EFFICACY STUDIES OF CHEMOPREVENTIVE AGENTS

本研究的目的是测试药物对5-6周龄雄性Wistar （cpb:WU）大鼠前列腺癌的抑制作用，以50 mg/kg体重/天的剂量灌胃醋酸环丙孕酮，持续18天。在最后一次醋酸环丙孕酮给药后1天，动物按100 mg/kg体重单次注射丙酸睾酮。注射睾酮60小时后，5-6周龄动物静脉注射MNU （30mg /kg体重）。在MNU注射后的第一天，每只大鼠接受，sc，两次植入40毫克的结晶睾酮在硅胶膜胶囊中，每隔6个月重复一次。从MNU治疗前一周到研究结束，动物被喂食控制饮食或含有化学预防剂的饮食。所有大鼠均称重，并测定每周平均食量。从6个月大开始，每只大鼠每周触诊前列腺肿块的外观。如果这些动物看起来奄奄一息或已经死亡，就会被当作祭品。治疗组和对照组各有3只动物被定期处死，以评估血液激素谱和前列腺组织学变化。当大鼠出现可触及的肿瘤，濒临死亡，或在实验开始后12至14个月，这些动物被宰杀并检查肉眼和显微镜下的前列腺肿瘤和其他病变。实验动物前列腺癌专家采用盲法制备组织进行病理诊断。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滞剂。

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 .