title: Heat exposure enhances radiosensitivity by depressing DNA-PK kinase activity during double strand break repair.
abstract: OBJECTIVE
  From the role of double strand DNA dependent protein kinase (DNA-PKcs) activity of non-homologous end joining (NHEJ) repair for DNA double strand breaks (DSBs), we aim to define possible associations between thermo-sensitisation and the enzyme activities in X-ray irradiated cells.
  
  
  METHODS
  DNA-PKcs deficient mouse, Chinese hamster and human cultured cells were compared to the parental wild-type cells. The radiosensitivities, the number of DSBs and DNA-PKcs activities after heat-treatment were measured.
  
  
  RESULTS
  Both DNA-PKcs deficient cells and the wild-type cells showed increased radiosensitivities after heat-treatment. The wild-type cells have two repair processes; fast repair and slow repair. In contrast, DNA-PKcs deficient cells have only the slow repair process. The fast repair component apparently disappeared by heat-treatment in the wild-type cells. In both cell types, additional heat exposure enhanced radiosensitivities. Although DNA-PKcs activity was depressed by heat, the inactivated DNA-PKcs activity recovered during an incubation at 37 °C. DSB repair efficiency was dependent on the reactivation of DNA-PKcs activity.
  
  
  CONCLUSIONS
  It was suggested that NHEJ is the major process used to repair X-ray-induced DSBs and utilises DNA-PKcs activity, but homologous recombination repair provides additional secondary levels of DSB repair. The thermo-sensitisation in X-ray-irradiated cells depends on the inhibition of NHEJ repair through the depression of DNA-PKcs activities.
authors.affiliation: Department of Radioisotope Medicine, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University , Nagasaki , Japan .
authors.forename: Makoto
authors.initials: M
authors.lastname: Ihara
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takeshita
authors.forename: Kumio
authors.initials: K
authors.lastname: Okaichi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Okumura
authors.forename: Takeo
authors.initials: T
authors.lastname: Ohnishi
mesh_terms: D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D002478:Cells, Cultured; D003412:Cricetulus; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D051747:DNA-Activated Protein Kinase / Q000172:deficiency / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D051379:Mice; D011836:Radiation Tolerance; D014965:X-Rays
chemical_list: D051747:DNA-Activated Protein Kinase