RESPONSE OF MAMMALIAN CELLS TO HALOGENATED PYRIMIDINES

当某些卤代嘧啶如溴脱氧尿苷（BUdR）和 碘脱氧尿苷（IUdR）掺入细胞DNA，细胞 对电离辐射更加敏感。 这一观察导致了 多年来和最近在NCI进行的几项临床研究， BUdR/IUdR是否能实现肿瘤的选择性增敏 注射后进行放疗。 一个重要的问题出现在这些 研究药物是否真的被纳入 细胞 本研究报告建议获得有关这一问题的资料 通过使用：a）输注前和输注后骨的细胞存活测定 B）使用BUdR/IUdR单克隆抗体和HPLC 实际定量肿瘤中BUdR/IUdR的量的测定， 正常组织;和c）评估可能的增强 通过IUdR掺入的化疗药物。 进一步的研究质疑 卤代嘧啶低剂量率辐照的作用。 此外，已启动试点研究，以确定卤化 嘌呤被掺入并提供X射线敏化。

When certain halogeneated pyrimidines such as Bromodeoxyuridine (BUdR) and Iododeoxyuridine (IUdR) are incorporated into cellular DNA, the cells become more sensitive to ionizing radiation. This observation has led 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 incorporated 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) use of a BUdR/IUdR monoclonal antibody and HPLC assays to actually quantitate the amount of BUdR/IUdR in tumor compared to normal tissue; and c) evaluation of the possible potentiation of chemotherapy drugs by IUdR incorporation. Further studies have questioned the role of low dose rate irradiation with halogenated pyrimidines. Additionally, pilot studies have been initiated to determine if halogenated purines are incorporated and provide x-ray sensitization.