Journal Article The Effect of p53 Status of Tumor Cells on Radiosensitivity of Irradiated Tumors With Carbon-Ion Beams Compared With γ-Rays or Reactor Neutron Beams

増永, 慎一郎  ,  鵜澤, 玲子  ,  平山, 亮一  ,  松本, 孔貴  ,  Sakurai, Yoshinori  ,  田中, 浩基  ,  Tano, Keizo  ,  Sanada, Yu  ,  Suzuki, Minoru  ,  丸橋, 晃  ,  小野, 公二

6 ( 4 )  , pp.398 - 409 , 2015-09 , World J Oncol and Elmer Press Inc
Background: The aim of the study was to clarify the effect of p53status of tumor cells on radiosensitivity of solid tumors following acceleratedcarbon-ion beam irradiation compared with γ-rays or reactorneutron beams, referring to the response of intratumor quiescent(Q) cells.Methods: Human head and neck squamous cell carcinoma cells transfectedwith mutant TP53 (SAS/mp53) or with neo vector (SAS/neo)were injected subcutaneously into hind legs of nude mice. Tumorbearingmice received 5-bromo-2’-deoxyuridine (BrdU) continuouslyto label all intratumor proliferating (P) cells. They received γ-rays oraccelerated carbon-ion beams at a high or reduced dose-rate. Othertumor-bearing mice received reactor thermal or epithermal neutronsat a reduced dose-rate. Immediately or 9 hours after the high doserateirradiation (HDRI), or immediately after the reduced dose-rateirradiation (RDRI), the tumor cells were isolated and incubated witha cytokinesis blocker, and the micronucleus (MN) frequency in cellswithout BrdU labeling (Q cells) was determined using immunofluorescencestaining for BrdU.Results: The difference in radiosensitivity between the total (P + Q)and Q cells after γ-ray irradiation was markedly reduced with reactorneutron beams or carbon-ion beams, especially with a higher linearenergy transfer (LET) value. Following γ-ray irradiation, SAS/neotumor cells, especially intratumor Q cells, showed a marked reductionin sensitivity due to the recovery from radiation-induced damage,compared with the total or Q cells within SAS/mp53 tumors thatshowed little repair capacity. In both total and Q cells within bothSAS/neo and SAS/mp53 tumors, carbon-ion beam irradiation, especiallywith a higher LET, showed little recovery capacity throughleaving an interval between HDRI and the assay or decreasing thedose-rate. The recovery from radiation-induced damage after γ-rayirradiation was a p53-dependent event, but little recovery was foundafter carbon-ion beam irradiation. With RDRI, the radiosensitivityto reactor thermal and epithermal neutron beams was slightly higherthan that to carbon-ion beams.Conclusion: For tumor control, including intratumor Q-cell control,accelerated carbon-ion beams, especially with a higher LET, and reactorthermal and epithermal neutron beams were very useful for suppressingthe recovery from radiation-induced damage irrespective ofp53 status of tumor cells.

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