The adaptive response in radiobiology: Evolving insights and implications
The adaptive response in radiobiology: Evolving insights and implications
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DOI：
10.2307/3433927
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发表时间：
1998-02-01
影响因子：
10.4
通讯作者：
Wolff, S
中科院分区：
文献类型：
--
作者：
Wolff, S
第一个定期重复的实验表明，非常低剂量的电离辐射，就像非常低剂量的化学剂一样，可以诱导细胞更好地科普随后的高剂量照射的机制，这是在人类淋巴细胞培养物中诱导染色体畸变的实验。如果已经暴露于非常低剂量（1 c戈伊）的X射线的细胞随后暴露于相对高剂量（1戈伊），则诱导大约一半的染色体断裂。随后的实验表明，这种对低剂量的适应性反应需要一定的最低剂量才能活跃起来;只在相对较小的剂量窗口内发生;依赖于剂量率;并取决于受照射的人或动物的遗传构成，有些人或动物没有反应。进一步表明，对低剂量预暴露的反应不是瞬时的，而是需要大约4至6小时才能完全活跃，如果在此期间蛋白质合成受到抑制，一种必需的蛋白质（酶）被诱导。事实上，随后的二维凝胶电泳实验显示，在1至2 cGy照射的细胞中出现了新的蛋白质。因此，低剂量辐射诱导的适应归因于诱导一种新的有效的染色体断裂修复机制，该机制在高剂量照射时是活跃的，将导致较少的残留损伤。一系列实验加强了这一假设，其中发现聚（ADP-核糖）聚合酶（一种与DNA链断裂重新连接有关的酶）的抑制剂可以阻止适应性反应。虽然这一现象在细胞系统中已经得到很好的证实，但它在确定电离辐射对人类的风险方面是否有任何用处仍然是个问题。现在已经进行了较新的实验，研究这种效应的机制，以及这种效应是否会表现为减少诱发癌症的数量和辐射引起的死亡率。限制性内切酶的实验现在表明，DNA中的双链断裂可以触发适应性事件。此外，关于全身受照射小鼠存活率的初步实验表明，多次暴露于低适应剂量可对存活率产生深远影响，其他实验表明，适应可影响受照射小鼠胸腺淋巴瘤的诱发。因此，适应性反应背后的最初实验似乎已导致全世界为了解其背后的基本机制而作出了积极努力，这一努力的动机是，既希望了解反应背后的基本细胞生物学，也希望看到这种现象确实影响对低水平辐射照射风险的估计。
The first of the regularly reproducible experiments to show that very low doses of ionizing radiation, like very low doses of chemical agents, could induce mechanisms whereby cells become better fit to cope with subsequent exposures to high doses were carried out on the induction of chromosome aberrations in cultures of human lymphocytes. if cells that had been exposed to a very low dose (1 cGy) of X rays were subsequently exposed to a relatively high dose (1 Gy), approximately half as many chromosome breaks were induced. Subsequent experiments showed that this adaptive response to low doses requires a certain minimal dose before it becomes active; occurs only within a relatively small window of dose; is dose-rate dependent; and depends on the genetic constitution of the people or animals exposed, with some being unresponsive. It was further shown that the response to the low-dose preexposure was not instantaneous but took approximately 4 to 6 hr to become fully active, and could be prevented if during this period protein synthesis was inhibited, i.e., a necessary protein (enzyme) was being induced. In fact, subsequent experiments with two-dimensional gel electrophoresis showed new proteins in cells irradiated with 1 to 2 cGy. The adaptation induced by low doses of radiation was therefore attributed to the induction of a novel efficient chromosome break repair mechanism that ii active at the time of challenge with high doses would lead to less residual damage. This hypothesis was strengthened by a series of experiments in which it was found that inhibitors of poly(ADP-ribose)polymerase, an enzyme implicated in DNA strand break rejoining, could prevent the adaptive response. Although the phenomenon is well established in cellular systems, it is still problematical as to whether or not it will have any utility in establishing risks of ionizing radiation to humans. Newer experiments have now been carried out on the mechanisms underlying the effect and whether or not the effect can manifest itself as a decrease in the number of induced cancers and radiation-induced mortality. Experiments with restriction enzymes now indicate that double strand breaks in DNA can be triggering events in adaptation. In addition, preliminary experiments on the survival of whole-body irradiated mice have shown that multiple exposures to low adapting doses can have profound effects on survival, and other experiments have shown that adaptation can affect the induction of thymic lymphoma in irradiated mice. It therefore appears that the initial experiments behind the adaptive response have led to a vigorous worldwide effort to understand the basic mechanisms behind it. This effort is stimulated both by a desire to understand the basic cell biology behind the response and a desire to see ii indeed this phenomenon affects the estimation of risks of low-level radiation exposure.