Mechanisms underlying reduced growth rate in C3HBA mammary adenocarcinomas recurring after single doses of x-rays or fast neutrons.

C3HBA mammary tumors were irradiated with 3000 rads of 250-kVp X-rays or 1000 rads of 8-MeV neutrons, doses of radiation matched for producing equal growth delay. At 14 days postirradiation, tumors were regrowing at a reduced rate relative to controls. Cell kinetic parameters were examined using percentage of labeled mitoses techniques, and blood vessel spacing and tumor architecture were examined histologically to determine whether the mechanisms underlying growth rate changes were the same after neutron as after photon irradiation. The tumor volume-doubling time at 14 days posttreatment is similar in both irradiated groups (TD=117 hr for neutron-irradiated tumors, 132 hr for X-irradiated tumors) and is approximately twice as long as the doubling time of 61.4 hr in control tumors in the same size range. Control and X-irradiated tumors have median cell cycle durations of 19.3 and 18.5 hr, respectively; the more slowly growing X-irradiated tumors have a reduced growth fraction and increased cell loss factor. Regrowing neutron-irradiated tumors have a median cell cycle of 27.2 hr, with calculated growth fraction and cell loss factor values intermediate between those for control and X-irradiated tumors. Scatter in the percentage of labeled mitoses data makes it difficult to determine whether the cell cycle durations are significantly different. The average distance from tumor parenchymal interphase cells to the nearest recognizable blood vessel is nearly identical in the two irradiated groups and for both groups is significantly greater than interphase to vessel distance in controls. The average distance in irradiated tumors approaches the maximal distance for O2 diffusion in mouse adenocarcinomas of a corded structure surrounding a central blood vessel. Both neutron- and X-irradiated tumors contain more necrosis and fewer viable-appearing parenchymal cells than do control tumors of the same size. The similar growth rate and growth delay in this tumor after 3000 rads of X-rays of 1000 rads of neutrons occur in the face of possibly different cell cycle durations and seem related to similar circulatory system inadequacies which limit growth and are expressed as greater average cell-to-blood-vessel distance and increased cell loss leading to necrosis, indicating oxygen or nutrient deprivation.