Snyder R D
Mutat Res. 1984 Mar-Apr;131(3-4):163-72. doi: 10.1016/0167-8817(84)90057-9.
The effects of hydroxyurea (HU) on the DNA-excision repair process in human cells has been systematically examined. It is demonstrated that HU induces DNA single-strand break accumulation in a dose-dependent fashion in ultraviolet-irradiated and MMS-treated confluent but not log-phase fibroblasts and that these breaks are clearly the consequence of the inhibition by HU of the enzyme, ribonucleotide reductase. The breaks form rapidly, are stable for at least 10 h and largely disappear by 20 h. The production of these DNA-strand breaks is antagonized by a combined treatment of 10 microM deoxyadenosine, deoxycytidine and deoxyguanosine whereas thymidine potentiates strand-break formation at low HU concentrations. It is also confirmed that HU, while inhibiting replicative synthesis has no apparent inhibitory effect on unscheduled DNA synthesis (UDS) although the increased uptake of labeled DNA precursors into HU-treated cells makes it difficult to assess the actual effects on the repair-synthetic process. Analysis of the effects of HU on deoxynucleoside triphosphate pool levels and the demonstration of the failure of the HU block to replicative synthesis to be reversed by high (1 mM) concentrations of added deoxynucleosides lend support to the notion of compartmentalized dNTP pools for repair and replication.
已系统研究了羟基脲（HU）对人类细胞中DNA切除修复过程的影响。结果表明，HU在紫外线照射和丝裂霉素C处理的汇合期而非对数期成纤维细胞中以剂量依赖方式诱导DNA单链断裂积累，并且这些断裂显然是HU抑制核糖核苷酸还原酶所致。这些断裂迅速形成，至少10小时内稳定，20小时时基本消失。10微摩尔脱氧腺苷、脱氧胞苷和脱氧鸟苷联合处理可拮抗这些DNA链断裂的产生，而胸苷在低HU浓度下可增强链断裂形成。还证实，HU虽然抑制复制性合成，但对非预定DNA合成（UDS）没有明显抑制作用，尽管标记的DNA前体进入HU处理细胞的摄取增加，使得难以评估对修复合成过程的实际影响。对HU对脱氧核苷三磷酸池水平的影响分析以及高浓度（1毫摩尔）添加脱氧核苷不能逆转HU对复制性合成的阻断，这支持了修复和复制的dNTP池分区的观点。
