The effects of 9-beta-D-arabinofuranosyladenine on the repair of DNA strand breaks in X-irradiated Ehrlich ascites tumour cells.
The effects of 9-beta-D-arabinofuranosyladenine on the repair of DNA strand breaks in X-irradiated Ehrlich ascites tumour cells.
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9-β-D-阿拉伯呋喃糖腺嘌呤对 X 射线照射的艾氏腹水肿瘤细胞 DNA 链断裂修复的影响。
DOI：
10.1080/09553008214551311
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发表时间：
1982
期刊：
影响因子：
--
通讯作者：
D. Blöcher
中科院分区：
文献类型：
--
作者：
P. Bryant;D. Blöcher
在 X 射线照射的艾氏腹水肿瘤细胞中研究了 DNA 合成抑制剂 9-β-D-阿拉伯呋喃糖腺嘌呤 (β-ara A)（一种脱氧腺嘌呤的核苷类似物）对 DNA 单链和双链断裂（ssb 和 dsb）修复的影响。使用解旋方法跟踪 ssb 的修复，并使用解旋方法和中性蔗糖离心方法测量 DSB 的修复。 β-ara A 的存在会抑制 ssb 的修复；然而，即使在高浓度下，也会发生一些修复。这表明该比例的断裂（约30%）是通过多核苷酸连接酶连接的，并且不需要插入核苷酸。 Dsb 修复受到 beta-ara A 的强烈抑制，这种抑制在高浓度下是完全的。因此，dsb 修复似乎绝对需要 DNA 聚合。照射后用β-ara A（200μmols/1、2小时）处理细胞时，dsb修复受到抑制；然而，当药物被冲走后，DSB 的修复又恢复了。 6小时后，发现β-ara A处理的细胞中比未处理的对照细胞中持续存在更多的断裂。在条件培养基中用β-ara A以120μmols/1进行X射线照射7小时，然后在不含β-ara A的新鲜培养基中处理24小时后，细胞显示出比对照细胞更高数量的残留dsb。这表明这些残留的 DSB 可能与 X 辐射培养物中添加 β-ara A 引起的杀伤效果增强有关。
The effects of the DNA synthesis inhibitor 9-beta-D-arabinofuranosyladenine (beta-ara A), a nucleoside analogue of desoxyadenine, on repair of DNA single and double strand breaks (ssb and dsb) were investigated in X-irradiated Ehrlich ascites tumour cells. Repair of ssb was followed using the unwinding method, and repair of dsb was measured with both the unwinding and the neutral sucrose centrifugation methods. Repair of ssb was inhibited in the presence of beta-ara A; however, even at high concentrations some repair took place. It is suggested that this proportion of the breaks (about 30 per cent) are joined by polynucleotide ligase, and do not require insertion of nucleotides. Dsb repair was strongly inhibited by beta-ara A, the inhibition being complete at high concentrations. It seems likely therefore that dsb repair has an absolute requirement for DNA polymerization. When cells were treated with beta-ara A (200 mumols/1, 2 hours) after irradiation dsb repair was inhibited; however, when the drug was washed away, repair of dsb returned. At 6 hours more breaks were found to have persisted in beta-ara A treated cells than in the untreated controls. Cells treated after X-irradiation with beta-ara A for 7 hours at 120 mumols/1 in conditioned medium and afterwards in fresh medium free of beta-ara A for 24 hours showed a higher number of residual dsb than control cells. It is suggested that these residual dsb may be relevant to the increased killing effect caused by adding beta-ara A to X-irradiated cultures.