@article{oai:repo.qst.go.jp:00047462,
 author = {増永, 慎一郎 and 鵜澤, 玲子 and 平山, 亮一 and 松本, 孔貴 and Sakurai, Yoshinori and 田中, 浩基 and Tano, Keizo and Sanada, Yu and Suzuki, Minoru and 丸橋, 晃 and 小野, 公二 and 増永 慎一郎 and 鵜澤 玲子 and 平山 亮一 and 松本 孔貴 and 田中 浩基 and 丸橋 晃 and 小野 公二},
 issue = {4},
 journal = {World Journal of Oncology},
 month = {Sep},
 note = {Background: The aim of the study was to clarify the effect of p53
status of tumor cells on radiosensitivity of solid tumors following accelerated
carbon-ion beam irradiation compared with γ-rays or reactor
neutron beams, referring to the response of intratumor quiescent
(Q) cells.
Methods: Human head and neck squamous cell carcinoma cells transfected
with mutant TP53 (SAS/mp53) or with neo vector (SAS/neo)
were injected subcutaneously into hind legs of nude mice. Tumorbearing
mice received 5-bromo-2’-deoxyuridine (BrdU) continuously
to label all intratumor proliferating (P) cells. They received γ-rays or
accelerated carbon-ion beams at a high or reduced dose-rate. Other
tumor-bearing mice received reactor thermal or epithermal neutrons
at a reduced dose-rate. Immediately or 9 hours after the high doserate
irradiation (HDRI), or immediately after the reduced dose-rate
irradiation (RDRI), 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.
Results: The difference in radiosensitivity between the total (P + Q)
and Q cells after γ-ray irradiation was markedly reduced with reactor
neutron beams or carbon-ion beams, especially with a higher linear
energy transfer (LET) value. Following γ-ray irradiation, SAS/neo
tumor cells, especially intratumor Q cells, showed a marked reduction
in sensitivity due to the recovery from radiation-induced damage,
compared with the total or Q cells within SAS/mp53 tumors that
showed little repair capacity. In both total and Q cells within both
SAS/neo and SAS/mp53 tumors, carbon-ion beam irradiation, especially
with a higher LET, showed little recovery capacity through
leaving an interval between HDRI and the assay or decreasing the
dose-rate. The recovery from radiation-induced damage after γ-ray
irradiation was a p53-dependent event, but little recovery was found
after carbon-ion beam irradiation. With RDRI, the radiosensitivity
to reactor thermal and epithermal neutron beams was slightly higher
than that to carbon-ion beams.
Conclusion: For tumor control, including intratumor Q-cell control,
accelerated carbon-ion beams, especially with a higher LET, and reactor
thermal and epithermal neutron beams were very useful for suppressing
the recovery from radiation-induced damage irrespective of
p53 status of tumor cells.},
 pages = {398--409},
 title = {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},
 volume = {6},
 year = {2015}
}