Dietary Intervention in the Gallus Domesticus Model of Ovarian Cancer

描述（由申请人提供）： 拟议的研究将测试西兰花丰富的饮食的有效性，并检查西兰花和吲哚-3-甲醇的作用机制，使用蛋鸡作为卵巢癌的模型。除了衰老的母鸡，没有其他自发性上皮性卵巢癌的动物模型可以模仿人类疾病。我们假设，增加西兰花的消费量可能是预防卵巢癌、增强癌症治疗和显著延长寿命的无毒方法。越来越多的证据表明，雌激素可能在卵巢肿瘤进展中发挥作用。十字花科蔬菜如西兰花含有大量潜在的生物活性化合物，包括可以水解为具有已知抗癌活性的代谢物的芥子油苷，特别是萝卜硫素和吲哚-3-甲醇（I3 C）。西兰花还含有生物活性成分，包括叶酸、钾、硒、维生素A、C、E、类胡萝卜素和多酚。西兰花的个别成分已被研究为抗癌剂。I3 C已被广泛研究，其对激素致癌作用具有保护活性，这归因于其诱导改变雌激素代谢的酶的能力，以及促进致癌物的代谢和消除。本申请的第一个目标是建立用于向母鸡饲喂西兰花的参数。拟议研究的最终目标将是确定富含西兰花的饮食在预防和抑制衰老母鸡卵巢癌方面的有效性，这将为开发人类临床试验提供基础。虽然癌症生物学家通常通过检查来自植物的特定化学成分来研究营养和癌症风险，但在化学预防研究中对整个食物的检查却很少受到关注。拟议中的研究将检查单一生物活性食品成分I3 C及其来源的整个食物西兰花，以确定其预防卵巢癌的有效性。待检验的假设是：1）富含I3 C和西兰花的饮食将改变雌激素代谢，有利于减少致癌作用; 2）用富含西兰花或I3 C的饮食喂养母鸡将导致卵巢癌发病率降低。提出了两个具体目标：目标1）在2岁白色来航母鸡中评价10%冻干西兰花与500、1000和2500 mg/kg（质量/kg食物）吲哚-3-甲醇（I3 C）补充饲料。目的2）确定西兰花补充与I3 C补充的饮食是否预防鸡卵巢癌的发展。

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.