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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >Evidence of a reduced DNA topoisomerase II mRNA expression after ionizing radiation.
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Evidence of a reduced DNA topoisomerase II mRNA expression after ionizing radiation.

机译:电离辐射后DNA拓扑异构酶II mRNA表达降低的证据。

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DNA topoisomerase II (top2) is a nuclear enzyme which resolves the topological constraints during DNA metabolism and is the target of some of the most active drugs used in cancer chemotherapy. Top2 is regulated both transcriptionally and post-transcriptionally and its expression is coupled to cell cycle position. To explore the regulation of top2 after DNA damage, we studied the behavior of cell lines of the National Cancer Institute Anticancer Drug Screen, previously characterized for p53 status, in response to ionizing radiation. The kinetics of top2 mRNA expression were measured using quantitative hybridization. A profound and transient decrease of top2 mRNA after irradiation was detected within four hours in 30% of the 25 cell lines tested. This transient top2 decrease in mRNA expression occurred independently of the p53 status of the cell lines and was not associated with increased apoptotic DNA fragmentation. This observation indicates that a transient decrease in top2 mRNA expression may occur after DNA damage and suggests the need for preferential schedule when planning the use of top2 inhibitors with ionizing radiation during combined radio-chemotherapy treatments.
机译:DNA拓扑异构酶II(top2)是一种核酶,可解决DNA代谢过程中的拓扑限制,是某些用于癌症化疗的活性最高的药物的靶标。 Top2在转录和转录后均受调控,其表达与细胞周期位置相关。为了探索DNA损伤后top2的调控,我们研究了美国国家癌症研究所抗癌药物筛选细胞系的行为,该细胞系先前针对p53状态进行了表征,可响应电离辐射。使用定量杂交测量top2 mRNA表达的动力学。在测试的25个细胞系中,有30%在辐射后4小时内检测到top2 mRNA的急剧而短暂的下降。 mRNA表达的这种瞬时top2降低与细胞系的p53状态无关,并且与凋亡DNA片段化增加无关。该观察结果表明,DNA损伤后,top2 mRNA表达可能会短暂下降,并提示在计划联合放射化学疗法治疗中使用电离辐射的top2抑制剂使用时需要优先安排。

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