Retardation of tumor growth in mice caused by radiation-induced injury of tumor bed stroma: dependency on tumor type.

Dependency on tumor type of tumor growth retardation caused by the radiation-induced damage of tumor bed stroma, a phenomenon known as the tumor bed effect (TBE), was investigated using two mammary carcinomas designated MCA-4 and MCA-K and two fibrosarcomas designated FSA and NFSA, all syngeneic to C3Hf/Kam mice. Inoculations of tumor cells were given s.c. into the right hind thighs of mice either treated or not treated 1 day earlier with graded doses of gamma-rays; tumor latency and growth rate were determined. Tumor latency was prolonged and tumor growth was retarded, but the magnitude of these two features of TBE greatly depended on radiation dose and tumor type. TBE began to appear at doses of 5-10 Gy and then sharply increased as the dose of radiation was increased up to between 20 and 30 Gy, at which point a plateau was achieved. TBE was also significant after 40 and 60 Gy total dose given in daily fractions of 2 Gy 5 times per week, a schedule commonly used in radiotherapy treatment of cancer patients. Carcinomas exhibited more pronounced TBE than fibrosarcomas, with NFSA showing only minimal TBE. Radiation-inactivated MCA-4 and FSA cells admixed with viable MCA-4 cells reduced tumor latency, but not the tumor growth delay, of resulting MCA-4 tumors in preirradiated legs. In contrast, admixture of irradiated NFSA and viable MCA-4 cells abolished growth delay but did not influence tumor latency of the TBE phenomenon. Thus the type of a tumor growing in the irradiated tissue is a very important factor that determines the expression of TBE.