CHEMOPREVENTION OF MNU INDUCED MAMMARY TUMORS

应使用雄性C57 BL/6 x DBA/2 F1（BDF）小鼠。 标准半纯化 饮食，如J. Nutr. 107：1340（1977）和J. Nutr. 110：1726（1980）中所述。 致癌物应为N-丁基-N-（4- 羟丁基）亚硝胺（OH-BBN）溶解在20%乙醇水溶液中， 浓度为75 mb/ml。 致癌物应每周8次给药 从动物8岁时开始，每次胃内给药7.5 mg（0.1 ml） 周的年龄。 溶剂处理动物应接受20%乙醇水溶液 溶剂，每周0.1 ml，持续8周。 化学预防剂应 由要约人采购并确定其纯度。 开始前 化学预防研究是一项为期约6周剂量选择研究， 将被执行。 选择的最高剂量（剂量MTD）应为 当与以下相比时，其不影响体重增加或产生毒性： 车辆控制。 应建立质量程序， 化学预防剂的浓度和稳定性的保证， 节食 化学预防剂应在手术前1周给予。 施用第一次致癌物剂量并进行到第二次给药结束时。 实验 膀胱应在原位固定， 显微镜下观察三个不同水平的肿瘤。 所有肿瘤 发育异常病变应根据数量和严重程度进行评分。

Male C57BL/6 x DBA/2 F1 (BDF) mice shall be used. A standard semipurified diet such as that described in J. Nutr. 107:1340 (1977) and J. Nutr. 110:1726 (1980) shall be used. The carcinogen shall be N-butyl-N-(4- hydroxybutyl) nitrosamine (OH-BBN) dissolved in 20% aqueous ethanol to a concentration of 75 mb/ml. The carcinogen shall be administered in 8 weekly intragastric doses of 7.5 mg each (0.1 ml) beginning when the animals are 8 weeks of age. Solvent-treated animals shall receive the 20% aqueous ethanol solvent, 0.1 ml per week for eight weeks. The chemopreventive agent shall be procured by the offeror and its purity established. Prior to beginning the chemopreventive study, an approximately 6 week dose selection study shall be performed. The highest dose selected (Dose MTD) shall be that which does not affect body weight gain or produce toxicity when compared to vehicle controls. A procedure shall be established for the quality assurance of the concentration and stability of the chemopreventive agent in the diet. The chemopreventive agent shall be give 1 week prior to administration of the first carcinogen dose and carried to the end of the experiment. Urinary bladders shall be fixed in situ and both grossly and microscopically observed for tumors at three different levels. All tumors and dysplastic lesions shall be scored relative to number and severity.