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<ol> <LI> Consumption of food-borne bioactive compounds can protect against human diseases such as cancer, inflammation, birth defects, and microbial infection. We will determine the mechanisms by which selected compounds exert their protective action. <LI>Food-borne toxins and carcinogens are present per se or are induced by processing, preparation, and other post-harvest steps. We will identify mechanisms of action and develop biomarkers of natural and induced toxicants in food for human risk assessment and disease prevention. <LI>Selected classes of bioactive compounds show potential for beneficial or adverse effects on human health. We will discover bioactive compounds that have beneficial or adverse effects on human health.<LI>Modifying foods is an increasingly important strategy to improve nutrition and safety. Therefore, we will improve food safety by developing approaches to increase beneficial or decrease adverse effects of bioactive food constituents and microbial contaminants.
NON-TECHNICAL SUMMARY: Issues related to food safety and to diet and health impact many stakeholders. Understanding the complex relationship between dietary chemicals and human health remains a paramount concern to our primary stakeholders who include consumers, agricultural producers, food processors, health professionals, and policy makers charged with maintaining a safe and nutritious food supply. Food-borne bioactive chemicals are defined in this proposal as naturally occurring and processing-induced substances that exert beneficial or undesirable effects when consumed. This proposal will continue to focus attention on the role of food-related anticarcinogens as chemopreventive agents for reducing human cancer, and also on natural beneficial compounds which improve health and reduce the incidence of other chronic diseases. This proposal also seeks to identify, understand, and eliminate, in so far as practicable, the specific toxicants in the food supply that contribute to health deficits.<P>
APPROACH: <OL type="a"> <LI> MI and GA-ARS will collaborate to determine the effects of omega-3 fatty acid consumption on immune-mediated diseases including glomerulonephritis, asthma and food allergy, as well as how it suppresses toxic responses to fungal,plant and bacterial ribotoxins. <LI>CA-B will test the important hypothesis that DIM and other cancer protective phytochemicals, including resveratrol and curcumin, function as pro-oxidants to induce programmed cell death and to decrease tumor metastasis. These scientists will characterize the anticancer mechanism of action of DIM by determining its interactions with mitochondrial F1F0-ATP synthase and functional consequences on cellular levels of O2 and reactive oxygen species (ROS) in breast cancer cells that express a mutant form of F1F0-ATP synthase that is insensitive to DIM compared to wild-type cells. The role of activation of a specific prolyl hydroxylase enzyme in the mechanism of DIM mediated degradation of the major hypoxia response regulatory protein, HIF-1a, in hypoxic breast tumor cells also will be determined. In collaboration with MI, CA-B will examine the mechanism by which DIM can augment the immune response and determine the functional significance to this effect in prevention of cancer and viral diseases. These investigators will test the hypothesis that DIM augments the immune response by inducing the liberation of ROS and resultant activation of immune responses. CA-B plans to continue with several active collaborations with colleagues in the W1122 group. Studies with OR will continue to examine the cancer modulating and possible toxic effects of Brassica indoles in the trout cancer model and in a rodent model of prenatal development. Studies with CA-ARS will explore the antimicrobial and immune enhancing effects of DIM in rodent models of infection. MI will collaborate with CA-B in relating DIM consumption to antiviral activity using mouse models of respiratory infection (reovirus, influenza) and enteric tract infection (reovirus, norovirus). These studies along with CA-B findings will be used as a basis for uncovering the molecular mode of action for enhanced immunity with the goal of eventual application to immune enhancement in human subjects. <LI> MI will collaborate with GA-ARS by providing tissue and samples from ongoing acute and short-term chronic DON exposure studies for identification of serum-based metabolomic and proteomic markers of toxicity. To enhance MI will share new data relating increased gene expression of suppressor of cytokines(SOCs) proteins to suppressed action of growth hormone. These data will facilitate accurate prediction of adverse human health effects and enable science-based risk assessment for this mycotoxin