@article{oai:repo.qst.go.jp:00045834, author = {Masunaga, Shinichiro and Hirayama, Ryoichi and Uzawa, Akiko and Kashino, Genro and Takata, Takushi and Suzuki, Minoru and Kinashi, Yuko and Liu, Yong and Koike, Sachiko and Ando, Koichi and Ono, Koji and 増永 慎一郎 and 平山 亮一 and 鵜澤 玲子 and 小池 幸子 and 小野 公二}, issue = {2}, journal = {Japanese Journal of Radiology}, month = {Feb}, note = {PURPOSE: The aim of this study was to clarify the effect of manipulating intratumor hypoxia on radiosensitivity under reduced dose-rate (RDR) irradiation. MATERIALS AND METHODS: Tumor-bearing mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating (P) cells. They received gamma-rays or accelerated carbon-ion beams at high dose-rate (HDR) or RDR with or without tumor clamping to induce hypoxia. Some mice without clamping received nicotinamide, an acute hypoxia-releasing agent or misonidazole, a hypoxic cell radio-sensitizer before irradiation. The responses of quiescent (Q) and total (= P + Q) cells were assessed by the micronucleus frequency using immunofluorescence staining for BrdU. RESULTS: The clearer decrease in radiosensitivity in Q than total cells after RDR gamma-ray irradiation was suppressed with carbon-ion beams, especially with a higher linear energy transfer value. Repressing the decrease in the radiosensitivity under RDR irradiation through keeping tumors hypoxic during irradiation and enhancing the decrease in the radiosensitivity by nicotinamide were clearer with gamma-rays and in total cells than with carbon-ion beams and in Q cells, respectively. Inhibiting the decrease in the radiosensitivity by misonidazole was clearer with gamma-rays and in Q cells than with carbon-ion beams and in total cells, respectively. CONCLUSION: Manipulating hypoxia during RDR as well as HDR irradiation influences tumor radiosensitivity, especially with gamma-rays.}, pages = {132--142}, title = {Influence of manipulating hypoxia in solid tumors on the radiation dose-rate effect in vivo, with reference to that in the quiescent cell population}, volume = {28}, year = {2010} }