Fram R J, Kufe D W
Cancer Res. 1982 Oct;42(10):4050-3.
We have used alkaline elution analysis to determine whether strand breaks are detectable in L1210 DNA labeled during and prior to 1-beta-D-arabinofuranosylcytosine (ara-C) exposure. The results demonstrate that ara-C enhances elution of previously synthesized DNA as well as replicating DNA. ara-C induced dose-dependent strand breaks when DNA was labeled prior to drug exposure. In contrast, simultaneous exposure of cells to tritiated thymidine and drug resulted in maximal elution rates with 10(-6) M ara-C. These findings are compared to those obtained with aphidicolin, another inhibitor of DNA synthesis, which unlike ara-C is not incorporated into the DNA strand. These results suggest that both ara-C and aphidicolin increase DNA elution rates by impairing DNA synthesis. The different dose-dependent patterns during replicative DNA synthesis may result from the incorporation of ara-C in the DNA strand.
我们已使用碱性洗脱分析法来确定在暴露于1-β-D-阿拉伯呋喃糖基胞嘧啶（ara-C）期间及之前标记的L1210 DNA中是否可检测到链断裂。结果表明，ara-C增强了先前合成的DNA以及正在复制的DNA的洗脱。当在药物暴露之前标记DNA时，ara-C诱导剂量依赖性链断裂。相比之下，细胞同时暴露于氚标记的胸腺嘧啶和药物时，10(-6) M ara-C导致最大洗脱率。将这些发现与使用阿非科林（另一种DNA合成抑制剂）获得的发现进行比较，阿非科林与ara-C不同，不会掺入DNA链中。这些结果表明，ara-C和阿非科林均通过损害DNA合成来提高DNA洗脱率。复制性DNA合成过程中不同的剂量依赖性模式可能是由于ara-C掺入DNA链所致。
