Milano M T, Hu G G, Williams L D, Bernhard W A
Department of Biochemistry and Biophysics, University of Rochester, New York 14642, USA.
Radiat Res. 1998 Jul;150(1):101-14.
Electrons and holes generated in irradiated DNA migrate to stable trapping sites. Protonation and deprotonation reactions at these sites promote the trapping of electrons and holes, thereby inhibiting further migration. The extent of migration determines the final distribution of damage in irradiated DNA. In this study, electron and hole migration is investigated in a crystalline DNA hexamer intercalated with an anthracycline drug. The intercalator is no further than 2 base pairs away from any DNA base. From EPR measurements, there is no evidence of DNA-centered radicals in the irradiated DNA hexamer. The aromatic region of the anthracycline intercalator evidently sequesters most or all of the electrons and most of the holes. Further hole trapping and radical stabilization appear to occur on the anthracycline's amino sugar group, which is nestled in the minor groove of the hexamer. The relatively large yield of this proposed amino sugar radical suggests that holes generated in the DNA solvation shell migrate to the amino sugar, where they become trapped. This would be the first observation of a radical formed by the direct effect of low-dose, low-LET radiation that is trapped within the DNA helix, yet lies outside of the stacked bases. With respect to holes generated in the DNA bases at 4 K, we conclude that most, if not all, are capable of migrating to an intercalator < or = 2 base pairs away. With respect to dry electrons, we conclude that anthracycline competes effectively for electron trapping over a region of at least 2 base pairs; our experiments cannot distinguish between electron attachment to the bases followed by transfer to the intercalator and direct attachment to the intercalator.
辐照DNA中产生的电子和空穴迁移至稳定的俘获位点。这些位点处的质子化和去质子化反应促进电子和空穴的俘获，从而抑制进一步迁移。迁移程度决定了辐照DNA中损伤的最终分布。在本研究中，对插入蒽环类药物的结晶DNA六聚体中的电子和空穴迁移进行了研究。嵌入剂与任何DNA碱基的距离不超过2个碱基对。从电子顺磁共振测量结果来看，在辐照的DNA六聚体中没有以DNA为中心的自由基的证据。蒽环类嵌入剂的芳香区域显然隔离了大部分或所有电子以及大部分空穴。进一步的空穴俘获和自由基稳定似乎发生在蒽环类药物的氨基糖基团上，该基团位于六聚体的小沟中。这种推测的氨基糖自由基相对较高的产率表明，在DNA溶剂化层中产生的空穴迁移到氨基糖上并被捕获。这将是首次观察到由低剂量、低传能线密度辐射的直接效应形成的自由基被困在DNA螺旋内，但位于堆积碱基之外。关于在4K时DNA碱基中产生的空穴，我们得出结论，大多数（如果不是全部）空穴能够迁移到距离不超过2个碱基对的嵌入剂处。关于干电子，我们得出结论，蒽环类药物在至少2个碱基对的区域内有效地竞争电子俘获；我们的实验无法区分电子先附着在碱基上然后转移到嵌入剂与直接附着在嵌入剂上的情况。
