be affected by this initial IR-induced free radical insult and may remain perturbed for minutes, hours, or days. It would seem logical that these cellular redox reactions might contribute to the activation of protective or damaging processes that could impact upon the damaging effects of IR. These processes include redox sensitive signaling pathways, transcription factor activation, gene expression, and metabolic activities that govern the formation of intracellular oxidants and reductants. The physiological manifestations of these radiation-induced alterations in redox sensitive processes have been suggested to contribute to adaptive responses, bystander effects, cell cycle perturbations, cytotoxicity, heat-induced radiosensitization, genomic instability, inflammation, and fibrosis. While a great deal is known about the molecular changes associated with the initial production of free radicals at the time of irradiation, the contribution of perturbations in redox sensitive metabolic processes to biological outcomes following exposure to IR is only recently becoming established. This review will focus on evidence supporting the concept that perturbations in intracellular metabolic oxidation/reduction reactions contribute to the biological effects of radiation exposure as well as new concepts emerging from the field of free radical biology that may be relevant to future studies in radiobiology.
真核细胞暴露于电离辐射（IR）会立即产生持续数毫秒的自由基。人们一直认为，辐射后细胞内多个过程的后续变化是由这些自由基引起的初始氧化损伤所致。然而，越来越清楚的是，细胞内代谢氧化/还原（氧化还原）反应会受到这种初始IR诱导的自由基损伤的影响，并且可能在数分钟、数小时或数天内持续受到干扰。这些细胞氧化还原反应可能有助于激活可能影响IR损伤效应的保护或损伤过程，这似乎是合乎逻辑的。这些过程包括氧化还原敏感信号通路、转录因子激活、基因表达以及控制细胞内氧化剂和还原剂形成的代谢活动。这些辐射诱导的氧化还原敏感过程变化的生理表现被认为有助于适应性反应、旁观者效应、细胞周期扰动、细胞毒性、热诱导放射增敏、基因组不稳定、炎症和纤维化。虽然人们对辐射时与自由基初始产生相关的分子变化了解很多，但氧化还原敏感代谢过程的扰动对IR暴露后生物学结果的贡献直到最近才得以确立。本综述将聚焦于支持以下概念的证据：细胞内代谢氧化/还原反应的扰动会导致辐射暴露的生物学效应，以及自由基生物学领域中可能与未来放射生物学研究相关的新概念。
