EFFICACY STUDIES OF CHEMOPREVENTIVE AGENTS IN ANIMAL MOD

处女雌性Sprague-Dawley大鼠被用来确定一系列化学预防剂组合预防乳腺癌的功效。这些动物被喂食由标准实验室饲料（例如Teklad 4%啮齿动物饲料）组成的饮食。致癌物n -甲基-n -亚硝基脲（MNU）在约120日龄时施用，用于诱导乳腺肿瘤。确定每种药剂组合的MTD，并在每种药剂组合的0.8 MTD和0.4 MTD下进行化学预防实验。测距试验和组合试验的剂量应由项目官员批准。化学预防剂在第一次致癌物剂量前一周开始施用，直至实验结束。9-顺式维甲酸、雷洛昔芬、塞来昔布、齐列汀可在饮食中单独或联合使用。正在确定每种制剂的血液水平和食物消耗量（如果可行）。实验结束时，在致癌物剂量后150天或濒死时处死大鼠。记录每只动物的乳腺肿瘤数量、肿瘤动物的百分比、平均肿瘤潜伏期（到第一个肿瘤的平均时间）。切除乳腺肿瘤，计算各组肿瘤的平均重量。每个肿瘤都要做组织学诊断。

Virgin, female Sprague-Dawley rats are being used to determine the efficacy of a series of combinations of chemopreventive agents to prevent mammary cancer. The animals are being fed a diet consisting of standard laboratory chow (e.g. Teklad 4% Rodent Chow). The carcinogen, N-methyl-N-nitrosourea (MNU), administered at about 120 days of age, is used to induce mammary tumors . An MTD for each combination of agents is established and the chemoprevention experiment shall proceed at 0.8 MTD and 0.4 MTD of each combination. Doses for both the rangefinding and the combination tests shall be approved by the Project Officer. The chemopreventive agents is administered starting 1 week prior to the first carcinogen dose and given to the end of the experiment. 9-cis Retinoic acid, Raloxifene, Celecoxib, Zileutin are being administered in the diet singly and in combination. Blood levels and food consumption are being determined for each agent (where practicable). The rats are sacrificed at the end of the experiment at 150 days after the carcinogen dose or when moribund. The number of mammary tumors per animal, and the percent of animals with tumors, and the mean tumor latency (mean time to first tumor) shall be recorded for each group. The mammary tumors shall be excised and a mean tumor weight established for each group. A histological diagnosis shall be made on each tumor.