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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
Authors: Masunaga, Shin-ichiro  kyouindb  KAKEN_id
Uzawa, Akiko
Hirayama, Ryoichi
Matsumoto, Yoshitaka
Sakurai, Yoshinori  kyouindb  KAKEN_id  orcid (unconfirmed)
Tanaka, Hiroki
Tano, Keizo  kyouindb  KAKEN_id  orcid (unconfirmed)
Sanada, Yu  kyouindb  KAKEN_id  orcid (unconfirmed)
Suzuki, Minoru  kyouindb  KAKEN_id  orcid (unconfirmed)
Maruhashi, Akira
Ono, Koji
Author's alias: 増永, 慎一郎
真田, 悠生
Keywords: p53 status
Quiescent cell
Carbon-ion beams
Reactor neutron beams
Issue Date: 2015
Publisher: Elmer Press, Inc.
Journal title: World Journal of Oncology
Volume: 6
Issue: 4
Start page: 398
End page: 409
Abstract: 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. Tumor-bearing 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 dose-rate 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.
Rights: © The authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
DOI(Published Version): 10.14740/wjon941w
PubMed ID: 28983338
Appears in Collections:Journal Articles

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