CHEMOPREVENTION--DMBA INDUCED MAMMARY TUMORS IN THE RAT

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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.