低剂量超辐射敏感与诱导辐射抗性的研究进展

THE ADVANCES OF RESEARCH ON HYPERRADIATION SENSITIVITY AND INDUCED RADIORESISTANCE

低剂量超辐射敏感(HRS)和诱导辐射抗性(IRR)是辐射生物学的两个重要现象,研究这两个现象发生的机理对于辐射保护、控制肿瘤发生、研制新的功能材料具有重要的意义。辐射产生的DNA双链断裂(DNA double-strand breaks,DSBs)是辐射诱导细胞失活的主要损伤形式。对DSBs不能进行修复或者不能进行正确的重新连接是引起细胞死亡的主要原因。与DNA合成前期(first gap phase,G1期)和DNA合成期(synthetic phase,S期)相比,HRS在DNA合成后期(second gap phase,G2期)的表现非常明显。HRS和IRR之间相互转换调控的机制可能是G2期细胞中的一部分存在一个激活过程的发生。DNA损伤修复机制在HRS/IRR过程中发挥了重要作用。在低于20cGy的剂量条件下,细胞产生效率较低的损伤效应,细胞死亡迅速增加,低剂量超辐射敏感现象(HRS)出现;在高于20cGy的条件下,辐射造成DNA双链断裂,这些DSB本身或者由辐射引起的DNA变化激活了ATM(ataxia telangiectasia mutated),G2期专有的检测点被激活,细胞周期在G2期停顿下来,激活的G2期专有的检测点促进对DNA进行修复,提高了细胞的存活率,此时,诱导辐射抗性(IRR)出现。尽管这些结果使人们对HRS/IRR有了一个比较清晰地了解,目前仍然存在着一些关键问题有待解决。例如,为什么有些细胞系表现HRS/IRR现象,而有些细胞系不表现HRS/IRR现象;细胞中是否存在针对单一剂量的突变的HRS/IRR等。这些问题可能是将来重要的研究方向。

Low dose hyperradiation sensitivity （HRS） and induced radioresistance （IRR） are two important phenoma in radiobiology. Illustrating the mechanism of HRS/IRR is important to radiation protection, tumor control and creation new functional materials. Radiation-induced DNA double-strand breaks （DSBs） is primer lesions in radiation-induced inactivation, and failure repair of （or misrepair of） DSBs is a prime cause of cell death. Low-dose hyperradiation sensitivity is more prominent in G2 phase cells compared with cells in G1 or S phase. The mechanism regulating the transition between HRS and IRR is likely to be due to an active process occurring in a small fraction of G2-phase cells. DNA repair plays an important role during HRS/IRR. When the radiation dose was lower than 20 cGy, radiation led to less efficient damage response （HRS）. When the dose was higher than 20cGy, DNA double strands broke. ATM and G2 phase specific checkpoint were activated. Cell cycle was arrested. DNA repair and cell survival were promoted, IRR appeared at this time. Although lots of results had been got, many problems were still remained. For example, why some cell lines had HRS/IRR, while others not; whether there was mutated HRS/IRR corresponding to single dose or not. These problems are likely to be the future research directions.