RADIATION POTENTIATION BY RHODIUM COMPLEXES

铑络合物的辐射增强作用

• 批准号: 3182212
• 负责人: ROBERT C RICHMOND
• 金额: $ 13.97万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-01 至 1989-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3182212
• 关键词: Salmonella typhimurium; cell death; hypoxia; ligands; radiation genetics; radiation sensitivity; rhodium

The intent of the proposed study is to: a) determine the radiochemical mechanisms involved in the efficient radiation potentiation of S. typhimurium cell killing observed with Rh(III) monomeric complexes; b) determine the effectiveness of Rh(III) complex-induced radiation potentiation as it relates to the concentration of the Rh complexes present at time of irradiation of S. typhimurium cells; c) determine the variable extent of radiation potentiation that the Rh(III) complexes cause among irradiated bacterial strains differering in DNA repair capacity. Radiation potentiation of cell killing by Rh(III) complexes is reported for the first time. The Rh complexes are essentially nontoxic, yet achieve a degree of hypoxic cell radiation potentiation that is unequalled in the literature on metal complexes to date. The intended characterization described above will elucidate a diverse blend of radiochemical mechanisms that in some cases in part include toxic product activity and in other cases not, that include at times only reductive pathways of action and at times both oxidative and reductive pathways, that involve a diverse response to scavenging of the hydroxyl radical and the hydrated electron, and that are variably sensitive to DNA repair systems of the irradiated biological test system. The understanding of the mechanisms by which metal complexes serve as radiation sensitizers and potentiators of cell killing will be advanced by this proposed study. The potential exists for eventual use of one or more of these Rh complexes in combination with radiation therapy. Indeed, this potential is now developing with one of the Rh(III) complexes described. The steady state radiochemical mechanisms of Rh complex action will be studied by irradiating suspensions of S. typhimurium cells in: a) the presence compared to the absence of Rh complexes selected as much as possible for systematic relationships, b) hydroxyl radical scavenger; c) hydrated electron scavenger; d) catalase. DNA damage will be investigated. Rh uptake by cells will be determined by atomic absorption spectroscopy. The kinetic radiochemical mechanism of action of these Rh complexes will be studied by pulse radiolysis techniques. The bacterial systems to be used are S. typhimurium TM35 (lacks excision repair, lacks SOS repair function), S. typhimurium TM677 (excision repair deficient, contains plasmid pKM101 with the SOS repair function), and S. typhimurium TA1978 (excision repair proficient, lacks SOS repair function).

拟议研究的目的是：a)确定放射化学物质 S.有效辐射增强的机制。 Rh(III)单体络合物对小鼠细胞的杀伤作用；b) Rh(III)络合物辐射效应的测定 增强作用，因为它与存在的Rh络合物的浓度有关 在照射鼠伤寒沙门氏菌细胞时；c)测定变量 Rh(III)络合物引起的辐射增强程度 受辐射的细菌菌株在DNA修复能力上存在差异。 报道了Rh(III)络合物对细胞杀伤的辐射增强作用。 第一次。Rh络合物基本上是无毒的，但实现了 缺氧细胞辐射增强的程度是在 迄今为止有关金属络合物的文献。预期的角色定位 上面的描述将阐明不同的放射化学机制的混合 在某些情况下，部分包括有毒产品活动，在其他情况下 情况不是这样的，有时只包括还原的行动路径和在 氧化和还原途径的时间，涉及不同的 对清除羟基自由基和水合电子的反应， 对受辐射的人的DNA修复系统有不同程度的敏感 生物测试系统。对金属的作用机理的理解 络合物作为细胞杀伤的辐射增敏剂和增强剂 将通过这项拟议的研究来推进。最终存在这样的可能性 将一个或多个这些Rh络合物与辐射结合使用 心理治疗。事实上，这种潜力现在正在与Rh(III)之一一起发展 所描述的复合体。 Rh络合作用的稳态放化机理将是 通过照射鼠伤寒沙门氏菌细胞悬浮液进行研究：a) 存在与不存在所选择的Rh络合物的比较 可能存在系统关系，b)羟基自由基清除剂；c) 水合电子清除剂；d)过氧化氢酶。DNA损伤将是 调查过了。细胞对Rh的摄取将通过原子吸收来确定 光谱学。这些Rh的动力学放化作用机理 络合物将用脉冲辐解技术进行研究。细菌 使用的系统是鼠伤寒沙门氏菌TM35(缺乏切除修复，缺乏 SOS修复功能)，鼠伤寒沙门氏菌TM677(切除修复缺陷， 含有具有SOS修复功能的质粒pKM101)和鼠伤寒沙门氏菌 TA1978(精通切除修复，缺乏SOS修复功能)。