QUIESCENCE IN R3327-G RAT PROSTATE TUMORS AFTER ANDROGEN ABLATION

Androgen ablation is frequently used in conjunction with radiotherapy in the treatment of high-risk prostate cancer. Androgen ablation-induc ed cell kinetic changes could result in sub-additive (increased quiesc ence) or supra-additive (reduction in repopulation) interactions with radiotherapy. The cell kinetic changes were studied in R3327-G Dunning rat prostate tumors grown iii vivo using double thymidine analogue la beling and flow cytometry, the terminal deoxynucleotidyl transferase-m ediated nick end labeling assay for apoptosis, and measurements of tum or cell numbers. Tumors grown in intact and castrate male rats were co ntinuously labeled for various periods of time with chlorodeoxyuridine and pulse-labeled with iododeoxyuridine 8 h before tumor removal. And rogen ablation resulted in a maximal reduction in labeling index (10 t o 1.6%) and an increase in potential doubling time (Tpot; 6-42 days) w ithin 3 days, which was related to a reduction in growth fraction (65% to <10%). In contrast, the length of S-phase was minimally altered (1 9 to 23 h). The response to androgen ablation involved little apoptosi s and no necrosis, and Tpot was approximately the same as the tumor vo lume doubling time. Hence, the increase in Tpot was mainly the result of a shift to quiescence, and this shift occurred with minimal cell lo ss. Because quiescence is usually associated with radioresistance, the se cell kinetic changes suggest that a subadditive interaction may occ ur for some prostate cancers when androgen ablation and irradiation ar e given together.