The effect of post-irradiation tumor oxygenation status on recovery from radiation-induced damage in vivo: with reference to that in quiescent cell populations.
OBJECTIVE
To elucidate the effect of tumor oxygenation status on recovery from damage following gamma-ray or accelerated carbon ion irradiation in vivo, including in quiescent (Q) cells.


METHODS
SCC VII tumor-bearing mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating (P) cells. They received gamma-ray or accelerated carbon ion irradiation with or without tumor clamping for inducing hypoxia. Immediately after irradiation, cells from some tumors were isolated, or acute hypoxia-releasing nicotinamide was loaded to the tumor-bearing mice. For 9 h after irradiation, some tumors were kept aerobic or hypoxic. Then isolated tumor cells were incubated with a cytokinesis blocker. The response of Q cells was assessed in terms of the micronucleus frequency using immunofluorescence staining for BrdU. That of the total (=P + Q) tumor cells was determined from BrdU non-treated tumors.


RESULTS
Clearer recovery in Q cells than total cells and after aerobic than hypoxic gamma-ray irradiation was efficiently suppressed with carbon ion beams. Inhibition of recovery through keeping irradiated tumors hypoxic after irradiation and promotion of recovery by nicotinamide loading were observed more clearly with gamma-rays, after aerobic irradiation and in total cells than with carbon ion beams, after hypoxic irradiation and in Q cells, respectively.


CONCLUSIONS
Tumor oxygenation status following irradiation can manipulate recovery from radiation-induced damage, especially after aerobic gamma-ray irradiation in total cells. Carbon ion beams are promising because of their efficient suppression of the recovery.
Masunaga
Shin-ichiro
S
Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, 2-1010, Asashiro-nishi, Kumatori-cho, Sennan-gun, Osaka 590-0494, Japan. smasuna@rri.kyoto-u.ac.jp
Hirayama
Ryoichi
R
Uzawa
Akiko
A
Kashino
Genro
G
Suzuki
Minoru
M
Kinashi
Yuko
Y
Liu
Yong
Y
Koike
Sachiko
S
Ando
Koichi
K
Ono
Koji
K
D000818:Animals; D001973:Bromodeoxyuridine / Q000008:administration & dosage / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000532:radiotherapy; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002470:Cell Survival; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005455:Fluorescent Antibody Technique; D005720:Gamma Rays; D051379:Mice; D008809:Mice, Inbred C3H; D048629:Micronuclei, Chromosome-Defective; D009369:Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D011832:Radiation Injuries; D011836:Radiation Tolerance
D001973:Bromodeoxyuridine