Klimczak U, Ludwig D C, Mark F, Rettberg P, Schulte-Frohlinde D
Max-Planck-Institut für Strahlenchemie, Mülheim a.d. Ruhr, Germany.
Int J Radiat Biol. 1993 Nov;64(5):497-510. doi: 10.1080/09553009314551711.
We have measured the yields of strand break formation and biological inactivation as a function of OH scavenger concentration for 60Co gamma-irradiated pBR322 plasmid and M13mp9 RF phage DNA. The yields of single-strand breaks (ssbs), double-strand breaks formed proportionally to dose (alpha dsbs), and lethal damage (LD) decrease with increasing scavenging capacity sigma, their ratios remaining approximately constant up to sigma approximately 10(8) s-1. On a double-logarithmic plot the yields decrease linearly with sigma in parallel lines. At higher scavenging capacities, the yields, while still decreasing, level off to a different extent. Our results for the yields of ssbs and alpha dsbs confirm those of Krisch et al. (1991) using SV40 DNA. The data were analysed assuming that DNA damage is brought about by OH radicals, and a non-scavengeable portion arising from the direct radiation effect. Using a model based on non-homogeneous scavenging kinetics, the dependence on scavenging capacity of the ssb yield could be quantitatively accounted for. From the scavenging dependence of the yield of dsbs which are formed quadratically with dose (beta dsbs) and which are the result of two independent ssbs within a critical distance h, a value of about 13 basepairs was obtained for h. The parallel decrease in the yield of ssbs and alpha dsbs with scavenging capacity was rationalized in terms of the Siddiqi-Bothe mechanism (Siddiqi and Bothe 1987). The efficiency of this mechanism was found to be approximately 0.01. From the analysis of the LD yields it was shown that up to sigma approximately 10(8) s-1, inactivation is predominantly due to single OH radicals which lead to LD with an efficiency of 0.12 per OH-induced ssb. At higher scavenging capacities, a non-scavengeable spur effect similar to the locally multiply damaged sites mechanism of Ward (1988) mainly contributes to LD.
我们已经测量了经60Coγ射线辐照的pBR322质粒和M13mp9 RF噬菌体DNA中，链断裂形成产率和生物失活率与羟基清除剂浓度的函数关系。单链断裂（ssbs）、与剂量成比例形成的双链断裂（αdsbs）和致死损伤（LD）的产率随清除能力σ的增加而降低，在σ约为10(8) s-1之前，它们的比率大致保持恒定。在双对数图上，产率随σ呈平行线线性降低。在更高的清除能力下，产率虽然仍在下降，但会在不同程度上趋于平稳。我们关于ssbs和αdsbs产率的结果证实了Krisch等人（1991年）使用SV40 DNA所得到的结果。分析数据时假设DNA损伤是由羟基自由基引起的，并且存在由直接辐射效应产生的不可清除部分。使用基于非均匀清除动力学的模型，可以定量解释单链断裂产率对清除能力的依赖性。从与剂量二次方相关形成的双链断裂（βdsbs）的清除依赖性出发，βdsbs是在临界距离h内两个独立单链断裂的结果，由此得到h的值约为13个碱基对。单链断裂和αdsbs产率随清除能力的平行降低，根据Siddiqi - Bothe机制（Siddiqi和Bothe，1987年）得到了合理的解释。发现该机制的效率约为0.01。通过对致死损伤产率的分析表明，在σ约为10(8) s-1之前，失活主要是由于单个羟基自由基导致的，每个由羟基诱导的单链断裂导致致死损伤的效率为0.12。在更高的清除能力下，类似于Ward（1988年）的局部多重损伤位点机制的不可清除的刺突效应主要导致致死损伤。
