RESPONSE OF MAMMALIAN CELLS TO HALOGENATED PYRIMIDINES

当某些卤代嘧啶类化合物，如溴脱氧尿苷(BUDR)和 碘脱氧尿苷(IUdR)被掺入细胞DNA，细胞 对电离辐射更加敏感。这一观察导致了 多年来的几项临床研究，最近在NCI进行了评估 BUDR/IUdR能否实现肿瘤的选择性增敏 输液后进行放射治疗。在这些问题中出现了一个重要问题 关于药物是否确实被掺入的研究 细胞。这项研究建议获取关于这个问题的信息 应用：a)输注前后骨细胞存活率的测定 骨髓前体细胞；b)姐妹染色单体染色是否可以 在骨髓干细胞中观察到；以及c)BUDR/IUdR单抗的使用 抗体和高效液相色谱定量测定BUDR/IUdR 肿瘤与正常组织相比。进一步的研究对这一角色提出了质疑 卤代嘧啶的低剂量率照射。另外， 已经启动了试点研究，以确定卤化嘌呤是否 并提供X射线敏化。

When certain halogenated pyrimidines such as Bromodeoxyuridine (BUdR) and Iododeoxyuridine (IUdR) are incorporated into cellular DNA, the cells become more sensitive to ionizing radiation. This observation has lead to several clinical studies over the years and recently at the NCI to evaluate whether selective sensitization of tumors could be achieved by BUdR/IUdR infusion followed by radiation. An important question arises in these studies regarding whether or not the drug actually is incoporated into cells. This study proposes to obtain information regarding this question by using: a) cell survival determinations of pre and post infusion bone marrow precursor cells; b) whether or not sister chromatid staining can be observed in bone marrow stem cells; and c) use of BUdR/IUdR monoclonal antibody and HPLC assays to actually quantitate the amount of BUdR/IUdR in tumor compared to normal tissue. Further studies have questioned the role of low dose rate irradiation with halogenated pyrimidines. Additionally, pilot studies have been initiated to determine if halogenated pruines are incorporated and provide x-ray sensitization.