title: Radiosensitivity of pimonidazole-unlabelled intratumour quiescent cell population to γ-rays, accelerated carbon ion beams and boron neutron capture reaction.
abstract: OBJECTIVE
  To detect the radiosensitivity of intratumour quiescent (Q) cells unlabelled with pimonidazole to accelerated carbon ion beams and the boron neutron capture reaction (BNCR).
  
  
  METHODS
  EL4 tumour-bearing C57BL/J mice received 5-bromo-2'-deoxyuridine (BrdU) continuously to label all intratumour proliferating (P) cells. After the administration of pimonidazole, tumours were irradiated with γ-rays, accelerated carbon ion beams or reactor neutron beams with the prior administration of a (10)B-carrier. Responses of intratumour Q and total (P+Q) cell populations were assessed based on frequencies of micronucleation and apoptosis using immunofluorescence staining for BrdU. The response of pimonidazole-unlabelled tumour cells was assessed by means of apoptosis frequency using immunofluorescence staining for pimonidazole.
  
  
  RESULTS
  Following γ-ray irradiation, the pimonidazole-unlabelled tumour cell fraction showed significantly enhanced radiosensitivity compared with the whole tumour cell fraction, more remarkably in the Q than total cell populations. However, a significantly greater decrease in radiosensitivity in the pimonidazole-unlabelled cell fraction, evaluated using a delayed assay or a decrease in radiation dose rate, was more clearly observed among the Q than total cells. These changes in radiosensitivity were suppressed following carbon ion beam and neutron beam-only irradiaton. In the BNCR, the use of a (10)B-carrier, especially L-para-boronophenylalanine-(10)B, enhanced the sensitivity of the pimonidazole-unlabelled cells more clearly in the Q than total cells.
  
  
  CONCLUSIONS
  The radiosensitivity of the pimonidazole-unlabelled cell fraction depends on the quality of radiation delivered and characteristics of the (10)B-carrier used in the BNCR.
  
  
  CONCLUSIONS
  The pimonidazole-unlabelled subfraction of Q tumour cells may be a critical target in tumour control.
authors.affiliation: Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, Osaka, Japan. smasuna@rri.kyoto-u.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Masunaga
authors.forename: Y
authors.initials: Y
authors.lastname: Sakurai
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: R
authors.initials: R
authors.lastname: Hirayama
authors.forename: Y
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: A
authors.initials: A
authors.lastname: Uzawa
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.forename: N
authors.initials: N
authors.lastname: Kondo
authors.forename: M
authors.initials: M
authors.lastname: Narabayashi
authors.forename: A
authors.initials: A
authors.lastname: Maruhashi
authors.forename: K
authors.initials: K
authors.lastname: Ono
mesh_terms: D000818:Animals; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D002244:Carbon; D045744:Cell Line, Tumor; D005720:Gamma Rays / Q000627:therapeutic use; D063193:Heavy Ion Radiotherapy; D008223:Lymphoma / Q000532:radiotherapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009593:Nitroimidazoles; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D011882:Radiotherapy, High-Energy / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; C033815:pimonidazole; D002244:Carbon