IN-VIVO RADIOSENSITIZATION EFFICACY OF KU-2285 AND ETANIDAZOLE AT CLINICALLY RELEVANT LOW RADIATION-DOSES

Purpose: The in vivo radiosensitization efficacy of KU-2285 at clinica lly relevant low radiation doses (2-4 Gy) was compared with that of et anidazole using four types of assays with EMT6, SCCVII, and (CH)-H-3 m ammary tumors. Methods and Materials: The in vivo-in vitro cytokinesis -block micronucleus assay and the chromosomal aberration assay were us ed to assess the sensitizing effect at single doses of 2-4 Gy. After i n vivo treatment for tumors, tumor cells were cultured in the presence of cytochalasin B for the former assay or demecolcine for the latter assay, and the micronucleus frequency in binucleate cells and the chro mosomal frequency in metaphase cells were evaluated after 42 hr and 3 hr of culture. In addition, an in vivo-in vitro colony assay and a gro wth delay assay were performed using fractionated irradiation regimens (4 Gy X 5). Results: The sensitizer enhancement ratio for 100-400 mg/ kg of KU-2285 was between 1.12 and 1.42. KU-2285 was a more efficient sensitizer than etanidazole in 3 of 9 experiments and as efficient as etanidazole in the remaining six experiments. Conclusion: Both the mic ronucleus assay and the chromosomal aberration assay appeared to be ve ry useful in evaluating the in vivo sensitizing effect at low radiatio n doses. KU-2285 had a definite radiosensitizing effect even at low ra diation doses, and clinical trials of KU-2285 may be warranted.