Dietary Intervention in the Gallus Domesticus Model of Ovarian Cancer

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DESCRIPTION (provided by applicant): The proposed studies will test the effectiveness of a broccoli-enriched diet, and examine the mechanism of action of broccoli and indole-3-carbinol using the laying hen as a model of ovarian carcinoma. With the exception of the aging hen, there are no other animal models of spontaneous epithelial ovarian cancer that mimic the human disease. We hypothesize that increasing the consumption of broccoli may be a nontoxic way to prevent ovarian cancer, augment cancer therapy and to significantly increase life span. There is growing evidence that estrogens may play a role in ovarian tumor progression. Cruciferous vegetables such as broccoli contain a vast array of potentially bioactive compounds, including glucosinolates that can be hydrolyzed to metabolites with known anticarcinogenic activity, particularly sulforaphane and indole-3-carbinol (I3C). Broccoli also contains bioactive components including folate, potassium, selenium, vitamins A, C, E, carotenoids, and polyphenols. Individual components of broccoli have been studied as anticancer agents. I3C has been studied extensively has protective activity against hormonal carcinogenesis attributed to its ability to induce enzymes that alter estrogen metabolism in addition to facilitating metabolism and elimination of carcinogens. The first goal of this application is to establish the parameters for feeding broccoli to hens. The ultimate goal of the proposed studies will be to determine the effectiveness of a broccoli-enriched diet in the prevention and suppression of ovarian cancer in the aging hen, which will provide the foundation for developing a clinical trial in humans. Whereas cancer biologists have typically approached nutrition and cancer risk by examining specific chemical components derived from plants, examination of whole foods in chemoprevention studies has received less attention. The proposed studies will examine a single bioactive food component, I3C, and the whole food from which it's derived, broccoli, to determine their effectiveness in the prevention of ovarian cancer. The hypotheses to be tested are that 1) I3C and broccoli enriched diets will alter estrogen metabolism in favor of reducing carcinogenesis; and 2) feeding hens a diet enriched with broccoli or I3C will result in a reduction in the incidence of ovarian cancer. Two specific aims are proposed: Aim 1) Evaluate a 10% freeze-dried broccoli vs. 500, 1000 and 2500 mg/kg (mass per kg food) indole-3-carbinol (I3C) supplemented diets in 2 year old white Leghorn hens. Aim 2) Determine if a broccoli supplemented vs. I3C supplemented diets prevent the development of ovarian cancer in chickens.