title: 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.
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.
authors.affiliation: Radiation Oncology Research Laboratory, Research Reactor Institute, Kyoto University, Sennan-gun, Osaka 590-0494, Japan. smasuna@rri.kyoto-u.ac.jp
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Masunaga
authors.forename: Koji
authors.initials: K
authors.lastname: Ono
authors.forename: Akihisa
authors.initials: A
authors.lastname: Takahashi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Sakurai
authors.forename: Ken
authors.initials: K
authors.lastname: Ohnishi
authors.forename: Toru
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kinashi
authors.forename: Masao
authors.initials: M
authors.lastname: Takagaki
authors.forename: Takeo
authors.initials: T
authors.lastname: Ohnishi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D001894:Borohydrides / Q000627:therapeutic use*; D001896:Boron Compounds / Q000627:therapeutic use*; D016754:Boron Neutron Capture Therapy; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000532:radiotherapy*; D002470:Cell Survival / Q000528:radiation effects; D005260:Female; D016158:Genes, p53 / Q000502:physiology*; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D051379:Mice; D015162:Micronucleus Tests; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D013438:Sulfhydryl Compounds / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
chemical_list: C436045:4-dihydroxyborylphenylalanine; D001894:Borohydrides; D001896:Boron Compounds; D013438:Sulfhydryl Compounds; C014651:mercaptoundecahydrododecaborate; D010649:Phenylalanine