title: Inhibition of repair of radiation-induced damage by mild temperature hyperthermia, referring to the effect on quiescent cell populations.
abstract: 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.
authors.affiliation: Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, 2-1010 Asashiro-Nishi, Sennan-Gun, Osaka, Japan. smasuna@rri.kyoto-u.ac.jp
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Masunaga
authors.forename: Kenji
authors.initials: K
authors.lastname: Nagata
authors.forename: Minoru
authors.initials: M
authors.lastname: Suzuki
authors.forename: Genro
authors.initials: G
authors.lastname: Kashino
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kinashi
authors.forename: Koji
authors.initials: K
authors.lastname: Ono
mesh_terms: 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
chemical_list: D000730:Androstadienes; D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D002110:Caffeine; D001973:Bromodeoxyuridine; D000077191:Wortmannin