Razskazovskiy Y, Debije M G, Bernhard W A
Department of Biochemistry and Biophysics, University of Rochester, Rochester, New York 14642, USA.
Radiat Res. 2000 Apr;153(4):436-41. doi: 10.1667/0033-7587(2000)153[0436:drdtcd]2.0.co;2.
The radiation chemical yields of unaltered base release have been measured in three crystalline double-stranded DNA oligomers after X irradiation at 4 K. The yields of released bases are between 10 and 20% of the total free radical yields measured at 4 K. Using these numbers, we estimate that the yield of DNA strand breaks due to the direct effect is about 0.1 micromol J(-1). The damage responsible for base release is independent of the base type (C, G, A or T) and is not scavenged by anthracycline drugs intercalated in the DNA. For these reasons, reactions initiated by the hydroxyl radical have been ruled out as the source of base release. Since the intercalated anthracycline scavenges electrons and holes completely but does not inhibit base release, the possibility for damage transfer from the bases to the sugars can also be ruled out. The results are consistent with a model in which primary radical cations formed directly on the sugar-phosphate backbone react by two competing pathways: deprotonation, which localizes the damage on the sugar, and hole tunneling, which transfers the damage to the base stack. Quantitative estimates indicate that these two processes are approximately equally efficient.
在4K温度下对三种结晶双链DNA寡聚物进行X射线辐照后，测量了未改变碱基释放的辐射化学产率。释放碱基的产率在4K下测量的总自由基产率的10%至20%之间。利用这些数据，我们估计由于直接效应导致的DNA链断裂产率约为0.1微摩尔焦耳⁻¹。导致碱基释放的损伤与碱基类型（C、G、A或T）无关，并且不会被插入DNA中的蒽环类药物清除。基于这些原因，由羟基自由基引发的反应已被排除为碱基释放的来源。由于插入的蒽环类药物完全清除电子和空穴，但不抑制碱基释放，因此也可以排除损伤从碱基转移到糖的可能性。结果与一个模型一致，在该模型中，直接在糖-磷酸主链上形成的初级自由基阳离子通过两种竞争途径反应：去质子化，将损伤定位在糖上；空穴隧穿，将损伤转移到碱基堆积处。定量估计表明这两个过程的效率大致相同。
