title: The radiosensitivity of total and quiescent cell populations in solid tumors to 290 MeV/u carbon ion beam irradiation in vivo.
abstract: OBJECTIVE
  To clarify the radiosensitivity of intratumor total and quiescent (Q) cells in vivo to accelerated carbon ion beams compared with gamma-ray irradiation.
  
  
  METHODS
  SCC VII tumor-bearing mice received a continuous administration of 5-bromo-2'-deoxyuridine (BrdU) to label all intratumor proliferating (P) cells. Then they received 290 MeV/u carbon ions or gamma-rays. Immediately or 12 hours after the irradiation, the radiosensitivity of Q cells was assessed in terms of the micronucleus frequency using immunofluorescence staining for BrdU. That of the total (=P+Q) tumor cells was determined from the BrdU non-treated tumors based on the micronucleus frequency and clonogenic cell survival.
  
  
  RESULTS
  The apparent difference in radiosensitivity between total and Q cell populations under gamma-ray irradiation was markedly reduced with carbon ion beam, especially with a higher linear energy transfer (LET) value. Clearer repair in Q cells than total cells through delayed assay under gamma-ray irradiation was efficiently inhibited with carbon ion beams, especially with a higher LET.
  
  
  CONCLUSIONS
  In terms of tumor cell-killing effect as a whole, including intratumor Q cells, carbon ion beams, especially with higher LET values, were very useful for suppressing the dependency on the heterogeneity within solid tumors as well as depositing radiation dose precisely.
authors.affiliation: Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, Kumatori-cho, Osaka, Sennan-gun, 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; D002250:Carbon Radioisotopes / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy*; D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005455:Fluorescent Antibody Technique; D005720:Gamma Rays / Q000627:therapeutic use*; D018499:Linear Energy Transfer; D051379:Mice; D008809:Mice, Inbred C3H; D011838:Radiation-Sensitizing Agents; D013194:Staining and Labeling; D013997:Time Factors; D014410:Tumor Stem Cell Assay
chemical_list: D002250:Carbon Radioisotopes; D011838:Radiation-Sensitizing Agents; D001973:Bromodeoxyuridine