HYPERTHERMIA AND INCORPORATION OF HALOGENATED PYRIMIDINES - RADIOSENSITIZATION IN CULTURED RODENT AND HUMAN TUMOR-CELLS

Purpose: To investigate the possible benefit of hyperthermia (EFF) in combination with radiosensitization by halogenated pyrimidines (HPs) i n rodent as well as in human tumor cells. Methods and Materials: Expon entially growing rodent cells, radiosensitive R-1 and MOS cells and ra dioresistant RUC-II and V79 cells, and human SW1573 cells, were expose d to 0, 1, 2, and 4 mu M of chloro-(CldUrd), bromo-(BrdUrd), or iodo-d eoxyuridine (IdUrd) in the culture medium. Survival after irradiation with gamma-rays from a Cs-137 source and/or hyperthermic treatment (HT , 60 min at 42 degrees C) was determined by clonogenic assay. Linear-q uadratic analyses of the radiation survival curves were performed to a ssess sensitization in the dose range 1 to 3 Gy relevant to radiothera py. Results: The incorporation of HPs sensitized all cell lines to HT and resulted in radiosensitization dependent on the percentage of thym idine replacement. At equal levels of thymidine replacement, IdUrd was the most potent radiosensitizer. HT further increased radiation-induc ed lethality of cells that had incorporated HPs. Linear-quadratic anal yses showed that HT further increased the linear parameter of the LQ f ormula while the quadratic parameter was not significantly changed. Co nclusion: The combination of HT and HPs act additively in increasing t he radiosensitivity of rodent tumor cell lines with varying radiosensi tivities as well as of a human tumor cell line. In particular, the rat io of the linear parameter to the quadratic parameter, relevant for fr actionation effects in radiotherapy, was increased. (C) 1997 Elsevier Science Inc.