Synergism of myc with ras in the induction of radioresistance

transplantation, all animals obtained a single whole body irradiation of 5.0 Gy to suppress residual NKand macrophage-related immunity. Groups of 10 to 12 animals were stratified according to tumor size (median treatment volume: 200~1) and randomly allocated to 4 photonand 2 fast neutron single dose regimens including one control group for each treatment. The dose rates of the 6oCo source and the d(l4)+Be neutrons were 2.9 Gy/min and 0.5 Gy/min. respectively. The tumors were rendered acutely hypoxic by clamping the tumor bed 10 min prior to and during irradiation. Total doses ranged from 8 to 40 Gy for photons and 3 to 10 Gy for fast neutrons, respectively. The endpoint of the experiments was the specific growth delay (SGD). In terms of an isoeffective SGD of 2.0 DT’s, total photonand neutron doses in the range of 3.3 to 36.7 Gy and 1.3 to 8.9 Gy, respectively, were necessary. No significant correlation was found between the DT’s of the xenografts and their radiosensitivities or values of the relative biological effectiveness (RBE). The ranking of the tumors according to the growthand SGD agreed with a correlation coefficient of 0.9. At SGD’s of 1.0 and 2.0 DT’s, RBE’s ranged from 1.7 to 6.7 and 1.5 to 6.1, respectively. The RBE’s remained constant or decreased with increasing effect level. The RBE values were corrected for the oxygen enhancement ratio (OER) at a SGD level of 1 and 2 DT’s, which was determined to be about 1.6 and 1.2 with respect to photons and neutrons in the EL5-line. The corrected RBE-values at a SGD level of 1.0 (2.0) DT’s were in the range of 1.1 (1.0) to 4.5 (4.11, respectively. Thus assuming an RBE of 3.0 as to be adequate for normal soft tissues, a significant gain for at least 4 out of 10 tumor lines was observed. These results indicate a potential usefulness of fast neutrons for clinical radiation therapy of soft tissue tumors as well as the considerable heterogeneity of the radiation response despite homogeneous hypoxia.