RADIATION INDUCED DNA DAMAGE AS A FUNCTION OF HYDRATION

描述：染色体内的DNA是 了解电离辐射对细胞的影响。类型和 DNA中产生的大量辐射诱导损伤是由 DNA直接电离产生的自由基的TH反应 (直接作用)以及DNA与形成的自由基的反应 在周围的环境中。在这种环境下，辐射 散装水和与DNA紧密结合的水分子 造成很大比例的DNA损伤。有证据表明，这些紧密地 结合水分子可以，1)构成水的很大一部分 围绕着细胞内的DNA，以及2)有助于辐射诱导的DNA 损伤主要是通过转移缺电子中心和 从这个水层到DNA的电子(准直接效应)； 一种不同于诱导DNA损伤的机制 由于散装水(如Ho、Eaq-)的照射。DNA的比例 由准直接效应和辐射引起的损伤 散装水将根据DNA构象的变化、 水合水和自由基清除作用，可以通过 金属、多胺和组蛋白与DNA的结合。自.以来 水合水损伤DNA的机理与水合水不同 散装水，完全依赖于清理的干预性策略 羟基自由基用来修饰DNA损伤在细胞中的成功可能有限。 这项建议的目标是确定机制和程度 与DNA紧密结合的水对此有贡献 辐射引起的DNA损伤。需要检验的假设是 辐射会对这些紧密结合的水分子造成损害 在DNA损伤中，这与直接的 DNA的电离，可被硫醇修饰。三种食品的种类和数量 辐射诱导的DNA损伤与剂量、水合作用、氧气的关系 将检查浓度以确定该结合的效果 金属，多胺，一种组蛋白蛋白，除了 硫醇的辐射防护作用，对辐射的贡献 直接/准直接效应和辐照污水对辐射诱导DNA的影响 损坏。从这些研究中获得的信息可能对 了解电离辐射致癌的机制， 突变和细胞致命性，以及选择或设计新的 可减少辐射或辐射的有害影响的辐射保护器 改善放射治疗的结果。

DESCRIPTION: The DNA within a chromosome is an important target in understanding the cellular effects of ionizing radiation. The types and quantities of radiation-induced damage that are produced in DNA result from th reactions of radicals generated from the direct ionization of the DNA (direct effect) and from the reactions of the DNA with free radicals formed in the surrounding environment. Within this environment, irradiation of bulk water an the water molecules that are tightly bound to DNA contribute to a large proportion of DNA damage. Evidence suggests that these tightly bound water molecules can, 1) comprise a large portion of the water that surrounds intracellular DNA, and 2) contribute to radiation-induced DNA damage primarily via the transfer of electron-deficient centers and electrons from this water layer to the DNA (quasi-direct effect); a mechanism that is different from the induction of DNA damage that is derived from the irradiation of bulk water (e.g. HO.,eaq-). The proportion of DNA damage that is derived from the quasi-direct effect and the irradiation of bulk water will vary depending on changes in DNA conformation, alteration of hydration water, and radical scavenging effects that can be mediated through the binding of metals, polyamines, and histone proteins to DNA. Since the mechanism for damaging DNA is different for the hydration water than for bulk water, interventional strategies that exclusively rely on scavenging hydroxyl radicals to modify DNA damage may have limited success in cells. It is the objective of this proposal to determine the mechanism and extent to which the water that is tightly bound to the DNA contributes to radiation-induced DNA damage. The hypothesis to be tested is that radiation-induced damage in these tightly bound water molecules can result in DNA damage that is indistinguishable from that caused by the direct ionization of DNA and modifiable by thiols. The types and quantities of radiation-induced DNA damage as a function of dose, hydration, oxygen concentration will be examined to ascertain the effect of that the binding of metals, polyamines, an histone proteins, in additional to the radioprotective effects of thiols, has on the contribution of the direct/quasi-direct effect and irradiated bilk wate on radiation-induced DNA damage. Information derived from these studies may be important for understanding the mechanisms by which ionizing radiation causes cancer, mutations, and cell lethality, and selecting or designing new radioprotectors that may reduce the deleterious effects of radiation or improv the outcome of radiotherapy.