Department of Nuclear Science and Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing 211106, China.
Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215000, China.
Int J Mol Sci. 2019 Oct 8;20(19):4963. doi: 10.3390/ijms20194963.
Among the radicals (hydroxyl radical (OH), hydrogen atom (H), and solvated electron (e)) that are generated via water radiolysis, OH has been shown to be the main transient species responsible for radiation damage to DNA via the indirect effect. Reactions of these radicals with DNA-model systems (bases, nucleosides, nucleotides, polynucleotides of defined sequences, single stranded (ss) and double stranded (ds) highly polymeric DNA, nucleohistones) were extensively investigated. The timescale of the reactions of these radicals with DNA-models range from nanoseconds (ns) to microseconds (µs) at ambient temperature and are controlled by diffusion or activation. However, those studies carried out in dilute solutions that model radiation damage to DNA via indirect action do not turn out to be valid in dense biological medium, where solute and water molecules are in close contact (e.g., in cellular environment). In that case, the initial species formed from water radiolysis are two radicals that are ultrashort-lived and charged: the water cation radical (HO) and prethermalized electron. These species are captured by target biomolecules (e.g., DNA, proteins, etc.) in competition with their inherent pathways of proton transfer and relaxation occurring in less than 1 picosecond. In addition, the direct-type effects of radiation, i.e., ionization of macromolecule plus excitations proximate to ionizations, become important. The holes (i.e., unpaired spin or cation radical sites) created by ionization undergo fast spin transfer across DNA subunits. The exploration of the above-mentioned ultrafast processes is crucial to elucidate our understanding of the mechanisms that are involved in causing DNA damage via direct-type effects of radiation. Only recently, investigations of these ultrafast processes have been attempted by studying concentrated solutions of nucleosides/tides under ambient conditions. Recent advancements of laser-driven picosecond electron accelerators have provided an opportunity to address some long-term puzzling questions in the context of direct-type and indirect effects of DNA damage. In this review, we have presented key findings that are important to elucidate mechanisms of complex processes including excess electron-mediated bond breakage and hole transfer, occurring at the single nucleoside/tide level.
在水辐射分解产生的自由基（羟基自由基 (OH)、氢原子 (H) 和溶剂化电子 (e)）中，OH 已被证明是通过间接效应导致 DNA 辐射损伤的主要瞬变物质。这些自由基与 DNA 模型系统（碱基、核苷、核苷酸、具有明确定义序列的多核苷酸、单链 (ss) 和双链 (ds) 高分子 DNA、核组蛋白）的反应已被广泛研究。这些自由基与 DNA 模型的反应在环境温度下的时间尺度从纳秒 (ns) 到微秒 (µs) 不等，受扩散或激活控制。然而，在稀溶液中进行的那些模拟间接作用导致 DNA 辐射损伤的研究结果在密集的生物介质中并不成立，在生物介质中，溶质和水分子紧密接触（例如，在细胞环境中）。在这种情况下，水辐射分解形成的初始物质是两种超短寿命和带电的自由基：水阳离子自由基 (HO) 和预热电子。这些物质与它们在不到 1 皮秒内发生的固有质子转移和弛豫途径竞争，被靶生物分子（例如 DNA、蛋白质等）捕获。此外，辐射的直接类型效应，即大分子的电离加上离化附近的激发，变得很重要。由电离产生的空穴（即不成对的自旋或阳离子自由基位点）在 DNA 亚基中经历快速自旋转移。探索上述超快过程对于阐明我们对通过辐射的直接类型效应导致 DNA 损伤的机制的理解至关重要。直到最近，通过在环境条件下研究核苷/盐的浓缩溶液，才尝试研究这些超快过程。激光驱动的皮秒电子加速器的最新进展为解决直接和间接 DNA 损伤效应方面的一些长期困惑问题提供了机会。在这篇综述中，我们介绍了阐明重要发现，这些发现对于阐明包括过剩电子介导的键断裂和空穴转移在内的复杂过程的机制很重要，这些过程发生在单个核苷/盐水平。
