In vivo radiosensitization efficacy of KU-2285 and etanidazole at clinically relevant low radiation doses.
OBJECTIVE
The in vivo radiosensitization efficacy of KU-2285 at clinically relevant low radiation doses (2-4 Gy) was compared with that of etanidazole using four types of assays with EMT6, SCCVII, and C3H mammary tumors.


METHODS
The in vivo-in vitro cytokinesis-block micronucleus assay and the chromosomal aberration assay were used to assess the sensitizing effect at single doses of 2-4 Gy. After in 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 chromosomal 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 growth 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.


CONCLUSIONS
Both the micronucleus assay and the chromosomal aberration assay appeared to be very useful in evaluating the in vivo sensitizing effect at low radiation doses. KU-2285 had a definite radiosensitizing effect even at low radiation doses, and clinical trials of KU-2285 may be warranted.
Oya
N
N
Department of Radiology, Faculty of Medicine, Kyoto University, Japan.
Shibamoto
Y
Y
Sasai
K
K
Sugiyama
T
T
Abe
M
M
D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D002869:Chromosome Aberrations; D004307:Dose-Response Relationship, Radiation; D017341:Etanidazole / Q000627:therapeutic use* / Q000633:toxicity; D008325:Mammary Neoplasms, Experimental / Q000473:pathology / Q000532:radiotherapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D015162:Micronucleus Tests; D009593:Nitroimidazoles / Q000627:therapeutic use* / Q000633:toxicity; D011838:Radiation-Sensitizing Agents; D011879:Radiotherapy Dosage; D014407:Tumor Cells, Cultured
D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; C069296:KU 2285; D017341:Etanidazole