THE ROLE OF CELLULAR GLUTATHIONE IN RESPONSE OF TUMOR CELLS TO RADIATION AND DRUGS

THE ROLE OF CELLULAR GLUTATHIONE IN RESPONSE OF TUMOR CELLS TO RADIATION AND DRUGS
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细胞谷胱甘肽在肿瘤细胞对辐射和药物的反应中的作用

DOI:
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发表时间:
1986
期刊:
影响因子:
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通讯作者:
E. Epp
E. Epp
中科院分区:
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文献类型:
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作者:
J. Biaglow;M. Varnes;E. P. Clark;E. Epp

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解释所观察到的氧或亲电子药物对体外照射的缺氧细胞的放射增敏作用的最著名的模型是“根本修复”模型(1-3)。该模型指出,辐射诱导的自由基产生的临界分子(如DNA)经历与氧化物质如氧或其它亲电子试剂的竞争性反应(例如,米索硝唑)导致损伤“固定”,随后细胞死亡(图1),或与还原性物质,例如非蛋白质硫醇(NPSH),导致损伤“修复”(可能通过氢原子捐赠),随后是持续的细胞活力。支持这个模型来自脉冲辐解技术。对于简单分子,分子氧与自由基的反应基本上以扩散控制的速率发生,无论是自由基加成还是电子转移,其发生频率都较低(4,5)。自由基固定的速率常数与修复的速率常数之比在200-1000的范围内;对于GSH存在下的poly-U和溶液中的转化DNA,其恒定在约200(6)。
The best known model to explain the observed radiosensit izing actions of oxygen or electron affinic drugs on hypoxic cells irradiated in vitro is that of “radical repair” (1–3). The model states that radiation-induced radicals produced in critical molecules (like DNA) undergo competitive reactions either with oxidizing species, such as oxygen or other electron affinic agents (e.g. misonidazole) leading to damage “fixation” followed by cell death (Figure 1), or with reducing species, such as non-protein thiols (NPSH) leading to damage “repair” (perhaps through hydrogen atom donation) followed by continued cell viability. Support for this model comes from pulse radiolysis techniques. For simple molecules the reactions of molecular oxygen with free radicals occur at essentially diffusion controlled rates, both for radical addition or electron transfer which occurs less frequently (4, 5). The ratio of the rate constant for radical fixation relative to that for repair is in the range of 200–1000; it is constant at about 200 for both poly-U in the presence of GSH and for transforming DNA in solution (6).
新合成的缺氧介导药物作为放射增敏剂和细胞毒剂。
DOI: 10.1016/0360-3016(82)90388-1
发表时间: 1982
期刊: International journal of radiation oncology, biology, physics
影响因子: --
作者:
Astor,M;Hall,EJ;Biaglow,JE;Parham,JC
通讯作者: Parham,JC
DOI: 10.1016/0006-2952(84)90290-9
发表时间: 1984
影响因子: 5.8
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Varnes,ME;Tuttle,SW;Biaglow,JE
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DOI: 10.1016/0360-3016(82)90717-9
发表时间: 1982
期刊: International journal of radiation oncology, biology, physics
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缺氧细胞放射增敏药物对细胞氧利用的影响。
DOI: 10.1016/0163-7258(80)90084-4
发表时间: 1980
影响因子: 13.5
作者:
Biaglow,JE
通讯作者: Biaglow,JE
邻位取代的 4- 和 5-硝基咪唑的放射增敏和细胞毒性特性:NPSH 反应性的作用。
DOI: 10.1016/0360-3016(82)90649-6
发表时间: 1982
期刊: International journal of radiation oncology, biology, physics
影响因子: --
作者:
Astor,M;Hall,EJ;Martin,J;Flynn,M;Biaglow,J;Parham,JC
通讯作者: Parham,JC