OBJECTIVES: 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. CONCLUSION: 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. ADVANCES IN KNOWLEDGE: The pimonidazole-unlabelled subfraction of Q tumour cells may be a critical target in tumour control.
OBJECTIVES: 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:EL4tumour-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. CONCLUSION: 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. ADVANCES IN KNOWLEDGE: The pimonidazole-unlabelled subfraction of Q tumour cells may be a critical target in tumour control.
Authors: S I Masunaga; K Ono; M Suzuki; Y Nishimura; Y Kinashi; M Takagaki; H Hori; H Nagasawa; Y Uto; I Tsuchiya; S Sadahiro; C Murayama Journal: Int J Radiat Oncol Biol Phys Date: 2001-07-15 Impact factor: 7.038