Inhibition of repair of radiation-induced damage by mild temperature hyperthermia, referring to the effect on quiescent cell populations.
OBJECTIVE
We evaluated the usefulness of mild temperature hyperthermia (MTH) as an inhibitor of the repair of radiation-induced damage in terms of the responses of the total [= proliferating (P) + quiescent (Q)] and Q cell populations in solid tumors in vivo.


METHODS
SCC VII tumor-bearing mice received a continuous administration of 5-bromo-2'-deoxyuridine (BrdU) to label all P cells. They then underwent high-dose-rate (HDR) gamma-ray irradiation immediately followed by MTH or administration of caffeine or wortmannin; alternatively, they underwent reduced-dose rate gamma-ray irradiation simultaneously with MTH or administration of caffeine or wortmannin. Nine hours after the start of irradiation, the tumor cells were isolated and incubated with a cytokinesis blocker, and the micronucleus (MN) frequency in cells without BrdU labeling (= Q cells) was determined using immunofluorescence staining for BrdU. The MN frequency in the total tumor cell population was determined using tumors that were not pretreated with BrdU.


RESULTS
In both the total and Q-cell populations, especially the latter, MTH efficiently suppressed the reduction in sensitivity caused by leaving an interval between HDR irradiation and the assay and decreasing the irradiation dose rate, as well as the combination with wortmannin administration.


CONCLUSIONS
From the viewpoint of solid tumor control as a whole, including intratumor Q-cell control, MTH is useful for suppressing the repair of both potentially lethal and sublethal damage.
Masunaga
Shin-Ichiro
S
Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, 2-1010 Asashiro-Nishi, Sennan-Gun, Osaka, Japan. smasuna@rri.kyoto-u.ac.jp
Nagata
Kenji
K
Suzuki
Minoru
M
Kashino
Genro
G
Kinashi
Yuko
Y
Ono
Koji
K
D000730:Androstadienes / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001973:Bromodeoxyuridine; D002110:Caffeine / Q000494:pharmacology / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy; D049109:Cell Proliferation / Q000528:radiation effects*; D003131:Combined Modality Therapy; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects*; D006979:Hyperthermia, Induced; D007202:Indicators and Reagents; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000517:prevention & control*; D013696:Temperature; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D000077191:Wortmannin
D000730:Androstadienes; D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D002110:Caffeine; D001973:Bromodeoxyuridine; D000077191:Wortmannin