title: Evaluation of the radiosensitivity of the oxygenated tumor cell fractions in quiescent cell populations within solid tumors.
abstract: Labeling of all proliferating cells in C57BL/6J mice bearing EL4 tumors was achieved by continuous administration of 5-bromo-2'-deoxyuridine (BrdU). Tumors were irradiated with γ rays at a high dose rate or a reduced dose rate at 1 h after the administration of pimonidazole. Assessment of the responses of quiescent and total ( =  proliferating + quiescent) cell populations were based on the frequencies of micronucleation and apoptosis using immunofluorescence staining for BrdU. The response of the pimonidazole-unlabeled tumor cell fractions was assessed by means of apoptosis frequency using immunofluorescence staining for pimonidazole. The total cell fraction that was not labeled with pimonidazole showed significantly enhanced radiosensitivity. However, a significantly greater decrease in radiosensitivity, evaluated using a delayed assay or a decrease in radiation dose rate, was observed in the quiescent cell compared with the total cell population. Overall, the quiescent cell population showed significantly greater radioresistance and capacity to recover from radiation-induced damage than the total tumor cell population. Thus we believe that the subfraction of the quiescent tumor cell population that was not labeled with pimonidazole and that was probably oxygenated is a critical target in the control of solid tumors.
authors: Particle Radiation Oncology Research Center, Kyoto University, 2-1010 Asashiro-nishi, Kumatori-cho, Sennan-gun, Osaka 590-0494, Japan. smasuna@rri.kyoto-u.ac.jp
authors: Shin-ichiro
authors: S
authors: Masunaga
authors: Hideko
authors: H
authors: Nagasawa
authors: Yong
authors: Y
authors: Liu
authors: Yoshinori
authors: Y
authors: Sakurai
authors: Hiroki
authors: H
authors: Tanaka
authors: Genro
authors: G
authors: Kashino
authors: Minoru
authors: M
authors: Suzuki
authors: Yuko
authors: Y
authors: Kinashi
authors: Koji
authors: K
authors: Ono
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005720:Gamma Rays; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015162:Micronucleus Tests; D009593:Nitroimidazoles / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D011836:Radiation Tolerance
chemical_list: D009593:Nitroimidazoles; C033815:pimonidazole; D010100:Oxygen