Snyder R D, Lachmann P J
Merrell Dow Research Institute, Cincinnati, OH 45215.
Mutat Res. 1989 Jul;226(3):185-90. doi: 10.1016/0165-7992(89)90018-3.
The cytotoxicity, DNA-strand breaking ability, and effects on repair of X-ray-induced DNA damage by short treatments with 5-azacytidine (azaCyd) and 5-azadeoxycytidine (azadCyd) were examined in HeLa cells. azaCyd was shown to be an effective inhibitor of the repair of X-ray-induced DNA single-strand breaks whereas azadCyd did not have this effect. At high doses, both compounds also induced DNA damage by themselves. The cytotoxicity, inhibition of repair, and drug-induced DNA damage associated with azaCyd treatment were all reversed by the concurrent addition to the cells of cytidine or uridine but not by thymidine, deoxycytidine or deoxyuridine. Cytotoxicity and drug-induced strand breaks associated with azadCyd treatment were reversed to varying degrees with all nucleosides and deoxynucleosides. These results support the notion that these two antileukemic cytidine analogs may have different mechanisms of action in exerting their antiproliferative activity.
在HeLa细胞中检测了5-氮杂胞苷（azaCyd）和5-氮杂脱氧胞苷（azadCyd）短期处理对细胞毒性、DNA链断裂能力以及X射线诱导的DNA损伤修复的影响。结果表明，azaCyd是X射线诱导的DNA单链断裂修复的有效抑制剂，而azadCyd没有这种作用。在高剂量时，这两种化合物自身也会诱导DNA损伤。与azaCyd处理相关的细胞毒性、修复抑制和药物诱导的DNA损伤，在细胞中同时添加胞苷或尿苷时均可逆转，但胸腺嘧啶核苷、脱氧胞苷或脱氧尿苷则不能。与azadCyd处理相关的细胞毒性和药物诱导的链断裂，在所有核苷和脱氧核苷作用下都有不同程度的逆转。这些结果支持了这两种抗白血病胞苷类似物在发挥抗增殖活性时可能具有不同作用机制的观点。
