The Radiation Sensitivities of R3327-H and R3327-AT Rat Prostate Adenocarcinomas

Abstract

Dunning R3327-H and R3327-AT tumors growing s.c. in the flanks of Fischer X Copenhagen rats were irradiated with 137Cs .gamma.-rays at volumes of approximately 300 mm3. The effects of various doses of radiation were estimated by measurements of subsequent tumor growth as well as by histological evaluation. The well-differentiated, hormonally-responsive R3327-H tumor was more radiosensitive than the anaplastic R3327-AT tumor. The reasons for this increased radiation sensitivity of the R3327-H tumor include a greater "apparent" radiation sensitivity of tumor cells and the absence of tumor hypoxia. The presence of hypoxic tumor stem cells was inferred from significant radiosensitization of tumor growth delay by 0.5 mg/gm. misonidazole and by a technique which utilizes radioactively-labelled misonidazole as a marker for hypoxic cells. The persistence of a mass of R3327-H tumor tissue after aggressive radiotheraphy was not indicative of tumor cells. Furthermore, the rapid increase in volume of R3327-AT cells after aggressive radiotherapy was attributed to limited proliferation of tumor cells which were destined to ultimately die. Possible implications of these findings the management of human prostatic adenocarcinoma are discussed.