Brief Summary of Minutes of Annual Meeting

Report Information: - Annual Meeting Dates: 10/05/06 to 10/07/06 - Period the Report Covers: 10/2005 to 09/2006 Participants: Administrative Advisor Michael Harrington (Colorado), committee members George Bailey (Oregon), Len Bjeldanes (UC Berkeley), Roger Coulombe (Utah), Mendel Friedman (USDA-WRRC Albany, CA), Bill Helferich (Illinois), Jim Pestka (Michigan State), Ron Riley (USDA-ARS Athens, GA), Michael Denison (University of California, Davis) Brief Summary of Minutes of Annual Meeting: W-1122: Beneficial and Adverse Effects of Natural, Bioactive Dietary Chemicals on Human Health and Food Safety Annual meeting of the technical committee, October 5-7, 2006 Monterey, CA The annual meeting was called to order at 0830 Thursday morning, October 5th, 2006. Advisor Michael Harrington provided a report on the current status of funding within USDA for FY 2007. He reported that in the President's budget Hatch funds have the potential for significant change. These changes may include: 1. Making a portion of Hatch funds competitive 2. Create National Institutes of Food and Agriculture Research 3. Focus on problem-base areas like the NIH These potential changes will require significant additional discussion. Further details of the potential changes can be found at www.create-21.org. After Dr. Harrington's comments the annual reports were given as follows: Technical Reports Bailey, George - Oregon State University Bjeldanes, Len - University of California at Berkeley Coulombe, Roger - Utah State University Pestka, Jim - Michigan State University Helferich, Bill - University of Illinois Friedman, Mendel - USDA-ARS Albany Denison, Mike - University of California Davis Riley, Ron - USDA-ARS Athens Discussion on the revised new project plan for the next five years were discussed and changes were made to the draft document. Additional details will be added by Dr. Coulombe and will be sent directly to him at rogerc@cc.usu.edu. The W1122 project plan is due July, 2007. The regular business portion of the meeting commenced Friday morning. Napa California was selected as the site for the 2007 meeting (October 3,4,,&5, 2007. For 2007, Mike Denison would serve as Secretary, Bill Helferich as Chair-elect and Ron Riley as Chair. The meeting was adjourned at around 1200 on October 6, 2006.

ACCOMPLISHMENTS FOR THE ENTIRE SPAN OF THE PROJECT ARE SUMMARIZED BEGINNING WITH 2006 The activities described below have addressed specific components of the W1122 Multistate project as outlined in the milestones document for the project. Many of the activities have been collaborative efforts among W1122 participants and all have benefited from the critical review provided by all particpants at the annual meetings and throughout the year. Over the five year span of the project, the activities described below have been documented by over 300 publications and numerous reports and data provided to industry, consumers, and authorative bodies such as the USFDA, WHO/FAO, International Agency for Research on Cancer, Council for the Advancement of Science and Technology, etc. Participants from Oregon, Michigan, Utah, Berkeley and USDA-ARS have played leadership roles in the Society of Toxicology (SOT)and have organized symposia and workshops that have promulgated the W1122 message and activities at the annual meetings of SOT and other international societies and conferences including the Gordon Research Conferences. OBJECTIVE 1. Determine the cellular and molecular modes of action by which bioactive chemicals in food protect against human diseases such as cancer, inflammation and microbial infection. 2006 Continuing research to define the interrelationships between carcinogen (dibenzo(a,l)pyrene, DBP) dose, chlorophyll (Chl) dose, maximal target organ DNA adduction, and final tumor outcome was conducted by the group in Oregon. The results show that in liver at carcinogen doses and tumor levels relevant to human cancer rates, natural chlorophyll can provide potent inhibition of DBP tumorigenicity at dietary Chl concentrations well within the range found in spinach. These findings provides strong evidence for the beneficial effects of dietary CHl and will be useful to nutritionist and food safety scientists worldwide. A collaborative tumor study involving the W1122 team in Oregon and USDA-ARS - Albany showed that tomatine, a chemical found in tomato leaves, given during the period of carcinogen treatment, significantly inhibited tumor incidence in liver and stomach. This is an important finding that further demonstrates the importance of bioactive chemicals in foods. The group at Michigan conducted and published research showing that consumption of the polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) suppressed activation of signaling processes that modulate inflammatory gene expression in macrophages. These findings are important because they provide insight for biomedical researchers into the mechanisms for PUFA suppression of proinflammatory cytokine expression. The group at USDA-ARS in Athens conducted and published the results of research activities that showed that the nephrotoxicity of fumonisins in rats is a result of the preferential accumulation of both fumonisins, and sphingoid bases and sphingoid base 1-phosphates. The results provide a plausible explanation for why rat kidney is so much more sensitive that rat liver to fumonisin toxicity. This finding is important because nephrotoxicity in rat is the critical effect used for establishing the current tolerable daily intake set by the WHO/FAO Joint Expert Committee on Food Additives. The group at USDA-ARS Athens has developed a model system for studying the mechanistic basis for Fusarium verticillioides-induced corn seedling desease and the role of fumonisins as virulence factors. The model may prove useful for developing a better understanding of the basis for seedling resistance to F. verticillioides. The Utah group cloned, expressed and characterized a turkey liver CYP 1A5 (1587 bp ; 528 amino acids) that has high AFB1-epoxidation activity, that may be responsible, at least in part, for the well-known hypersensitivity of turkeys to AFB1. This may be the first P450 cloned and sequenced from turkeys. These results provide the framework for identifying allelic variants of this biochemically important CYP gene in poultry and the basis for breeding for increased resistance to aflatoxins in farm raised turkeys. 2005 to 2002 Research activities by W1122 team members in Oregon included tumor studies comparing the cancer chemopreventive efficacy of natural chlorophyll (Chl) with its water soluble food dye derivative chlorophyllin (CHL). The research resulted in several key publications containing the information needed by risk managers to implement interventions to reduce liver cancer risk in high risk populations. Research activities by the group at Utah State University found that dietary butylated hydroxytoluene (BHT) protects against nearly all clinical signs of aflatoxicosis in turkeys, with concentrations as low as 100 ppm BHT protecting against some signs of aflatoxicosis. These findings were published and the information provides the basis for developing interventions to reduce the economic losses incurred by aflatoxin poisoning. Research activities by the group in Georgia in collaboration with researchers from the University of Nebraska found that neural tube defects could be induced in LM/Bc mice and that the mechanism of action involved disruption of the folate transporter. This information was published and filled an important gap in the fumonisin risk assessment conducted by the WHO/FAO Joint Expert Committee on Food Additives. The W1122 group in Oregon showed that chlorophyll and the synthetic derivative chlorophyllin had cancer protective properties which were related to inhibition of the environmental carcinogens dibenzopyrene and aflatoxin. A collaborative study between USDA-ARS Albany and the group in Oregon found that tomatine, an alkaloid present in tomatoes, was nontoxic at high levels using trout, paving the way for long-term studies on the efficacy of tomatine to modulate tumor formation or progression. The Utah State team found that dietary butylated hydroxytoluene (BHT) protects turkeys against aflatoxicosis and the mechanism appears to involve inhibition of epoxide formation. This work sets the stage for more in depth studies of BHT as a intervention strategy. USDA-ARS Albany found that extracts of pigmented rice brans were much stronger inhibitors of tumor promotion than extracts from nonpigmented white rice cooking varieties and studies on green tea catechins were shown to have potent antibactericidal activity. The W1122 group at Michigan State found that omega-3 fatty acids found in fish oil were effective at suppressing an experimental model of a common kidney disease. In an investigation by the group at Berkeley it was found that DIM stimulated the activity of an estrogen receptor- responsive reporter by up to 40 fold. The stimulatory effect was abolished with an estrogen receptor antagonist. In a separate study it was found that DIM is a potent antagonist of androgen function in prostate tumor cells. These findings show that DIM is a mechanistically novel activator of the estrogen receptor and establish DIM as a unique bifunctionally active hormone disruptor. W1122 researchers at Michigan found that the two main omega-3 polyunsaturated fatty acids in fish oil, docosahexaenoic acid and eicosapentaenoic acid, retard progression of primary IgA nephropathy and also significantly reduce IgA secretion by spleen cells in mice induced by the tricothecene mycotoxin deoxynivalenol (DON). They also showed that DON affects expression of multiple genes that may contribute to its immunotoxic effects and this expression profile can be affected by diets containing omega-3 fatty acids. In anticipation of future studies, researchers at Oregon assessed the dose-dose interactions between dietary chlorophyllin (CHL) and dibenzo(a,1)pyrene (DBP) in the trout multi-organ tumorigenesis model. Overall, CHL-mediated reduction in target organ DNA adduction was found to be a predictive biomarker for eventual reduction of tumor risk in both target organs (stomach and liver). In collaboration with Oregon researchers, the group at Utah initiated a study introducing an efficient AFB1 metabolizing enzyme into plants. The CYP isoform appears to be a "pure epoxidator" in that it forms no other non-epoxidated metabolites. Various CYP-containing gene cassettes are being expressed into E. coli and into Agrobacterium for later tranfection into tobacco and maize. OBJECTIVE 2. Determine cellular effects and molecular mechanisms of natural and induced toxicants in food for human risk assessment and disease prevention. 2006 Research conducted by the Oregon group used an IRB approved ultra-low dose 14C-AFB1 (5 nCi, 30 ng) (provided by USDA-ARS Athens) to assess AFB1 uptake, distribution, and elimination in humans. This study will provide the most complete pharmacokinetic analysis ever conducted for AFB1 in humans. It also has set the stage for examination of CHL and Chl effects on AFB1 bioavailability in humans, which is currently in progress. The group in Michigan continued their in depth probe to define the molecular mechanisms by which deoxynivalenol alters immune response. They found (i) deoxynivalenol (DON) activated competing apoptotic and survival pathways in macrophages and (ii) extremely rapid association and activation of PKR, Hck, ERK was detected in ribosomes from DON-treated RAW 264.7 cells. These observations suggest that, following DON interaction, signaling pathways are affected and that the ribosome functions as signal transducer and mediates activation and binding of a number of protein kinases These interactions can potentially affect transcriptional and translational regulation of cytokine and chemokine genes as well as apoptosis induced by DON. 2005 to 2002 Microarray studies in rainbow trout conducted in Oregon showed that the gene expression effects of aflatoxin B1 in rainbow trout strongly resemble those reported in human and rodent hepatocellular carcinoma. The published results validate that the trout model can be used to accurately evaluate cancer risk in humans and at a cost that is much less than conducting similar studies in rodents. Research conducted by the Michigan group showed that deoxynivalenol interfered with the immune response to reovirus infection. The subsequent publication demonstrated the likely mechanism of action and established the need for risk assessors to consider the occupational hazards associated with exposure to deoxynivalenol by farm workers. Oregon State and Berkeley are both conducting research activities to elucidate the effects of the indole-3-carbinol dimer (DIM) on tumor formation in various animal models. Oregon team members developed a trout gene chip and found that tumor promotion acted through an estrogenic pathway and continued after stopping DIM treatment, thus indicating no requirement for chronic exposure. The Berkeley group found that DIM has immune activating and antiangiogenic activity which reduced some tumors in other animal models. These results from emphasize the complex biological interactions which need to be considered with dietary supplements such as DIM. The Michigan group showed that the sensitivity of human white blood cells to the mycotoxin deoxynivalenol (DON or vomitoxin) was correlated with a specific protein kinase. Humans are 4-fold more sensitive to this kinase than are mice and DON sensitivity was found to vary among individuals, perhaps due to both genetic and non-genetic factors. The Michigan group found that deoxynivalenol (DON) induces a signaling cascade in the murine macrophage model (RAW 264.7 cells) that results in elevated TNF-alpha and MIP-2 gene expression. They also reported on studies showing that in peripheral mononuclear blood leukocytes, IL-6 and IL-8 were significantly induced by DON as was TNF-alpha. The group at Utah found that the age-related susceptibility of poultry to AFB1 may be due to the fact that microsomal AFB1 activation was most efficient in the youngest birds while the activity of hepatic cytosolic glutathione S-transferases were deficient in the youngest age group but higher in the older groups. The extreme sensitivity of young turkeys to the toxic effects of AFB1 may result from more efficient activation. The group at USDA-ARS Athens in collaboration with the group in Oregon found that dietary fumonisins are potent promoters of aflatoxin-initiated liver tumor formation in trout. This is important because aflatoxin and fumonisin co-occur in maize throughout the world. OBJECTIVE 3. Detect and identify new natural or induced bioactive compounds in foods that have beneficial or adverse effects on human health. 2006 A collaborative study by the group at Michigan and the group at Berkeley found that diindolylmethane (DIM) enhances immune response against reovirus gut infection. Overall, the results suggest that DIM enhanced both clearance of reovirus from the GI tract and the subsequent mucosal IgA response and have uncovered strong immune stimulating activities of DIM, which might contribute to the cancer inhibitory effects of this indole. This is an important observation that provides new insights into disease causation and prevention. The group at Berkeley found that DIM is a novel mitochondrial H+-ATP synthase inhibitor that can induce p21 expression by induction of oxidative stress in human breast cancer cells. These findings add additional support to the mechanistic understanding of this unique group of foodborne bioactive compounds. In a collaborative study with Korean scientists, the group at USDA-ARS Albany determined inhibitory effects of extracts of pigmented black rice brans on in vitro allergic reactions. The results suggest that polyphenol-rich pigmented rice brans merits further evaluation as part of a human diet to ascertain their potential to protect against allergic diseases such as hay fever and asthma. The group in Michigan found that trichothecene-mediated immunosuppression increased sensitivity of a host to enteric virus infection. Thus, in addition to systemic immune dysregulation trichothecenes also appear to interfere with mucosal host resistance. 2005 to 2002 Research was conducted by the group in Berkeley which showed that 3,3'-diindolymethane (DIM) could interfere with the signaling cascade necessary for angiogenesis. Publications documented the underlying mechanism provided medical researcher with a new mode of action for this intriguing dietary component. This work is important because it provides a new avenue of research that could lead to an improved understanding of tumor promotion. An improved HPLC method was developed by the USDA-ARS group in Albany and used to quantify potentially economically important chemicals in pepper fruit. This work was important because these improved methods will be used by the food industry to better evaluate food products and at lower cost to consumers. The USDA-ARS group in Athens developed an analytical method for detection of sphinganine-1-phophate in serum of animals exposed to subtoxic doses of fumonisins. Studies characterized a new sphingoid base metabolite in renal cells treated with fumonisin and suggested that this sphingoid could play an important role in fumonisin-induced renal toxicity. The group at Colorado found that curcumin, the yellow-coloring pigment in turmeric, inhibits biofilm formation and toxin production in Pseudomonas aeruginosa, which causes lung disease symptoms in cystic fibrosis. This was accomplished through inhibition of quorum sensing, a communication mechansim in the bacterium. Curcumin did not kill the bacteria, which remained alive, but were no longer capable of causing disease. The group at Colorado found that light and dark culture conditions and cell aggregate size, played an important role in growth of Hypericum perforatum L (St. Johns wort ) and production of its bioactive component, hypericin, in cell suspension cultures. A major gene termed Hyp-1 encoding for hypericin biosynthesis was cloned and characterized from H. perforatum L. cell cultures. In a separate study, the group at Colorado found that (-)-catechin, a root-secreted phytotoxin, contributes to Centaurea maculosas (spotted knapweed) invasive behavior in the rhizosphere. (+)-Catechin had antibacterial activity against root infesting pathogens while (-)-catechin did not. Results suggest that each enantiomer of racemic catechin contributes separate properties for plant aggression and defense. The W1122 researchers in Idaho identified several bioactive compounds in studies of wild and cultivated Vaccinium including blueberries, huckleberries, and cranberries. The wild Vaccinium species were highest in anthocyanin content. Of the aglycons studied, delphinidin and cyaniding were consistently found in the greatest amount while quercitin was typically found to be the most abundant of the flavonols. OBJECTIVE 4. Ascertain how agricultural production and food processing may influence production/stability of natural bioactive chemicals. 2006 The group at USDA-ARS Albany investigated the inhibition of Clostridium perfringens spore germination and outgrowth by the biopolymer chitosan during abusive chilling of cooked ground meat and turkey obtained from a retail store. The results suggest that incorporation of 3% chitosan into ground beef or turkey may reduce the potential risk of C. perfringens spore germination and outgrowth during abusive cooling. The USDA-ARS group in Athens evaluated the histological changes in rodent tissues following consumption of diets prepared by extrusion cooking from fumonisin-contaminated corn grits. It was found that extrusion cooking reduces in vivo toxicity if 10% glucose is added to the grits before extrusion and if the process reduces detectable fumonisin concentrations below a critical value. Extrusion without glucose supplementation had no beneficial effect. 2005 to 2002 Research was conducted by the USDA-ARS group in Athens in collaboration with food processors which showed that baking cookies and crackers did not appreciably destroy DON, but it was degraded or otherwise "lost" during the frying of donuts. These findings were provided to the USFDA and industry risk assessors to be used in the determination of the adequacy of current regulatory limits for deoxynivalenol. Maize samples analyzed the the USDA-ARS Athens group from highland (> 1700 m) areas in Guatemala were found to be far less contaminated with fumonisin and Fusarium verticillioides than lowland samples. This information is important because there is a concern that fumonisin exposure could contribute to neural tube defects in Guatemala, where NTD incidence is often very high. An exposure assessment was conducted and the findings were provided to risk managers in Guatemala to be used for the purposes of minimizing fumonisin exposure. The group at Davis conducted a survey of literature reports which attempted to compare the beneficial (detrimental) effects of organic vs. traditional agriculture in regard to human health. From a scientific viewpoint, few or none of the studies appeared to be conclusive and there was a significant lack of quantitative data. The Illinois group compared estrogenicity of minimally processed soy-based products consumed in Asian countries and more processed soys or pure isoflavones. The degree of soy flour processing affected the estrogenicity of products although all were compared to a constant level of the isoflavone genistein. Thus, refined products were more estrogenic than those which are minimally processed. The findings suggest that for postmenopausal women with estrogen-dependent breast cancer, the consumption of foods containing soy flour rather than refined products is more advisable. The USDA-ARS Athens group analyzed for fumonisins in maize grown in lowland and highland communities in Guatemala. Fumonisin often exceeded the maximal tolerable daily intake established by the WHO. Lowland corn, which is imported and used in the highlands, was found to be a source of greater fumonisin content than that grown locally in the highlands. The W1122 researches at California, Davis found that the fungicide metalaxyl appears to be a promising candidate for reducing fumonisin levels as cultures of Fusarium verticillioides grown in media containing the fungicide showed normal fungal growth but significantly reduced levels of fumonisins. The USDA-ARS Albany group conducted and published a comprehensive review of the chemical and biological basis of the formation in food and the toxicological effects of acrylamide. (WRRC) OBJECTIVE 5. Identify and investigate modes of action of food-borne factors which may reduce the impact of dietary carcinogens. 2006 The group in Illinois found that Genistein (GEN) can negate the aromatase inhibitory effects of letrozole (LET) on E-dependent tumor growth. It was concluded that dietary GEN increased the growth of implanted MCF-7Ca tumors in mice. Moreover, GEN negated the inhibitory effect of LET on MCF-7Ca tumor growth. These findings are significant because estrogen-dependent breast tumors, which express aromatase and can locally synthesize estrogens, are good candidates for successful aromatase therapy; however, the ability of dietary GEN to reverse the inhibitory effect of LET on tumor growth shows that this diet-drug interaction could adversely impact the course of breast cancer therapy. As previously shown for tamoxifen, caution is warranted for consumption of dietary GEN by postmenopausal women with estrogen-dependent breast cancer taking LET treatment. 2005 to 2002 Research was conducted by the group at Illinois to show that the soy chemical genestein acts in an additive manner with estrogen to stimulate growth of MCF-7 tumor growth in athymic mice. This finding is important because the safety of food products containing high levels of genestein is uncertain and establishing a level of exposure that is safe is a critically important issue in developed countries. The group in Illinois conducted a study to determine the ability of dietary genistein to negate or overwhelm the effectiveness of tamoxifen (TAM). In the presence of TAM estradiol implants, no growth of estrogen dependent tumor growth was observed. When genestein was present in the diet a significant increase in tumor growth was observed. Thus, genestein appears to negatively affect the efficacy of TAM; a widely used treatment for breast cancer. Other studies by the Illinois group found that diets containing soy flour can reduce the bioavailability of genestein or that there are other bioactive products in soy that can alter the effect of genestein. The group at Oregon showed that green and white teas effectively suppress tumor development in two mouse models of colorectal cancer. Both teas and molecular studies provide evidence that this is, at least in part, suppressing beta-catenin expression in normal intestinal mucosa.

ONLY PUBLICATIONS REPORTED AT THE 2006 MEETING ARE LISTED Allred, C. A., Allred, K.F., Ju, Y.H., Doerge, D.R., and Helferich, W.G. (2004) Soy processing influences growth of estrogen-dependent breast cancer tumors. Carcinogenesis 25(9):1649-1657 Allred, C.A., Allred, K.F., Ju, Y.H., Doerge, D.R., Schantz, S., Korol, D., and Helferich, W.G. (2004) Dietary genistein results in larger MNU-induced, estrogen-dependent mammary tumors following ovariectomy of Sprague-Dawley rats. Carcinogenesis 25:211-218. Allred, C.D., Twaddle, N.C., Allred, K.F., Churchwell, M.I., Ju, Y.H., Helferich, W.G., and Doerge, D.R. (200X) Soy processing affects metabolism and disposition of dietary isoflavones in ovariectomized Balb/c mice. J. Ag and Food Chem. (In Press) Brew, C.T., Aronchik, I., Hsu, J.C., Sheen, J.H., Dickson, R.B., Bjeldanes, L.F., Firestone, G.L. (2006) Indole-3-carbinol activates the ATM signaling pathway independent of DNA damage to stabilize p53 and induce G1 arrest of human mammary epithelial cells. Int. J. Cancer. 118(4):857-68. Chang, X., Firestone, G.L., Bjeldanes, L.F. (2006) Inhibition of growth factor-induced ras signaling in vascular endothelial cells and angiogenesis by 3,3'-diindolylmethane. Carcinogenesis. 27(3):541-50. Coulombe, R.A., Guarisco, J.A., Klein, P.J. and J.O. Hall (2005) Chemoprevention of aflatoxicosis in poultry by dietary butylated hydroxytoluene. Animal Feed Science and Technology 121: 217-225. Friedman, M. (2006) Nutritional evaluation of D-amino acids. In D-Amino Acids: A New Frontier in Amino Acid and Protein Research - Methods and Protocols, R. Kono and G. H. Fisher (Eds.), Nova Science Publishers, Happauge, New York, Chapter 4. Friedman, M., Buick, R., and Elliott, C. T. (2006) Antimicrobial activities of plant compounds against antibiotic-resistant Micrococcus luteus. Int. J. Antimicrob. Agents. 28: 156-158. Friedman, M., Henika, P. R., Levin, C. E., and Mandrell, R. W. (2006) Antimicrobial wine formulations against the foodborne pathogens Escherichia coli O157: H7 and Salmonella enterica. J. Food Sci. 71: M245-251. Friedman, M., Henika, P. R., Levin, C. E., Mandrell, R. E., and Kozukue, N. (2006) Antimicrobial activities of tea catechins and theaflavins and tea extracts against Bacillus cereus. J. Food Prot. 69: 354-361. Friedman, M., Levin, C. E., Choi, S.-H., Kozukue, E., and Kozukue, N. (2006) HPLC analysis of catechins, theaflavins, and alkaloids in commercial teas and green tea dietary supplements: comparison of water and 80% ethanol/water extracts. J. Food Sci. 71: C328-C337. Gong Y, Firestone, G.L., Bjeldanes,L.F. (2006) 3,3'-Diindolylmethane (DIM) is a novel topoisomerase II{alpha} catalytic inhibitor that induces S phase retardation and mitotic delay in human hepatoma HepG2 cells. Mol Pharmacol. Mol. Pharmacol. 69(4):1320-7. Gong, Y., Sohn, H., Xue, L,. Firestone, G.L., Bjeldanes, L.F. (2006) 3,3'-Diindolylmethane is a novel mitochondrial H(+)-ATP synthase inhibitor that can induce p21(Cip1/Waf1) expression by induction of oxidative stress in human breast cancer cells. Cancer Res. 66(9):4880-7. Hsu JC, Dev A, Wing A, Brew CT, Bjeldanes LF, Firestone GL. (2006) Indole-3-carbinol mediated cell cycle arrest of LNCaP human prostate cancer cells requires the induced production of activated p53 tumor suppressor protein. Biochem Pharmacol. 2006 Sep 11; [Epub ahead of print]. Hsu, J.C., Zhang, J., Dev, A., Wing, A., Bjeldanes, L.F,. Firestone, G.L. (2005) Indole-3-carbinol inhibition of androgen receptor expression and down-regulation of androgen responsiveness in human prostate cancer cells. Carcinogenesis. 26(11): 1896-904. Islam, Z., and Pestka, J. J. (2006). LPS priming potentiates and prolongs proinflammatory cytokine response to the trichothecene deoxynivalenol in the mouse. Toxicol. Appl. Pharmacol. 211(1), 53-63. Islam, Z., Gray, J. S., and Pestka, J. J. (2006). p38 Mitogen-activated protein kinase mediates IL-8 induction by the ribotoxin deoxynivalenol in human monocytes. Toxicol. Appl. Pharmacol. 213(3), 235-244. Islam, Z., Harkema, J. R., and Pestka, J. J. (2006). Satratoxin G from the black mold Stachybotrys chartarum evokes olfactory sensory neuron loss and inflammation in the murine nose and brain. Environ. Health Perspect. 114(7), 1099-1107. Jia, Q., and Pestka, J. J. (2005). Role of cyclooxygenase-2 in deoxynivalenol-induced immunoglobulin a nephropathy. Food Chem. Toxicol. 43(5), 721-728. Jia, Q., Zhou, H. R., Shi, Y., and Pestka, J. J. (2006). Docosahexaenoic acid consumption inhibits deoxynivalenol-induced CREB/ATF1 activation and IL-6 gene transcription in mouse macrophages. J. Nutr. 136(2), 366-372. Ju, Y. H., Allred K.F., Allred, C.D., and Helferich, W.G. (200X) The Soy Isoflavone, Genistein, Stimulates the Growth of Human Breast Cancer Cells In Vivo in the Presence of Low Plasma Levels of Estradiol. (Submitted) Carcinogenesis Ju, Y. H., Fultz J, Allred K.F., Doerge D.R., and Helferich, W.G. (200X) Effects Of Dietary Daidzein And Its Metabolite, Equol, At Physiological Concentrations On The Growth Of Estrogen-Dependent Human Breast Cancer (MCF-7) Tumor Implanted In Ovariectomized Athymic Mice. (In Press) Carcinogenesis Ju, Y.H., Clausen, L.M., Almada, A.L., and Helferich, W.G. (2004) Beta$-sitosterol, $Beta-sitosterol glucoside, and a mixture of $Beta- sitosterol and $-sitosterol glucoside modulate the growth of estrogen-responsive breast cancer cells in vitro and in ovariectomized athymic mice. J. Nutr. (In Press) Jubert, C and Bailey, G. (200x). Large-Scale Isolation of Chlorophyll a and b from Spinach by Counter-Current Chromatography. Journal of Chromatography A, (submitted). Juneja, V. K., Thippareddi, H., and Friedman, M. (2006) Control of Clostridium perfringens in cooked ground beef by carvacrol, cinnamaldehyde, thymol, or oregano oil during chilling. J. Food Prot. 69: 1546-1551. Juneja, V. K., Thippareddi, H., Bari, L., Inatsu, Y., Kawamoto, S., and Friedman, M. (2006) Chitosan protects cooked ground beef and turkey against Clostridium perfringens spores during chilling. J. Food Sci. 71: M236-M240. Kinser, S., Li, M., Jia, Q., and Pestka, J. J. (2005). Truncated deoxynivalenol-induced splenic immediate early gene response in mice consuming (n-3) polyunsaturated fatty acids. J. Nutr. Biochem. 16(2), 88-95. Kozukue, N., Han, J. S., Kozukue, E., Lee, S. J., Kim, J. A., Lee, K. R., Levin, C. E., and Friedman, M. (2005) Analysis of eight capsaicinoids in peppers and pepper-containing foods by high-performance liquid chromatography and liquid chromatography-mass spectrometry. J. Agric. Food Chem. 53: 9172-9181. Kwon, D., Yoon, S., Carter, O., Bailey, G.S., Dashwood, R.H. (200x) Antioxidant and antigenotoxic activities of Angelica keiskei, Oenanthe javanica and Brassica oleracea in the Salmonella mutagenicity assay and in HCT116 human colon cancer cells. BioFactors, in press Li, M., Cuff, C. F., and Pestka, J. (2005). Modulation of murine host response to enteric reovirus infection by the trichothecene deoxynivalenol. Toxicol. Sci. 87(1), 134-145. Li, M., Cuff, C. F., and Pestka, J. J. (2006). T-2 toxin impairment of enteric reovirus clearance in the mouse associated with suppressed immunoglobulin and IFN-gamma responses. Toxicol. Appl. Pharmacol. 214(3), 318-325. Li, M., Harkema, J. R., Islam, Z., Cuff, C. F., and Pestka, J. J. (2006). T-2 toxin impairs murine immune response to respiratory reovirus and exacerbates viral bronchiolitis. Toxicol. Appl. Pharmacol. (in press) Mbandi, E., and Pestka, J. J. (2006). Deoxynivalenol and satratoxin G potentiate proinflammatory cytokine and macrophage inhibitory protein 2 induction by Listeria and Salmonella in the macrophage. J. Food Prot. 69(6), 1334-1339. Muthyala, R.S., Ju, Y.H., Sheng, S., Williams, L.D., Doerge, D.R., Katzenellenbogen, B.S., Helferich, W.G., and Katzenellenbogen, J.A. (2004) Equol, a natural estrogenic metabolite from soy isoflavones: convenient synthesis and resolution of R- and S-equol and their biological activity through the estrogen receptors alpha and beta. Bioorganic & Medicinal Chemistry 12(6): 1559-567. Nam, S. H., Choi, S. P., Kang, M. Y., Koh, H. J., Kozukue, N., and Friedman, M. (2006) Antioxidative activities of bran extracts from twenty one pigmented rice cultivars. Food Chem. 94: 613-620. Orner GA., Roebuck BD., Dashwood RH., Bailey GS. 2006. Post-initiation chlorophyllin exposure does not modulate aflatoxin-induced foci in the liver and colon of rats. Journal of Carcinogenesis 2006, 5:6. Pestka, J. J., and Smolinski, A. T. (2005). Deoxynivalenol: toxicology and potential effects on humans. J. Toxicol. Environ. Health B Crit Rev. 8(1), 39-69. Pestka, J. J., Uzarski, R. L., and Islam, Z. (2005). Induction of apoptosis and cytokine production in the Jurkat human T cells by deoxynivalenol: role of mitogen-activated protein kinases and comparison to other 8-ketotrichothecenes. Toxicology 206 (2), 207-219 Pestka, J., and Zhou, H. R. (2006). Toll-like receptor priming sensitizes macrophages to proinflammatory cytokine gene induction by deoxynivalenol and other toxicants. Toxicol. Sci. 92(2), 445-455. Pratt, M. M., Reddy, A. P., Hendricks, J.D., Pereira, C., Kensler, T.W., and Bailey, G.S. (2006). The importance of carcinogen dose in chemoprevention studies: quantitative interrelationships between, dibenzo[a,l]pyrene dose, chlorophyllin dose, target organ DNA adduct biomarkers, and final tumor outcome. Carcinogenesis doi: 10.1093/carcin/bgl174 Reed, K.M., Mendoza, K.M. and R. A. Coulombe, Jr. (2006). Structure and genetic mapping of the Cytochrome P4501A5 gene in the turkey (Meleagris gallopavo). Cytogenetics and Genome Research (in press). Riby, J.E., Xue, L., Chatterji, U., Bjeldanes, E.L., Firestone, G.L., Bjeldanes, L.F. (2006) Activation and potentiation of interferon-g signaling by 3,3-diindolylmethane in MCF-7 breast cancer cells. Mol. Pharmacol. 69(2):430-9. Riley RT, Voss KA, Speer M, Stevens VL, Gelineau-van Waes J. (2006) Fumonisin inhibition of ceramide synthase: A possible risk factor for human neural tube defects. In, Y. Hirabayashi , A. Merrill, and Y. Igarashi (Eds) Sphingolipid Biology, pp. 345-362, Springer Verlag, Tokyo. Riley RT, Voss KA. (2006) Differential sensitivity of rat kidney and liver to fumonisin toxicity: Organ specific differences in toxin accumulation and sphingoid base metabolism. Toxicological Science 92: 335-345. Riley, R.T., Torres, O.A., Palencia, E. (2006) International shipping of fumonisins from maize extracts on C18 sorbent. Food Additives and Contaminants. 23: 826-832. Selvaraj V, Zakroczymski MA, Naaz A, Mukai M, Ju YH, Doerge DR, Katzenellenbogen JA, Helferich WG, Cooke PS (2004) Estrogenicity of the isoflavone metabolite equol on reproductive and non-reproductive organs in mice. Biology of Reproduction 71:966-972. Sharma, R.P., He, Q. and Riley, R.T. (2005) Lupus-prone NZBWF1/J mice, defective in cytokine signaling, are resistant to fumonisin hepatotoxicity despite accumulation of liver sphinganine. Toxicology 216: 59-71. Shi, Y., and Pestka, J. J. (2006). Attenuation of mycotoxin-induced IgA nephropathy by eicosapentaenoic acid in the mouse: dose response and relation to IL-6 expression. J. Nutr. Biochem. 17(10), 697-706. Simonich, M.T., Egner, P.E., Roebuck, B.D., Orner, G., Jubert, C., Pereira, C., Groopman, J.D., Kensler, T.W., Dashwood, R.H., Williams, D., and Bailey, G.S. (200x). Natural chlorophyll inhibits aflatoxin B1 induced multi-organ carcinogenesis in the rat. Carcinogenesis, (submitted) Simonich, M.T., McQuistan, T., Jubert, C., Pereira, C., Hendricks, J.D., Dashwood, R.H., Williams, D., and Bailey, G.S. (200x). Natural chlorophyll inhibits dibenzo[a,l]pyrene-induced multi-organ carcinogenesis in the rainbow trout. Carcinogenesis, (submitted). Smolinski, A. T., and Pestka, J. J. (2005). Comparative effects of the herbal constituent parthenolide (Feverfew) on lipopolysaccharide-induced inflammatory gene expression in murine spleen and liver. J. Inflamm. (Lond) 2, 6. Staub, R.E., Onisko, B., Bjeldanes, L.F. (2006) Fate of 3,3'-diindolylmethane in cultured mcf-7 human breast cancer cells. Chem Res Toxicol. 19(3):436-42, Sundar SN, Kerekatte V, Equinozio CN, Doan VB, Bjeldanes LF, Firestone GL. (2006) Indole-3-Carbinol (I3C) selectively uncouples expression and activity of estrogen receptor subtypes in human breast cancer cells. Mol Endocrinol. 2006 Aug 10; [Epub ahead of print]. Tilton, S.C., Hendricks, J.D., Orner, G.A., Pereira, C.B., Bailey, G.S., and Williams, D.E. (200x) Gene expression analysis during tumor enhancement by the dietary phytochemical, 3,3-diindolylmethane, in rainbow trout. (Submitted) Urraca, J. L., ito-Pena, E., Perez-Conde, C., Moreno-Bondi, M. C., and Pestka, J. J. (2005). Analysis of zearalenone in cereal and Swine feed samples using an automated flow-through immunosensor. J. Agric. Food Chem. 53(9), 3338-3344. Van Vleet, T.R., Watterson, T.L., Klein, P.J., and R.A. Coulombe, Jr. (2006). Aflatoxin B1 alters the expression of p53 in cytochrome P450-expressing human lung cells. Toxicological Sciences. 89, 399-407. Vivanti, V., Finotti, E., and Friedman, M. (2006) Level of acrylamide precursors asparagine, fructose, glucose, and sucrose in potatoes sold at retail in Italy and in the United States. J. Food Sci. 71: C81-C85. Voss KA Gelineau-van Waes, Riley RT. (2006) Fumonisins: current research trends in developmental toxicology. Mycotoxin Research 22, 61-69. Voss KA, Liu J, Anderson SP, Dunn C, Miller JD, Owen JR, Riley RT, Bacon CW, Corton JC. (2006)Toxic effects of fumonisin in mouse liver are independent of the peroxisome proliferator-activated receptor ±. Toxicological Science 89:108-119. Voss KA, Norred WP, Meredith FI, Riley RT, Saunders DS. (2006) Fumonisin concentration and ceramide synthase inhibitory activity of corn, masa and tortilla chips. Journal of Toxicology and Environmental Health (Part A) 69:1387-1397. Voss KA, Riley RT, Dunn C, Corton JC. (2006) The role of tumor necrosis factor a and the peroxisome proliferator-activated receptor a in modulating the effects of fumonisin in mouse liver. Toxicology 222:165-174. Voss KA, Riley RT, Gelineau van-Waes JB. (2005) Trends in fumonisin research: recent studies on the developmental effects of fumonisins and Fusarium verticillioides. Mycotoxins (Japan), 55:91-100. Wang, R., Dashwood, W.M., Bailey, G.S., Williams, D.E., and Dashwood, R.H. (2006) Tumors from rats given 1,2-dimethylhydrazine plus chlorophyllin or indole-3-carbinol contain transcriptional changes in b-catenin that are independent of b-catenin mutation status. Mutation Res. (in press) Watterson, T.L., Sorenson, J., Martin, R., and R.A. Coulombe, Jr. (200X). Effects of PM2.5 Collected from Cache Valley Utah on Genes Associated with the Inflammatory Response in Human Lung Cells. Toxicology and Applied Pharmacology. (submitted). Williams, L.D., Glenn, A.E., Bacon, C.W., Smith, M.A.and Riley, R.T. (2006) Fumonisin production and bioavailability to maize seedlings grown from seeds inoculated with Fusarium verticillioides and grown in natural soils. Journal of Agricultural and Food Chemistry. 54: 5694-5700. Xiao S, Anderson SP, Swanson C, Bahnemann R, Voss KA, Stauber AJ, Corten JC. (2006) Activation of peroxisome proliferator activated receptor ± (PPAR ±) enhances apoptosis in mouse liver. Toxicological Science 92: 368-377. Xue L, Li M, Pestka JJ, Firestone GL, Bjeldanes LF. (200X) 3,3-Diindolylmethane is a novel immunomodulator that activates cytokine production, lymphocyte proliferation, and reovirus clearance. J Nutrition [submitted] Yip, S.S.M. and R.A. Coulombe, Jr. (2006) Molecular cloning and expression of a novel cytochrome P450 from turkey liver with aflatoxin B1 metabolizing activity. Chemical Research in Toxicology 19:30-37. Yu, Z., Loehr, C., Fischer, K., Louderback, M., Kreuger, S., Dashwood, R., Kerkvliet, N., Pereira, C., Jennings-Jee, J., Dance, S., Miller, M., Bailey, G. and Williams, D. (2006). In utero exposure of mice to dibenzo(a,l)pyrene produces lymphomas in the offspring: Role of the aryl hydrocarbon receptor. Cancer Res. 66:755-762. Zhou, H. R., Islam, Z., and Pestka, J. J. (2005). Induction of competing apoptotic and survival signaling pathways in the macrophage by the ribotoxic trichothecene deoxynivalenol. Toxicol. Sci. 87(1), 113-122. Zhou, H. R., Jia, Q., and Pestka, J. J. (2005). Ribotoxic stress response to the trichothecene deoxynivalenol in the macrophage involves the SRC family kinase Hck. Toxicol. Sci. 85(2), 916-926.