EFFICACY STUDIES OF CHEMOPREVENTIVE AGENTS IN ANIMAL MOD

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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.