RESPONSE OF MAMMALIAN CELLS TO HALOGENATED PYRIMIDINES

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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.