Snyder R D
Marion Merrell Dow Research Institute, Cincinnati, OH 45215.
Oncol Res. 1994;6(4-5):177-82.
The effects of treatment of HeLa cells with the antitumor nucleoside analog 2'-deoxy-2'-(fluoromethylene) cytidine (FMdC) on ultraviolet and X-ray sensitivity were examined. A 1-h pretreatment with FMdC increased cellular sensitivity to both X-rays and ultraviolet irradiation as determined by survival curve analysis. Increased sensitivity to killing was accompanied by a clear reduction in the rate and extent of X-ray-induced DNA strand break repair and in the closure of excision repair-dependent DNA breaks following ultraviolet irradiation. These studies demonstrate that FMdC treatment compromises the repair of both ionizing ("short-patch") and nonionizing ("long-patch") DNA damage. The mechanism by which this is likely to occur is discussed. Based on these findings, it is likely that FMdC, in addition to possessing inherent antitumor activity, might provide additional antineoplastic benefit when administered in combination therapies with radiation.
研究了用抗肿瘤核苷类似物2'-脱氧-2'-(氟亚甲基)胞苷（FMdC）处理HeLa细胞对紫外线和X射线敏感性的影响。通过存活曲线分析确定，用FMdC预处理1小时可增加细胞对X射线和紫外线照射的敏感性。对杀伤的敏感性增加伴随着X射线诱导的DNA链断裂修复的速率和程度以及紫外线照射后切除修复依赖性DNA断裂的闭合明显降低。这些研究表明，FMdC处理会损害电离（“短补丁”）和非电离（“长补丁”）DNA损伤的修复。讨论了这种情况可能发生的机制。基于这些发现，FMdC除了具有固有的抗肿瘤活性外，在与放疗联合治疗时可能还会提供额外的抗肿瘤益处。
