ENHANCED EXPRESSION OF THYMIDINE KINASE IN HUMAN-CELLS FOLLOWING IONIZING-RADIATION
ENHANCED EXPRESSION OF THYMIDINE KINASE IN HUMAN-CELLS FOLLOWING IONIZING-RADIATION
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DOI：
10.1016/0360-3016(94)90019-1
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发表时间：
1994-09-30
影响因子：
7
通讯作者：
SAHIJDAK, WM
中科院分区：
文献类型：
--
作者：
BOOTHMAN, DA;DAVIS, TW;SAHIJDAK, WM
目的：研究电离辐射前后人体正常细胞与肿瘤细胞胸苷激酶启动子结合转录因子的激活情况。方法与材料：采用Northern blot、dot-blot和胸苷激酶酶法观察放疗前后胸苷激酶转录和酶的变化。还研究了胸苷激酶转录物在最佳诱导剂量照射后的时间表达。使用胸苷激酶启动子的95个碱基对片段（包含CCAAT盒）进行凝胶迁移转移分析，以分析转录因子的结合。结果：人肿瘤胸苷激酶转录物和酶水平高于正常细胞。相比之下，x射线激活的胸苷激酶转录因子水平在人类肿瘤细胞中与正常细胞相比没有显著差异。结论：x射线诱导胸苷激酶转录物、酶水平和转录因子升高与肿瘤细胞缺乏严格的细胞生长调节是一致的。电离辐射后胸苷激酶的诱导可用于使用卤代嘧啶的化疗策略和/或各种基因治疗策略。
Purpose: We investigated the induction of thymidine kinase transcription and enzymatic activity, and the activation of transcription factors binding to the thymidine kinase promoter, in human normal compared to tumor cells in culture before and after ionizing radiation.Methods and Materials: Northern blot, dot-blot, and thymidine kinase enzyme assays were used to observe thymidine kinase transcript and enzymatic changes before and after radiation. Temporal expression of thymidine kinase transcripts following an optimal induction dose of radiation was also studied. Gel mobility shift assays were performed using a 95-base pair fragment of the thymidine kinase promoter (containing the CCAAT box) to analyze transcription factor binding.Results: Thymidine kinase transcript and enzymatic levels were higher in human tumor compared to normal cells. In contrast, levels of x-ray-activated thymidine kinase transcription factors were not significantly different in human neoplastic compared to normal cells.Conclusion: Elevated x-ray-induced thymidine kinase transcripts, enzymatic levels, and transcription factors are consistent with the loss of stringent cell growth regulation associated with neoplastic cells. The induction of thymidine kinase following ionizing radiation may be exploited in chemotherapeutic strategies which use halogenated pyrimidines and/or in various gene therapy strategies.