title: Responses of total and quiescent cell populations in solid tumors to carbon ion beam irradiation (290 MeV/u) in vivo.
abstract: 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.
authors.affiliation: Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, Sennan, Osaka, Japan. smasuna@rri.kyoto-u.ac.jp
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Masunaga
authors.forename: Koichi
authors.initials: K
authors.lastname: Ando
authors.forename: Akiko
authors.initials: A
authors.lastname: Uzawa
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Hirayama
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Furusawa
authors.forename: Sachiko
authors.initials: S
authors.lastname: Koike
authors.forename: Koji
authors.initials: K
authors.lastname: Ono
mesh_terms: 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
chemical_list: D002244:Carbon; D001973:Bromodeoxyuridine