Nevaldine B, Longo J A, Vilenchik M, King G A, Hahn P J
Department of Radiology, State University of New York Health Science Center, Syracuse 13210.
Radiat Res. 1994 Nov;140(2):161-5.
We have used pulsed-field gel electrophoresis (PFGE) to test two hypotheses that have been proposed to explain the survival curves with shoulders which are characteristic of low-LET ionizing radiation: (1) Neutral elution studies of the induction of double-strand breaks (DSBs) have suggested that ionizing radiation might induce DSBs in a nonlinear fashion at low doses. (2) Based on analogies to enzyme kinetics, DSB repair might be saturating in the shoulder region. We quantified DSB induction and survival resulting from doses between 0 and 5 Gy spanning the shoulder region of the survival curve. We found that DSB induction was linear at all doses tested down to 0.5 Gy, the limits of sensitivity. Therefore, nonlinear DSB induction cannot account for the shape of the survival curve. To determine whether the DSB repair system was saturated in the shoulder region, we quantified the rate of DSB repair as a function of dose of X rays between 1.25 and 20 Gy. The repair of DSBs was exponential with half-times of repair constant for doses below 10 Gy, and averaged 28 min. We determined the initial rate of repair from the exponential repair kinetics for each dose. The initial rate of repair after radiation treatment increased linearly with dose up to at least 10 Gy. Therefore, saturating DSB repair cannot explain the shoulder of the survival curve.
我们已使用脉冲场凝胶电泳（PFGE）来检验两个假说，这两个假说被提出来用以解释具有低传能线密度（LET）电离辐射特征的、带有肩区的存活曲线：（1）双链断裂（DSB）诱导的中性洗脱研究表明，电离辐射在低剂量时可能以非线性方式诱导DSB。（2）基于与酶动力学的类比，DSB修复在肩区可能会达到饱和。我们对剂量在0至5 Gy之间、涵盖存活曲线肩区的DSB诱导和存活情况进行了量化。我们发现，在测试的所有低至0.5 Gy（灵敏度极限）的剂量下，DSB诱导都是线性的。因此，非线性DSB诱导无法解释存活曲线的形状。为了确定DSB修复系统在肩区是否饱和，我们对剂量在1.25至20 Gy之间的X射线照射下的DSB修复速率作为剂量的函数进行了量化。对于低于10 Gy的剂量，DSB的修复呈指数形式，修复半衰期恒定，平均为28分钟。我们根据每个剂量的指数修复动力学确定了初始修复速率。放射治疗后的初始修复速率随剂量增加至少到10 Gy时呈线性增加。因此，饱和的DSB修复无法解释存活曲线的肩区。
