ESTROGEN-TREATMENT POSTPONES THE CASTRATION-INDUCED DEDIFFERENTIATIONOF DUNNING R3327-PAP PROSTATIC ADENOCARCINOMA

Male Copenhagen x Fisher F1 rats, transplanted with the androgen-sensi tive Dunning R3327 PAP rat prostatic adenocarcinoma, were castrated wh en tumor volumes were approximally 1300 mm(3). The rats were thereafte r followed with measurements of tumor volume. Castration stopped tumor growth, but some of the tumors started to regrow after 7-36 weeks. Th ese tumors relapsing from castration treatment were now considered to be androgen-insensitive. In this study, we defined relapse as the time when the tumor volume had increased to 200% of the volume at the time for castration. At this time, the rats were treated either with estra diol-17 beta (E2, 50 mu g s.c. daily) or vehicle for 8 weeks. After th is period, tumor morphology was examined. The tumors in the vehicle-tr eated group were heterogeneous, and both highly and more dedifferentia ted parts were present. The tumor growth rate was correlated to the ep ithelial cell nuclear size and its variance, and to the mitotic index. In the E2-treated group, tumor growth rate was retarded throughout th e treatment period, and dedifferentiated tumor areas were rare. Estrog en treatment resulted in a reduction of nuclear area and mitotic index , a changed nuclear shape, and an increased apoptotic index compared t o that in vehicle-treated tumors. By castration, it is possible to ind uce an alteration of the androgen-sensitive Dunning R3327 PAP tumor ph enotype to an androgen-insensitive tumor with an altered morphology. E stradiol-17 beta apparently inhibits not only the growth, but also pos tpones the castration-induced dedifferentiation of the tumor. (C) 1994 Wiley-Liss, Inc.