Influence of manipulating hypoxia in solid tumors on the radiation dose-rate effect in vivo, with reference to that in the quiescent cell population

Authors:   Shin Masunaga,Ryoichi Hirayama,Akiko Uzawa,Genro Kashino,Takushi Takata,Hiroki Tanaka,Minoru Suzuki,Yuko Kinashi,Yong Liu,Sachiko Koike,Koichi Ando,Koji Ono
Journal: Japanese Journal of Radiology
https://doi.org/10.1007/s11604-009-0397-1
Abstract: 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. {textcopyright} 2010 Japan Radiological Society.