Responses of total and quiescent cell populations in solid tumors to carbon ion beam irradiation (290 MeV/u) in vivo

Radiat Med. 2008 Jun;26(5):270-7. doi: 10.1007/s11604-008-0227-x. Epub 2008 Jul 27.

Abstract

Purpose: 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.

Materials and 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bromodeoxyuridine / administration & dosage
  • Carbon / therapeutic use*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / radiotherapy*
  • Cell Proliferation
  • Cell Survival
  • Female
  • Fluorescent Antibody Technique
  • Gamma Rays / therapeutic use
  • Linear Energy Transfer
  • Mice
  • Micronucleus Tests
  • Radiation Tolerance
  • Radiobiology
  • Tumor Cells, Cultured / radiation effects
  • Xenograft Model Antitumor Assays

Substances

  • Carbon
  • Bromodeoxyuridine