Responses of total and quiescent cell populations in solid tumors to carbon ion beam irradiation (290 MeV/u) in vivo.
OBJECTIVE
The aim of this study was to clarify the radiosensitivity of intratumor total cells and quiescent (Q) cells in vivo to accelerated carbon ion beams compared with gamma-ray irradiation.


METHODS
Squamous cell carcinoma (SCC) VII tumor-bearing mice received continuous administration of 5-bromo-2'-deoxyuridine (BrdU) to label all intratumor proliferating (P) cells. They then were exposed to carbon ions (290 MeV/u) or gamma-rays. Immediately after and 12 h after irradiation, immunofluorescence staining for BrdU was used to assess the response of Q cells in terms of micronucleus frequency. The response of the total (P + Q) tumor cells was determined from the tumors not treated with BrdU.


RESULTS
The apparent difference in radiosensitivity between total and Q cell populations under gamma-ray irradiation was markedly reduced with carbon ion beams, especially with a higher linear energy transfer (LET) value. Clearer recovery in Q cells than in total cells through delayed assay under gamma-ray irradiation was efficiently inhibited by carbon ion beams, especially those with a higher LET.


CONCLUSIONS
In terms of the tumor cell-killing effect as a whole, including intratumor Q cells, carbon ion beams, especially with higher LET values, were extremely useful for suppressing the dependence on the heterogeneity within solid tumors as well as depositing the radiation dose precisely.
Masunaga
Shin-Ichiro
S
Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, Sennan, Osaka, Japan. smasuna@rri.kyoto-u.ac.jp
Ando
Koichi
K
Uzawa
Akiko
A
Hirayama
Ryoichi
R
Furusawa
Yoshiya
Y
Koike
Sachiko
S
Ono
Koji
K
D000818:Animals; D001973:Bromodeoxyuridine / Q000008:administration & dosage; D002244:Carbon / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000532:radiotherapy*; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D005455:Fluorescent Antibody Technique; D005720:Gamma Rays / Q000627:therapeutic use; D018499:Linear Energy Transfer; D051379:Mice; D015162:Micronucleus Tests; D011836:Radiation Tolerance; D011853:Radiobiology; D014407:Tumor Cells, Cultured / Q000528:radiation effects; D023041:Xenograft Model Antitumor Assays
D002244:Carbon; D001973:Bromodeoxyuridine