RESPONSE OF MAMMALIAN CELLS TO HALOGENATED PYRIMIDINES

当某些卤化嘧啶如溴脱氧尿嘧啶（BrdUrd）

When certain halogenated pyrimidines such as bromodeoxyuridine (BrdUrd) and iododeoxyuridine (IdUrd) are incorporated into cellular DNA, cells become more sensitive to ionizing radiation and chemotherapy drugs. 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 IdUrd infusion followed by radiation. IdUrd tumor DNA replacement data has been obtained from a number of patients (head/neck, sarcoma tumors) receiving IdUrd and has thus far revealed replacement values ranging from 7.3 to 14.2%, much higher than was seen for gliomas. Ultimately, we wish to determine if a correlation exists between IdUrd replacement and treatment outcome. We have initiated a new clinical protocol involving IdUrd combined with high and low dose rate irradiation in the treatment of cervix cancer. Biopsies will be taken prior to, during and after irradiation to determine IdUrd incorporation, labelling index, and the potential doubling time of the tumor. These parameters will be compared/contrasted with the clinical response. Laboratory studies suggest that the higher the IdUrd replacement, the greater the extent of radiosensitization. We will provide data to directly test this hypothesis in humans.