Relationship between DNA damage, DNA repair, metabolic state and cell lethality
Relationship between DNA damage, DNA repair, metabolic state and cell lethality
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DNA损伤、DNA修复、代谢状态和细胞致死率之间的关系
DOI：
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发表时间：
1992
影响因子：
1.7
通讯作者：
C. Wallen
中科院分区：
文献类型：
--
作者：
K. Wheeler;Robbie Hickman;G. Nelson;Sarah K. Moore;C. Wallen
不可修复的DNA损伤的诱导、错误修复的DNA损伤的积累以及竞争性生化和/或代谢过程中的不平衡的产生已被提出来解释辐射诱导的DNA损伤和细胞致死率之间的关系。理论上，关键DNA修复过程的温度依赖性应该是1）如果前两个假设是正确的，则独立于细胞杀伤的温度依赖性或与细胞杀伤的温度依赖性相同，并且2）如果第三个假设是正确的，则不同。为了测试这一点，将指数生长的大鼠9 L脑肿瘤细胞置于37°C下或在照射前在20°C下平衡3-14小时。照射细胞并使其在20°C或37°C下修复。或者，在这些温度之一下照射细胞，并立即转移到另一个温度进行修复。通过碱性洗脱技术评估DNA损伤;通过克隆形成试验评估细胞杀伤。在20°C或37°C下维持的9 L细胞维持相同量的DNA损伤，如通过碱洗脱所测量的。DNA的瞬时修复呈现出辐射后温度的速率特征。对于在20°C下平衡、照射和修复的9 L细胞，与在37°C下孵育、照射和修复的细胞中测量的相比，DNA修复的快速期的半衰期减少了1/12，缓慢期的半衰期减少了1/15。尽管DNA修复速率在20°C下显著降低，但当通过立即平板接种方案进行测定时，在20°C下平衡并照射的9 L细胞的存活率高于（p <10−4）在37°C下孵育并照射的9 L细胞。此外，在20°C下平衡和辐照，然后在辐照后立即转移到37°C的9 L细胞的存活率高于（p <10−2）任何其他延迟平板接种方案获得的存活率。因此，通过碱洗脱测量的DNA修复过程的温度依赖性不同于通过立即或延迟铺板方案测量的细胞杀伤的温度依赖性。这些数据支持这样的假设，即许多照射的9 L肿瘤细胞死亡，因为在一组竞争的生化和/或代谢过程的不平衡。
SummaryInduction of unrepairable DNA damage, accumulation of misrepaired DNA damage, and generation of imbalances in competing biochemical and/or metabolic processes have been proposed to explain the relationship between radiation-induced DNA damage and cell lethality. Theoretically, the temperature dependence of the critical DNA repair process(es) should be 1) either independent of or identical to the temperature dependence of cell killing if the first two hypotheses are correct, and 2) different if the third hypothesis is correct. To test this, exponentially growing rat 9L brain tumor cells were left at 37°C or equilibrated for 3–14 h at 20°C before irradiation. Cells were irradiated and allowed to repair at either 20°C or 37°C. Alternatively, the cells were irradiated at one of these temperatures and immediately shifted to the other temperature for repair. DNA damage was assessed by the alkaline elution technique; cell kill was assessed by a clonogenic assay. 9L cells maintained at 20°C or 37°C sustained the same amount of DNA damage as measured by alkaline elution. DNA repair instantaneously assumed the rate characteristic of the postirradiation temperature. For 9L cells equilibrated, irradiated, and repaired at 20°C, the half-time of the fast phase of the DNA repair decreased by a factor of ≈2 and the half-time of the slow phase decreased by a factor of ≈5 over that measured in cells incubated, irradiated and repaired at 37°C. Although the rate of DNA repair decreased substantially at 20°C, the survival of 9L cells that were equilibrated and irradiated at 20°C was greater (p <10−4) than those incubated and irradiated at 37°C, when assayed by an immediate plating protocol. In addition, the survival of 9L cells equilibrated and irradiated at 20°C and then shifted to 37°C immediately after irradiation was greater (p <10−2) than that obtained with any other delayed plating protocol. Thus, the temperature dependence of the DNA repair processes measured by alkaline elution was different from the temperature dependence of cell killing measured either by an immediate or delayed plating protocol. These data support the hypothesis that many irradiated 9L tumor cells die because of imbalances in sets of competing biochemical and/or metabolic processes.
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分裂和非分裂哺乳动物细胞中 DNA 修复过程的饱和。
影响因子：
3.4
作者：
Wheeler,KT;Nelson,GB
通讯作者：
Nelson,GB
肿瘤内位置对体外加热解离细胞存活的影响。
影响因子：
3.4
作者：
Wallen,CA;Norton,KL;Wheeler,KT
通讯作者：
Wheeler,KT
影响因子：
3.1
作者：
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通讯作者：
KRUUV, J
用于描述肩部生存曲线的修复饱和假设的检验。
影响因子：
3.4
作者：
Ward,JF;Limoli,CL;Calabro-Jones,PM;Aguilera,J
通讯作者：
Aguilera,J
咖啡因对 X 射线照射的 HeLa 细胞的作用。
影响因子：
3.4
作者：
Tolmach,LJ;Duncan,PG;Beetham,KL
通讯作者：
Beetham,KL