CHEMOPREVENTION OF MNU INDUCED MAMMARY TUMORS

应选用雄性C57BL/6 x DBA/2 F1(BDF)小鼠。标准的半纯净的 像《坚果》中所描述的那样的饮食。107：1340(1977)和J.Nutr. 应使用110：1726(1980)。致癌物为N-丁基-N-(4- 羟丁基)亚硝胺(OH-BBN)溶于20%乙醇水中 浓度为75mb/ml。致癌物每周给药8次 从动物8岁开始，每次7.5毫克(0.1毫升)灌胃 只有几周大。经溶剂处理的动物应接受20%的含水乙醇 溶剂，每周0.1毫升，连续8周。化学防腐剂应当 由要约人采购，并确定其纯度。在开始之前 化学预防研究，大约6周的剂量选择研究 均须履行。选择的最高剂量(剂量MTD)应为 不会影响体重增加或产生毒性的 车辆控制系统。应为质量建立程序 确保化学防护剂的浓度和稳定性 节食。化学预防药物应在服用前1周给药。 给予第一剂量致癌物质，并持续到最后 做实验。尿囊应就地固定，并在大体和 显微镜下观察三个不同水平的肿瘤。所有肿瘤 发育不良的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.