Bryant P E, Blöcher D
Int J Radiat Biol Relat Stud Phys Chem Med. 1982 Oct;42(4):385-94. doi: 10.1080/09553008214551311.
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.
在经X射线照射的艾氏腹水瘤细胞中，研究了脱氧腺嘌呤的核苷类似物——DNA合成抑制剂9-β-D-阿拉伯呋喃糖基腺嘌呤（β-ara A）对DNA单链和双链断裂（ssb和dsb）修复的影响。采用解旋法跟踪ssb的修复情况，并用解旋法和中性蔗糖密度离心法测定dsb的修复情况。在β-ara A存在的情况下，ssb的修复受到抑制；然而，即使在高浓度下仍有一些修复发生。据推测，这部分断裂（约30%）是由多核苷酸连接酶连接的，不需要插入核苷酸。β-ara A强烈抑制dsb的修复，在高浓度下抑制作用完全。因此，dsb修复似乎绝对需要DNA聚合作用。当细胞在照射后用β-ara A（200μmol/L，2小时）处理时，dsb的修复受到抑制；然而，当洗去药物后，dsb的修复又恢复了。在6小时时，发现经β-ara A处理的细胞中持续存在的断裂比未处理的对照细胞更多。在条件培养基中用120μmol/L的β-ara A对经X射线照射的细胞处理7小时，然后在不含β-ara A的新鲜培养基中培养24小时，结果显示这些细胞中残留的dsb数量比对照细胞多。据推测，这些残留的dsb可能与在X射线照射的培养物中添加β-ara A所导致的杀伤作用增强有关。
