EFFECT OF RADIOSENSITIZERS AND RADIOPROCTECTORS ON DNA DAMAGE PRODUCED BY X-RAYS

我们已经完成了卤代嘧啶放射增敏剂的研究， IUdR和BUDR。IUdR目前正在作为放射增敏剂进行临床试验。 这种试剂掺入细胞后使细胞对辐射敏感。 DNA取代胸腺嘧啶核苷。我们之前已经证明，DNA的产量 含IUdR的细胞经x射线照射后，断链增加。 目前IUdR和BUDR辐射分解的模型预测只有单链 损伤应该在DNA中产生。然而，最重要的病变是 X射线致死很可能是DNA双链断裂。我们发现， 经X射线照射的细胞DNA中IUdR的辐解导致流动反应 中间体既破坏含有IUdR的链，也破坏 在这些实验中不含IUdR的互补链。 IUdR诱导的链断裂在未被取代的 被取代的链中的链。另有较小的升幅。 在含有IUdR-DNA的细胞中，未被取代的双链DNA发生链断裂。在……里面 细胞存活实验，细胞仅经历1次IUdR加倍 显示的放射增敏作用几乎与经历2次倍增的细胞相同 其中两条都被替换了。

We have completed studies with the halogenated pyrimidine radiosensitizers, IUdR and BUdR. IUdR is currently in clinical trials as a radiosensitizer. This agent sensitizes cells to radiation after incorporation into cellular DNA in place of thymidine. We have previously shown that the yield of DNA strand breaks was increased in cells containing IUdR after x-irradiation. Current models of IUdR and BUdR radiolysis predict that only single strand damage should be produced in DNA. However, the lesion most important in x-ray lethality is probably DNA double strand breaks. We have found that radiolysis of IUdR in DNA of cells x-irradiated leads to mobile reactive intermediates which damage both the strand containing the IUdR and also the complementary strand which did not contain IUdR in these experiments. IUdR-induced strand breaks were almost as frequent in the unsubstituted strand as in the substituted strand. There was also a smaller increase in strand breaks in unsubstituted duplex DNA in cells containing IUdR-DNA. In cell survival experiments, cells undergoing only 1 doubling with IUdR showed almost as much radiosensitization as cells undergoing 2 doublings where both strands were substituted.