CHEMOPREVENTION OF MNU-INDUCED MAMMARY TUMORS IN THE RAT

通过组合对MNU诱导的大鼠乳腺肿瘤的化学预防 化学预防剂（工作说明#61）处女，雌性斯普拉格- 道利大鼠被用于测定一系列 化学预防剂的组合以预防乳腺癌。的 动物被喂食由标准实验室食物（例如， Teklad 4%啮齿动物饲料）。致癌物质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， 化学预防实验应分别在0.8 MTD和0.4 MTD下进行 组合.剂量范围确定和联合试验的剂量 应经项目官员批准。化学预防剂是 在第一次致癌剂给药前1周开始给药， 直到实验结束。9-顺式维甲酸，DHEA，他莫昔芬是 在饮食中使用。吲哚-3-甲醇和伏罗唑将被 i.g.以恒定mg/kg体重计。血液水平和 正在确定每种病原体的摄食量（如可行）。 在实验结束时，在给药后150天处死大鼠。 致癌物剂量或濒死时。 乳腺肿瘤的数量， 动物，以及具有肿瘤的动物的百分比，以及平均肿瘤潜伏期 (mean第一个肿瘤的时间）。 乳腺 将切除肿瘤并确定每个肿瘤的平均肿瘤重量 组 应对每个肿瘤进行组织学诊断。

Chemoprevention of MNU-Induced Mammary Tumors in the Rat by combinations of chemopreventive Agents (Workstatement #61) 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 l week prior to the first carcinogen dose and given to the end of the experiment. The 9-cis-retinoic acid, DHEA, tamoxifen are being administered in the diet. Indole-3-carbinol and vorozole will be administered i.g. on a constant mg/kg body weight basis. 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.