RESPONSE OF QUIESCENT AND TOTAL TUMOR-CELLS IN SOLID TUMORS TO NEUTRONS WITH VARIOUS CADMIUM RATIOS

Purpose: Response of quiescent (Q) and total tumor cells in solid tumo rs to neutron irradiation with three different cadmium (Cd) ratios was examined. The role of Q cells in turner control was also discussed. M ethods and Materials: C3H/He mice bearing SCC VH tumors received conti nuous administration of 5-bromo-2'-deoxyuridine(BrdU) for 5 days using implanted mini-osmotic pumps to label all proliferating (P) cells. Th irty minutes after intraperitoneal injection of sodium borocaptate-B-1 0 (BSH), or 3 h after oral administration of dl-p-boronophenylalanine- B-10 (BPA), the tumors were irradiated with neutrons, or those without B-10-compounds were irradiated with gamma rays. This neutron irradiat ion was performed using neutrons with three different cadmium (Cd) rat ios. The tumors were then excised, minced, and trypsinized. The tumor cell suspensions were incubated with cytochalasin-B (a cytokinesis-blo cker), and the micronucleus (MN) frequency in cells without BrdU label ing (Q cells) was determined using immunofluorescence staining for Brd U, The MN frequency in total (P + Q) tumor cells was determined from t umors that were not pretreated with BrdU, The sensitivity to neutrons was evaluated in terms of the frequency of induced micronuclei in binu clear tumor cells (MN frequency). Results: Without B-10-compounds, the MN frequency in Q cells was lower than that in the total cell populat ion. The sensitivity difference between total and Q cells was reduced by neutron irradiation. Relative biological effectiveness (RBE) of neu trons compared with gamma rays was larger in Q cells than in total cel ls, and the RBE values for low-Cd-ratio neutrons tended to be larger t han those for high-Cd-ratio neutrons. With B-10-compounds, MN frequenc y for each cell population was increased, especially for total cells. This increase in MN frequency was marked when high-Cd-ratio neutrons w ere used. BPA increased the MN frequency for total tumor cells more th an BSH, Nevertheless, the sensitivity of Q cells treated with BPA was lower than that in BSH-treated Q cells. This tendency was clearly obse rved in high-Cd-ratio neutrons. Conclusion: From the viewpoint of enha ncing the Q-cell sensitivity, tumors should be irradiated with high-Cd -ratio neutrons after BSH administration. However, normal tissue react ion remains to be examined because of its low tumor-to-normal tissue a nd tumor-to-blood biodistribution ratios. (C) 1998 Elsevier Science In c.