Brief Summary of Minutes of Annual Meeting

Objective 1: Determine the mechanisms by which dietary bioactive compounds protect against human diseases. Dr. Abby Benninghoff and colleagues in the Applied Nutrition Research Group (Utah State University) previously developed a new rodent diet that models typical Western nutrition. Rodent cancer studies typically use defined diets with nutrient profiles optimized for rodent health. However, a defined rodent diet that represents typical American nutrition in all aspects, including calorie sources and macro- and micronutrient composition, was not available. They therefore used a nutrient density approach to formulate the new Total Western Diet (TWD) based on NHANES data for macro- and micronutrient intakes. As proof of principle, they employed the azoxymethane (AOM) model of colorectal cancer in mice fed either TWD or AIN93G basal diets supplemented with or without 0.2% green tea extract in the drinking water. Previously, they reported that green tea extract suppressed the development of preneoplastic lesions, termed aberrant crypt foci, in mice fed the TWD, but not in mice fed the optimal AIN93G diet. During the current reporting period, they have performed additional analyses to determine the impact of the experimental diets and green tea extract on the cecal metagenome and short chain fatty acids. They have determined that green tea extract was associated with increased cecum weight and negatively correlated with final body weight. Also, the relative abundance of bifidobacterium species was higher in animals provided green tea and the TWD. A metagenomics analysis of the cecal contents revealed that green tea supplementation reduced the relative abundance of genes associated with butyrate metabolism, suggesting a reduced capacity for butyrate production. Additionally cecal butyrate, acetate and total short chain fatty acids were lower in mice supplemented with green tea. These observations suggest that green tea may reduce body weight gain, without any accompanying change in energy intake, by reducing the amount of energy extracted from the diet by gut microbiota. Last year, Dr. Benninghoff and colleagues reported results of a second study with the TWD using the AOM+dextran sodium sulfate (DSS) model of inflammation?associated colorectal cancer. From that study, they determined that the effect of TWD on tumorigenesis in mice was attributed to the micronutrient fraction of the diet. In 2014, we performed a third pre?clinical study to investigate the impact of TWD in a genetic model of colorectal cancer using the APCmin/+ mouse model. APCmin/+ mice spontaneously develop tumors of the small intestine, and with the addition of 1% DSS via drinking water, they also develop colon tumors. This experiment employed a 2x3 design, where mice received either 1%DSS or plain water and either the optimal AIN93G diet, the TWD or the 45% fat DIO diet. None of the experimental diets, nor addition of DSS, significantly affected the incidence of small intestine (SI) tumors, although a significant main effect of the DIO diet was evident for SI tumor multiplicity and tumor burden. TWD did not markedly enhance carcinogenesis of the small intestine. Alternatively, the TWD had a profound effect on tumorigenesis in the colon, notably in animals provided 1%DSS to promote colonic inflammation. Exposure to the TWD significantly increased colon tumor incidence and caused a 5?fold increase in colon tumor multiplicity, whereas the DIO diet was without any effect on colon tumorigenesis. Dr. Roger Coulombe and colleagues (Utah State University) reported on a project in which they are using probiotics as chemopreventive agents. Probiotic bacteria such as Lactobacillus (the type used in fermented foods such as yogurt) have been shown in laboratory and limited clinical studies, to prevent the absorption and reduce exposure to dietary carcinogens, such as AFB1. The presumed mechanism of action is via non?specific binding of AFB1 by cell wall glycoproteins, which reduces intestinal absorption and hence bioavailability of this mycotoxin. They have previously reported that the probiotic Lactobacillus (a mixture of Lactobacillus rhamnosus strain GG and LC-­705, Propionibacterium freundenreichii sp shermani and Bifidobacterium sp (LGG)) protected against markers of aflatoxicosis in turkeys, one of the most sensitive animals known to AFB toxicity. This year, they used RNA? sequencing (RNA?seq) to investigate the impact of probiotics on the expression pattern of splenic RNA transcripts in turkeys challenged with dietary AFB1. Ten?day old male Nicholas strain domestic turkeys were randomized into one of four groups: LGG only, LGG+AFB1, PBS control, and AFB1 only. Birds were pretreated with probiotic (5 X 10 CFU/0.5 ml PBS) or PBS by oral gavage for the first 10 days, before starting a 10?day dietary AFB1 treatment (1 ppm). RNA?seq libraries were generated from 3 spleen samples per treatment group (n = 12) and were sequenced on the Illumina GA IIx. Over 105 M single?end reads were produced and de novo assembled into approximately 270,000 predicted transcript fragments. 982 transcripts had significant differential expression in at least one pair?wise comparison between treatment groups. AFB1 exposure down-regulated transcripts from antimicrobial genes such as angiogenin and lysozyme G; however, other immune-related transcripts, including granzyme A, lymphotactin, and perforin 1, were up-regulated. Increased expression of these interleukin-2 response genes could be indicative of lymphocyte activation or apoptosis. Probiotic + AFB1 mitigated some expression changes induced by AFB1, but probiotics alone had a suppressive effect on immune transcripts and may affect the cytotoxic potential of turkey splenocytes. Pathways and genes identified by transcriptome analysis in the spleen provide targets to elucidate the molecular basis of AFB1 immunotoxicity and to determine the mechanism of probiotic chemoprevention at the RNA level. One possible interpretation of these results is that probiotics alter the microbiome in the turkey, reducing the population of certain pathogens, thus lowering the levels of “maintenance” immune transcripts normally expressed in the spleen. Dr. Pratibha Nerurkar and colleagues (University of Hawaii) have recently demonstrated that bitter melon juice (BMJ) improves not only glucose and lipid metabolism, but also prevents weight gain in mice fed a high-fat-diet (HFD) which contains 58% fat. BMJ was also found to improve chronic systemic and hepatic inflammation. Recent mechanistic studies also indicate a role for adipose and intestinal inflammation in the pathophysiology of obesity and Type 2 Diabetes (T2D). The team’s current data demonstrates that BMJ improves macrophage infiltration and inflammation in adipose tissue and intestinal inflammation in mice fed the HFD. BMJ was found to reduce TNF-a and IL-1b. This resulted in reduced insulin signaling and inhibition of insulin resistance, which is mediated via activation of the inflammasome. Dr Nerurkar tested the impact of BMJ in studies using high-fat diet fed mice, and discovered that BMJ reduces fat content and fasting glucose levels. BMJ reduced macrophage infiltration into adipose tissue, and also reduced TLR4 and NF-kB in circulation. Protein levels for leptin, MCP-2 and TNF-a were also reduced. Expression levels of PGE2 and COX-2 in the gut were reduced to normal levels with BMJ, which may be associated with increases in AMPK1 and reduction in TLR4. Lactobacillales present in the cecum was elevated by BMJ. Future studies are planned to understand how BMJ influences gut microbiota, inflammation and obesity-associated T2D. Dr Marie-Louise Ricketts and colleagues (University of Nevada Reno) continued their investigation into the modulation of FXR-target genes in the small intestine and liver by a grape seed procyanidin extract (GSPE), and helped to elucidate a novel molecular mechanism by which GSPE lowers serum triglyceride levels. Their previous studies identified the regulatory effects of GSPE on known intestinal FXR target genes in human colorectal adenocarcinoma (Caco-2) cells, namely apical sodium dependent bile acid transporter (ASBT), ileal bile acid binding protein (IBABP), fibroblast growth factor 15/19 (FGF15/19) and organic solute transporters alpha and beta (OSTa/b. They have now extended these studies in vivo using both C57BL/6 wild type and Farnesoid X receptor (FXR) knockout (FXR-/-) mice. Their results demonstrate that GSPE differentially modulates intestinal FXR-target gene expression in the intestine in an FXR-dependent manner, ultimately resulting in decreased enterohepatic bile acid recirculation. These GSPE-mediated alterations in FXR target-gene expression result in the impairment in intestinal BA up-take into the intestine, transport across the intestine, as well as decreasing the amount of BA that return to the liver via the portal circulation; an observation supported by a significant 46% reduction in serum bile acid levels following GSPE administration in wild type mice. Subsequent studies have also revealed that GSPE causes a significant increase in the mRNA expression of CYP7A1, which results in increased cholesterol 7a-hydroxylase protein expression, and increased conversion of cholesterol into bile acids. The team proposes that the impairment in bile acid absorption caused by GSPE administration may represent another mechanism involved in its’ hypotriglyceridemic effect. Dr Ricketts and colleagues have also investigated the actions of GSPE in vivo, in the presence of the bile acid binding resin, cholestyramine. They have discovered that GSPE and cholestyramine co-administration can exert beneficial metabolic alterations, including decreased triglyceride levels. Dr. Nancy Turner and colleagues (Texas A&M) reported on projects studying the impact of dietary bioactives and other environmental inputs on colon microbiota and how these impact colon and systemic health. She gave an update on the impact of a condensed tannin rich sorghum bran on colon microbiota, plasma metabolites, and microbial metabolites in overweight human subjects. She indicated that metabolites reflective of metabolic syndrome were improved with the sorghum bran intervention and the changes in circulating metabolites of polyphenols were, in part, reflected by changes in the concentration of those molecules in fecal samples. She is also studying the impact of these sorghum polyphenols on serum lipoproteins. She reported on a new study using dried plums, in which the levels of early lesions of colon cancer were reduced by 50% in rats consuming the plum diet. She is sequencing fecal microbial samples and will be studying epigenetic regulation of colon epithelial cell gene expression with samples from this study. She also reported the impact of microgravity and radiation on fecal microbial populations. She will be continuing this work to understand how radiation suppresses apoptosis in colon adult stem cells through epigenetic mechanisms regulated by microbial metabolites. Inflammatory bowel disease rates are increasing worldwide and we now know that colon inflammation is a major driver of colon cancer, and the interaction between the bacteria present in the colon and the epithelial cells can contribute to the inflammatory state of the tissue. In addition, perturbations in microbiota are thought to be linked to either the risk of obesity or to modify the systemic inflammatory tone in overweight/obese subjects. It may be that the link between obesity and colon cancer occurrence is due to the alterations in microbiota and their metabolism that occurs with obesity. The overall purpose of this project is to understand how the intestinal environment (colon and bacteria) is modified in response to biologically active compounds present in our diet, with the main goal being the identification of compounds that are able to suppress inflammation and colon cancer. A secondary goal is to appreciate how diet intercedes in the microbe-induced physiologic changes that occur in overweight/obese subjects. They have demonstrated in a recent publication that butyrate not only enhances histone acetylation, but also suppresses global DNA methylation. Through the combination of butyrate’s effects on histone acetylation and promoter methylation, expression of Tnfrsf25 and Dapk1, which are associated with regulation of apoptosis were upregulated in a colon cancer cell line. The team also demonstrated that polyphenolic molecules in certain varieties of sorghum grain affect the metabolism of microbiota, which leads to changes in fecal concentrations of total short chain fatty acids and butyrate. The changes in microbial metabolism are probably induced by the changes in microbiota detected in feces from rats. Consumption of diets containing brans isolated from black, sumac or high tannin black varieties of sorghum had reduced ratios of Firmicutes to Bacteriodetes. Lower ratios are associated with reductions in both intestinal inflammation and obesity risk in humans. Consumption of the black sorghum bran containing anthocyanidins and the sumac sorghum containing condensed tannins resulted in relatively small increases in injury scores in rats exposed to DSS, an injury model of inflammatory bowel disease. Overweight subjects consuming a breakfast cereal made from sumac sorghum had elevated circulating levels of microbially derived metabolites of plant phenols and aromatic amino acids. Some of these compounds are found at low concentrations in individuals with impaired glucose tolerance, while others are typically suppressed in individuals suffering from ulcerative colitis. These observations were initially made using untargeted metabolomics with plasma samples. However, some of the metabolites most modified in the plasma have now been confirmed to exist in the fecal samples, suggesting the site of generation was the intestine. The same subjects had changes in fecal microbiota, with a distinct elevation in the proportion of Faecalibacterium prausnitzii, a bacteria associated with reduced inflammatory states. Some of their newest work has determined that factors, including diet, weightlessness and radiation, which are characteristic of the environment experienced by individuals during space flight, impact the inflammatory state of the colon. In addition, most factors also induce changes in the microbiota, which may be one of the initiating factors in the alterations in the expression of inflammatory mediators occurring in the colon. Importantly, they found circulating levels for many of these same inflammatory mediators were also altered. These observations suggest that some of the pro-inflammatory responses that occur during spaceflight may originate as a result of the impact of these space environmental factors on the intestine. The last project utilized dried plums to determine whether the impact of this fiber and bioactive compound rich food source would alter colon carcinogenesis. They discovered that including the dried plums in the diet at a level that would correspond to the human equivalent serving size effectively reduced the formation of early pre-neoplastic lesions by 50%. The team are currently in the process of initiating analyses that will determine whether or not the mechanisms involved in the protection are associated with changes in the microbiota and their metabolism. Observations from these studies indicate that part of the protection against intestinal disease and the improvements in systemic health conferred by biologically active compounds is through their effects on the bacterial populations and the byproducts of their metabolism. Alterations to the colon environment induced by these dietary compounds could regulate transcription of genes involved in protection against colon carcinogenesis through epigenetic mechanisms, including histone acetylation and DNA promoter methylation. The benefits derived from these compounds are not constrained to the colon, but may impact overall health because microbial metabolites of the large polyphenolic molecules are being absorbed into systemic circulation. Dr. Tiffany Weir (Colorado State University) reported on her work to develop biological markers to improve assessment of nutrition education programs. The project will use global metabolomic profiling to detect true intake of fruits and vegetables. The overall goal is to identify those biomarkers that not only reflect intake, but that are also associated with health markers (e.g., insulin sensitivity). Stool metabolites obtained from the BENEFIT study were used to segment people into food intake patterns, compared to reported intake patterns. Using the OPLS-DA analytical approach, they were able to discriminate between tertiles of intake. They found that some metabolites were reflective of intake patterns. Currently the team is conducting an intervention study to demonstrate that the biomarkers are indicative of intake in a controlled feeding study. The primary outcome is to validate the OPLS-DA model and to identify other markers present in urine. Secondary measures will include plasma biomarkers (a-hydroxybutyrate) and stool microbiome analysis; additionally, a dried blood spot method is under development as an alternative for plasma collection to measure a-hydroxybutyrate. The team is also conducting other projects to explore the impact of artificial sweeteners, phytoestrogen supplementation, as well as diet and genetic factors on the intestinal microbiome. Dr. Dave Williams and his team (Oregon State University) continue to research dietary chemoprevention of cancer, specifically protection of the fetus/infant from transplacental carcinogens by dietary supplementation with plant phytochemicals or the whole foods from which they were derived. The emphasis continues to be on phytochemicals from cruciferous vegetables primarily indole-3-carbinol (I3C) and sulforaphane (SFN). At the meeting Dr. Williams reported that he is currently trying to understand why a humanized Cyp1B1 mouse model is not responsive to dibenochrysene (DBC) induction of T-cell acute lymphoblastic leukemia (T-ALL). Cyp1B1 is important for adduct formation in the spleen. They found that adducts in fetal lung are present at the same high levels as those found in the maternal lung. Indole-3-carbinol did not affect adduct formation, but Chlorophyllin was able to reduce circulating aflatoxin. They are currently performing a human study to evaluate the pharmacokinetics of benzoalphapyrene (BaP) at the zemptomole level (which is non-hazardous). Other on-going work relates to the evaluation of epigenetic effects on DNA methyltransferases and HDAC (Lys) inhibitors in newborns. I3C causes global DNA methylation levels to return to normal, even in the presence of PAH administration. The team is also evaluating the role of Nrf-2 and effects of maternal dietary SFN in newborns using Nrf-2 KO animals. Initial observations show only a few deaths from T-ALL, but those animals were fed the DBC/SFN diet. Dr. Meijun Zhu and colleagues (Washington State University) have been assessing the impact of bioactives on inflammatory bowel disease and gut microbiota. Impairment in gut epithelial barrier function is a key predisposing factor for inflammatory bowel disease, type 1 diabetes (T1D) and related autoimmune diseases. Dr Zhu’s work has shown that a grape seed extract (GSE) decreases intestinal permeability in IL-10 deficient mice. The GSE was associated with elevated intestinal AOX levels and reduced serum TNF-a levels. Dr Zhu is also studying the effects of goji berry, which has high AOX activity, polyphenols and other beneficial compounds. Dr Zhu has used IL-10 KO mice and the DSS-induced colitis model, and has discovered that DSS causes weight-loss in mice fed a control diet, but goji-berry supplementation helped to prevent as great a weight-loss with DSS, compared to control diet. Goji-berry improved disease scores, but there were no changes in AOX or AOX-markers in the colon. Short chain fatty acids (SCFA) were altered by goji-berry; acetate is reduced while butyrate and isovaleric acid are elevated. Butyrate producing bacteria and butyrate gene expression were increased following goji-berry. There were no significant differences in bacterial groups associated with IBD, but Actinobacteria and Bifidobacteria levels were elevated by goji-berry. There was a reduction in IL-17A, INF-a and TGF-b expression with goji-berry. Results suggest the goji-berry improvement in IBD results from changes in bacterial groups. Dr Zhu has also found that maternal obesity induces impaired glucose tolerance and lower serum insulin levels, inflammation and impaired gut barrier function in female offspring of non-obese diabetic (NOD) mice. Concomitantly, female offspring born to obese dams showed more severe islet lymphocyte infiltration (major manifestation of insulitis) in the pancreas, suggesting enhanced gut permeability in the offspring of obese dams might predispose them to development of T1D. On the other hand, using interleukin-10 (Il10)-deficient mice, they found that 12 weeks of GSE supplementation improved gut barrier function, as indicated by decreased intestinal permeability and increased the colonic goblet cell density and mucin mRNA expression. Immunohistochemical analyses revealed lower ?-catenin accumulation in the crypts of colon tissues of GSE supplemented mice, which was associated with decreased mRNA expression of two down-stream effectors of Wnt/catenin signaling, myelocytomatosis oncogene protein (Myc) and Cyclin D1(ccnd1). Consistently, GSE supplementation decreased the colonic proliferating cell nuclear antigen (PCNA) positive cells, a well-known cell proliferation marker, and weakened extracellular-signal-regulated kinase (ERK1/2) signaling. Data indicate that GSE exerts its beneficial effects in IL-10-deficient mice, probably via inhibiting the Wnt/?-catenin pathway. Objective 2: Elucidate mechanisms of action of dietary toxicants and develop biomarkers for human risk assessment and disease prevention. Dr. Ron Riley (USDA-ARS-Georgia) have initiated studies have to identify the subcellular localization of sphingoid bases and sphingoid base-1-phosphates in mice that are susceptible or resistant to fumonisin-disruption of sphingolipid metabolism and induction of neural tube defects (NTD). Towards this end, a collaborator at Creighton University developed a mouse embryonic fibroblast cell line (MEFs) from fumonisin susceptible and resistant mouse strains. The results show that the bioactive sphingoid base-1-phosphates (Sa1P) are present at higher concentrations in the nucleus than in the cytoplasm and that the levels are highest in the susceptible strain. The protein target of the elevated nuclear Sa1P appears to be histone deacetylase. This is important because human exposure to the histone deacetylase inhibitor, valproic acid, during pregnancy has been shown to cause NTDs. Accumulation of nuclear Sa1P, coupled with a reduction in histone deacetylase activity therefore represents a plausible mechanism for fumonisin induction of NTDs. Additional studies were completed which confirm that humans consuming diets containing high levels of fumonisin have significantly higher levels of sphingolipid metabolites (sphinganine 1-phosphate) in their blood when compared to low fumonisin exposure groups. The levels of sphingolipid metabolites in the blood were significantly correlated with fumonisin B1 in the urine. The results are consistent with the hypothesis that dietary intake of high levels of fumonisin contaminated corn results in disruption of sphingolipid metabolism in humans. Disruption of sphingolipid metabolism is the proximate cause of all the animal diseases known to be caused by fumonisin, including neural tube defects in mice. The incidence of neural tube defects is high in countries where corn is a dietary staple and is likely to be contaminated with high levels of fumonisin and aflatoxin. The results of their biomarker-based studies were provided to the Secretary of Food Security and Nutrition (SESAN) in Guatemala and also other government agencies and non-governmental organizations (Catholic Relief Services Guatemala) along with data on both fumonisin and aflatoxin co-occurrence in Guatemalan corn. As a result of this work, a plan of action has been developed by SESAN and others (World Food Programme) to minimize both aflatoxin and fumonisin exposure in Guatemala. The results were also shared with the US Agency for International Development (USAID) and USDA-FAS in Guatemala. These studies were conducted as part of a collaboration between USDA-TMRU (Athens, GA), Centro de Investigaciones en Nutrición y Salud in Guatemala, Creighton University and Duke University. Dr. Dave Williams and colleagues (Oregon State University) currently focuses on mechanisms of action and biomarkers associated with an important class (3 of the top 10 ATSDR environmental chemicals of concern), polycyclic aromatic hydrocarbons (PAHs), of food-borne carcinogens. These have included molecular biomarkers such as alterations in levels of tumor suppressor genes, DNA adductions, etc., in addition to biological endpoints. Objective 3: Discover and characterize novel dietary compounds that have beneficial or adverse effects on human health. Dr. Bill Helferich and colleagues (University of Illinois) have been assessing the long-term effect of exposure to relevant dietary levels of genistein (GEN) on estrogen receptor-positive (ER+) human breast cancer (MCF-7) progression after GEN withdrawal in athymic mice xenograft model. The following in vivo studies were conducted to determine the effect on the growth of MCF-7 tumors: 1) implantation (19 weeks) and withdrawal (6 weeks) of 17b-estradiol (E2); 2) dietary GEN 500 and 750 ppm during treatment/withdrawal for 23/10 and 15/9 weeks, respectively; and, 3) dietary soy protein isolate (SPI) containing GEN 180 ppm 31/9 weeks of treatment/withdrawal. MCF-7 tumors grew fast in the presence of E2 implantation and abruptly regressed completely after E2 withdrawal. At different rates, dietary GEN alone (500 and 750 ppm) and GEN (180 ppm)-containing SPI stimulated MCF-7 tumor growth. After removal of the stimulus diet, tumors induced by 750 ppm GEN, but not 500 ppm GEN or SPI, regressed completely. The protein expression of epidermal growth factor receptor 2 (HER2) was higher in the GEN- and SPI-induced non-regressing (GINR) tumors compared to MCF-7 and E2 controls. In conclusion, long-term consumption of low GEN doses (?500 ppm) promotes MCF-7 tumor growth and elicits changes resulting in GINR tumors with more aggressive and advanced growth phenotypes. Dr. Marie-Louise Ricketts and colleagues (University of Nevada Reno) have been fractionating the whole GSPE extract to separate out the monomeric, dimeric and trimeric fractions to facilitate examination of which fraction or fractions are responsible for the enhanced transactivation of FXR observed in the presence of the bile acid, CDCA, and GSPE. To date they have isolated both the monomeric and dimeric fractions and have performed TLC analysis of the fractions isolated and have begun HPLC analysis of the monomeric fraction. Once they have performed a more detailed analysis of the fractions isolated they will test the ability of the fractions to transactivate FXR in in vitro transient transfection studies. Objective 4: Increase beneficial or decrease adverse effects of bioactive constituents and microbes in food. Dr. Mendel Friedman and colleagues (USDA-California) discovered that antimicrobial wine marinades behave as broad-spectrum antibiotics against four pathogens, suggesting that they have the potential to be used as food preservatives. The researchers also found that edible antimicrobial films incorporated with carvacrol and cinnamaldehyde inactivated Salmonella Newport on organic leafy greens in closed plastic bags, suggesting that the films have the potential for large-scale use against contaminated leafy greens. They also found that a recently developed commercially available rice hull smoke extract protected mice against endotoxemia, a virulent disease that results mainly from infection by Gram-negative bacteria, suggesting its value as a replacement in food for widely used wood-derived smokes. Additional collaborative studies found that a polysaccharide isolated from the liquid culture of Lentinus edodes (Shiitake) mushroom mycelia containing black rice bran also protected mice against a Salmonella lipopolysaccharide-induced endotoxemia. The USDA research team also discovered that heating of milk spiked with Shiga toxin 2 (Stx2) in a microwave oven at 198 kJ reduced the Stx2 activity, suggesting that microwaving of contaminated food might inactivate the toxin produced by E. coli. The team also found that the interactions of five antimicrobial compounds with monolayers of bacterial phospholipids depended on both the structure of the antimicrobials and the composition of the monolayers, providing insight into the mechanism of the molecular interactions between naturally-occurring antimicrobial compounds and the phospholipids of the bacterial cell membrane that govern activities. The amino acids L-cysteine protected frog embryos against adverse effect of two toxins present in processed food, acrylamide and furan, suggesting that the protective effect of the amino acid merits evaluation in humans. Also during the current reporting period, the tomato glycoalkaloid tomatine reduced the size of transplanted colon tumors in mice by38% after two weeks compared to control, suggesting that the glycoalkaloid may help prevent colon cancer. Dr. Dave Williams (Oregon State University): A major effort this past year has been focused on reducing human health risks from food-borne pathogens and environmental contaminants. I3C is especially potent in reducing the risk to the fetus from exposure in utero to chemical carcinogens ingested in food.

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