Impact of the p53 status of the tumor cells on the effect of reactor neutron beam irradiation, with emphasis on the response of intratumor quiescent cells

Jpn J Cancer Res. 2002 Dec;93(12):1366-77. doi: 10.1111/j.1349-7006.2002.tb01246.x.

Abstract

Human head and neck squamous cell carcinoma cells transfected with mutant p53 (SAS/mp53) or with neo vector as a control (SAS/neo) were inoculated subcutaneously into both the hind legs of Balb/cA nude mice. Tumor-bearing mice received 5-bromo-2'-deoxyuridine (BrdU) continuously to label all proliferating (P) cells in the tumors. After administration of sodium borocaptate-10B (BSH) or p-boronophenylalanine-10B (BPA), the tumors were irradiated with neutron beams. The tumors not treated with 10B-compound were irradiated with neutron beams or gamma-rays. The tumors were then excised, minced and trypsinized. The tumor cell suspensions thus obtained were incubated with a cytokinesis blocker, and the micronucleus (MN) frequency in cells without BrdU labeling (=quiescent (Q) cells) was determined using immunofluorescence staining for BrdU. Meanwhile, 6 h after irradiation, tumor cell suspensions obtained in the same manner were used for determining the frequency of apoptosis in Q cells. The MN and apoptosis frequencies in total (P+Q) tumor cells were determined from the tumors that were not pretreated with BrdU. Without 10B-carriers, in both tumors, the relative biological effectiveness of neutrons was greater in Q cells than in total cells, and larger for low than high cadmium ratio neutrons. With 10B-carriers, the sensitivity was increased for each cell population, especially for total cells. BPA increased both frequencies for total cells more than BSH. Nevertheless, the sensitivity of Q cells treated with BPA was lower than that of BSH-treated Q cells. These sensitization patterns in combination with 10B-carriers were clearer in SAS/neo than in SAS/mp53 tumors. The p53 status of the tumor cells had the potential to affect the response to reactor neutron beam irradiation following 10B-carrier administration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / radiation effects
  • Borohydrides / therapeutic use*
  • Boron Compounds / therapeutic use*
  • Boron Neutron Capture Therapy*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / radiotherapy*
  • Cell Survival / radiation effects
  • Female
  • Genes, p53 / physiology*
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / radiotherapy*
  • Humans
  • Mice
  • Micronucleus Tests
  • Phenylalanine / analogs & derivatives*
  • Phenylalanine / therapeutic use*
  • Sulfhydryl Compounds / therapeutic use*
  • Tumor Cells, Cultured

Substances

  • 4-dihydroxyborylphenylalanine
  • Borohydrides
  • Boron Compounds
  • Sulfhydryl Compounds
  • mercaptoundecahydrododecaborate
  • Phenylalanine