EFFICACY STUDIES OF CHEMOPREVENTIVE AGENTS

本研究的目的是测试药剂抑制前列腺癌的功效。5-6周龄的雄性Wistar（cpb：WU）大鼠通过管饲法以50 mg/kg体重每天用乙酸环丙孕酮预处理18天。在最后一次醋酸环丙孕酮给药后一天，动物接受单次s.c.注射100 mg/kg体重的丙酸睾酮。注射睾酮后60小时，在5-6周龄时用MNU（30 mg/kg体重）静脉内接种动物。 在MNU注射后的第二天，每只大鼠皮下接受，在硅橡胶膜的胶囊中植入两次40 mg结晶睾酮，每隔6个月重复一次。从MNU处理前一周至研究结束，对动物饲喂对照饲料或含有化学预防剂的饲料。每周对所有大鼠称重并测定平均摄食量。从6月龄开始，每周触诊每只大鼠的前列腺肿块。 如果动物出现濒死状态，则将其处死并进行尸检。定期处死处理组和对照组各3只动物，以评估血液激素分布和前列腺组织学变化。当大鼠出现可触知的肿瘤、濒死或在实验开始后12至14个月时，将这些动物解剖并检查大体和显微镜下的前列腺肿瘤和所述的其它病变。以盲法制备组织，由实验动物前列腺癌专家进行病理诊断。正在研究的药物包括：大豆蛋白提取物、BBI、脂氧合酶抑制剂和雄激素阻断剂。

The objective of this study is to test agents for efficacy to inhibit prostate cancer male Wistar (cpb:WU) rats 5-6 weeks of age are being pretreated with cyproterone acetate by gavage at 50 mg/kg body weight daily for 18 days. One day after the last cyproterone acetate dose animals receive a single s.c. injection of testosterone propionate at 100 mg/kg body weight. Sixty hours after the testosterone injection the animals are being inoculated i.v. with MNU (30 mg/kg body weight) at 5-6 weeks of age. On the day after MNU injection each rat receives, s.c., two implants of 40 mg of crystalline testosterone in a capsule of silastic membrane, which is repeated at intervals of 6 months. Animals are being fed either control diets or diets containing the chemopreventive agent from one week prior to MNU treatment to the end of the study. All rats are weighed and average food consumption determined weekly. Each rat is palpated weekly for the appearance of prostatic masses, beginning at 6 months of age. The animals are sacrificed if they appear moribund and necropsied. Three animals from each of the treatment and the control groups are being sacrificed periodically for assessing blood hormone profiles and histological changes in the prostate. When rats develop a palpable tumor, are moribund, or at 12 to 14 months after initiation of the experiment, These animals are sacrified and examined for gross and microscopic prostate tumors and other lesions as described. The tissues are prepared a blinded manner for pathological diagnosis by an experimental animal prostate cancer expert. The agents being studied include: Soy Protein Extract, BBI, a lipoxygenase inhibitor, and an androgen blocker .