Alteration of sensitivity of intratumor quiescent and total cells to gamma-rays following thermal neutron irradiation with or without B-10-compound

Purpose: Changes in the sensitivity of intratumor quiescent (Q) and total c ells to gamma-rays following thermal neutron irradiation with or without B- 10-compound were examined. Methods and Materials: 5-Bromo-2'-deoxyuridine (BrdU) was injected to SCC V II tumor-bearing mice intraperitoneally 10 times to label all the prolifera ting (P) tumor cells. As priming irradiation, thermal neutrons alone or the rmal neutrons with B-10-labeled sodium borocaptate (BSH) or dl-p-boronophen ylalanine (BPA) were administered. The tumor-bearing mice then received a s eries of gamma-ray radiation doses, 0 through 24 h after the priming irradi ation. During this period, no BrdU was administered. Immediately after the second irradiation, the tumors were excised, minced, and trypsinized, Follo wing incubation of tumor cells with cytokinesis blocker, the micronucleus ( MN) frequency in cells without BrdU labeling (= Q cells at the time of prim ing irradiation) was determined using immunofluorescence staining for BrdU, The MN frequency in the total (P + Q) tumor cells was determined from the tumors that were not pretreated with BrdU before the priming irradiation. T o determine the BrdU-labeled cell ratios in the tumors at the time of the s econd irradiation, each group also included mice that were continuously adm inistered BrdU until just before the second irradiation using mini-osmotic pumps which had been implanted subcutaneously 5 days before the priming irr adiation, Results: In total cells, during the interval between the two irradiations, the tumor sensitivity to gamma-rays relative to that immediately after prim ing irradiation decreased with the priming irradiation ranking in the follo wing order: thermal neutrons only > thermal neutrons with BSH > thermal neu trons with BPA, In contrast, in Q cells, during that time the sensitivity i ncreased in the following order: thermal neutrons only < thermal neutrons w ith BSH < thermal neutrons with BPA. The longer the interval between the tw o irradiations, the higher was the BrdU-labeled cell ratio at the second ir radiation. The labeled cell ratio at the same time point after each priming irradiation increased in the following order: thermal neutrons only < ther mal neutrons with BSH < thermal neutrons with BPA, Conclusion: These findings indicated that the use of B-10-compound, especia lly BPA, in thermal neutron irradiation causes the recruitment from the Q t o P population. (C) 2000 Elsevier Science Inc.