EFFICACY STUDIES OF CHEMOPREVENTIVE AGENTS IN ANIMAL MOD

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The efficacy of a variety of chemopreventive agents to reduce or inhibit ovarian cancer using female Lewis rats is being studied. Female Lewis rats are being injected s.c. with 0.8 mg N-nitroso-(2-oxopropyl)amine (BOP) /kgBW at 10 and 14 days of age. After the 21 day weaning period the female (30/group) rats begin receiving CP agents either in the diet, injected or by gavage for the duration of the study. The study runs approximately 30 weeks (until the rats are ~8 months old). The doses to be administered are determined following a six week rangefinding assay. Two doses per agent are administered. The animals are weighed and palpated for ovarian masses once per week. The ovaries are removed at the end of the study (~8 months) and histologically examined for lesions. The incidence, the multiplicity, the histological classification and locations of the tumors are recorded. The test agents to be tested are: Medroxyprogesterone (injected at 20 days of age then bimonthly), an antiestrogen (TBN), Medroxyprogesterone+Antiestrogen, 9-cis-retinoic acid, 4HPR, and Apomine (SR-45023A) (Symphar, Inc). All groups are coded and groups are scored in a blinded manner by two independent scorers. An appropriate statistical analysis on all data will determine significance of enhancing or inhibiting effects of the various agents. The classes of agent being studied include retinoids, antiestrogenic, and an ovarian specific drug Apomine.