The effect of castration on tumor growth rate and cell kinetics in hormone sensitive and hormone insensitive rat prostatic adenocarcinomas.

Abstract

Cell kinetics were measured in vivo in four experimental rat prostatic adenocarcinomas grown in normal or castrated rats. The aim was to investigate the effect of castration on growth rate and cell kinetics in hormone sensitive and hormone insensitive prostatic carcinomas. We used two anaplastic, hormone insensitive, fast growing tumors (Dunning R-3327-AT1 H and E), as well as two well differentiated, hormone sensitive, slow growing tumors (R-3327-H and R-3327-PAP). DNA ploidy, S-phase transit time (Ts), the labeling index (LI) and potential doubling time (Tpot) was determined by dual parameter flow cytometry, after in-vivo labeling, using bromodeoxyuridine (BUdR) and the tumor doubling time (DT) was determined from growth curves. After castration DT in the hormone sensitive H-subline changed from 21.7 days to 82.0 days, and in the PAP-subline from 22.2 days to 33.2 days. No significant changes in Tpot were observed. In the anaplastic tumors no differences in neither DT nor Tpot were seen. The cell loss factor (CLF) was relatively low in the two anaplastic tumors (0.55-0.59) compared to the well differentiated tumors. The CLF was unaffected by castration in the poorly differentiated tumors, whereas it increased significantly (from 0.75 to 0.92, P = 0.005) after castration in the H-tumor, and showed a non-significant increase in the PAP-tumor. This implies that the decrease in tumor growth in the hormone sensitive tumors is due to an increase in cell death, not a decrease in cell proliferation. These data indicate that CLF is the dominating factor in the reduced growth following androgen ablation in an androgen sensitive tumor. This study suggests that Tpot might be an additional predictor of a tumors proliferating rate and it may provide important information of the human prostatic cancer.