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Biological effects of hormonal treatment regimens on a transplantable human prostatic tumor line (PC-82)
Abstract:
The effects of hormonal manipulation on the growth of a transplantable human prostatic carcinoma line (PC-82) were studied. The histological pattern of the PC-82 tumor, which still closely resembles the original tumor material, and the tumor growth rate did not change during the subsequent mouse passages. Growth of PC-82 tumor tissue on female and castrated male mice did not occur. Castration of tumor-bearing mice resulted in a cessation of tumor growth, after which the tumor volume decreased 50 +/- 27 per cent within 6 weeks after castration. Hormone-independent regrowth of the tumor tissue was not observed after long-term withdrawal of androgens. After a period of 10 weeks following tumor growth arrest, administration of testosterone almost directly resulted in regrowth of the tumor. Hormones, testosterone and estradiol, were administered by silastic implants. Intact male nude mice were shown to have highly fluctuating levels of testosterone. Implantation with testosterone resulted in constant levels of circulating testosterone, which could be maintained for at least 10 weeks, while the mean concentration of plasma testosterone was not different from that in control male mice. The doubling time of tumors grown on testosterone-substituted intact female and intact and castrated male mice was significantly shorter than that of tumors grown on intact male mice. Histologically the tumors grown on androgen-substituted mice were similar to those grown on untreated mice; the mitotic index, however, was much higher in the testosterone treated animals. Implantation of intact male mice with estradiol suppressed plasma testosterone to a mean level of 1 ng. per ml. and prevented the growth of PC-82 tumor tissue almost completely. Treatment of tumor-bearing mice with an estradiol implant following androgen withdrawal did not result in a further decrease of the tumor volume compared to the mice without additional estradiol implantation.