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RADIATION POTENTIATION BY RHODIUM COMPLEXES

铑络合物的辐射增强作用

基本信息

批准号：
3182214
负责人：
ROBERT C RICHMOND
金额：
$ 13.57万
依托单位：
DARTMOUTH COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-09-01 至 1990-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3182214
关键词：
Salmonella typhimurium cell death hypoxia ligands radiation genetics radiation sensitivity rhodium

项目摘要

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）确定放射化学机制参与了有效的辐射增强S。用Rh（III）单体络合物观察到鼠伤寒杆菌细胞杀伤; B）测定Rh（III）络合物诱导辐射的有效性增强作用，因为它与存在的Rh络合物的浓度有关在S.鼠伤寒沙门氏菌细胞; c）确定变量 Rh（III）络合物引起的辐射增强程度，辐射过的细菌菌株在DNA修复能力方面表现出了惊人的能力。 Rh（III）络合物的细胞杀伤的辐射增强被报道为第一次 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，这是无与伦比的关于金属配合物的文献。预期特征以上所描述的将阐明放射化学机制的多样混合在某些情况下，部分包括有毒产品活动，情况并非如此，有时仅包括还原性作用途径，氧化和还原途径，涉及多种响应于羟基自由基和水合电子的清除，并且对辐射损伤的DNA修复系统敏感，生物测试系统对金属的作用机制的理解配合物作为辐射敏化剂和细胞杀伤的增强剂将通过这项研究得到推进。可能最终一种或多种这些Rh配合物与辐射结合的用途疗法事实上，这种潜力现在正在开发的Rh（III）之一，复合体描述。 Rh络合物作用的稳态放射化学机制将是通过照射S.悬浮液进行研究。鼠伤寒沙门氏菌细胞：a）与不存在Rh络合物相比，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损伤将是研究了细胞对Rh的吸收将通过原子吸收测定谱这些Rh的动力学放射化学作用机制复合物将通过脉冲辐解技术进行研究。细菌使用的系统是S。鼠伤寒TM 35（缺乏切除修复，缺乏 SOS修复功能）、S.鼠伤寒TM 677（切除修复缺陷，含有具有SOS修复功能的质粒pKM 101），和S.鼠伤寒 TA 1978（切除修复熟练，缺少SOS修复功能）。