Brief Summary of Minutes of Annual Meeting

Report Information: " Annual Meeting Dates: 10/06/05 to 10/07/05 " Period the Report Covers: 11/2004 to 10/2005 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), Richard Heimsch (Idaho), Jim Pestka (Michigan State), Ron Riley (USDA-ARS Athens, GA), Jorge Vivanco (Colorado State) 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 6-7, 2005 SunRiver, OR The annual meeting was called to order at 0830 Thursday morning, October 6th. Advisor Michael Harrington provided a report on the current status of funding within USDA for FY 2006. He reported that in the President's budget Hatch funds had been proposed to be reduced 50% and then "zeroed out" for FY2007; however, funding was restored by the House and Senate and in some cases slightly increased. Discussion of future budgets included some proposed program cuts but slight increases in extension funding and funding of the NRI. It is envisioned that disbursing of Hatch funds in the future could become more competitive although the manner in which this would be implemented is currently unclear. There was considerable discussion about the development of "core values" intended to maintain and strengthen the existing network of state institutions. Energy policy and its impact on agriculture was also discussed. After these initial items, the annual reports were given. The regular business portion of the meeting commenced Friday morning at 1000. Monterey California was selected as the site for the 2006 meeting and it was agreed that because a new Project Plan Outline was due in January 2007 (with the final project due in July 2007), that the 2006 meeting would meet for an extra day. For 2006, Bill Helferich would serve as Secretary, Ron Riley as Vice President and George Bailey as President. The agreed days were 4, 5 and 6 October. It was also agreed that presentations at the 2006 meeting would be limited to 20 min so as to provide more time to develop the new project outline and to discuss the new objectives developed by the Rewrite Committee. It was also agreed that the Rewrite Committee would be comprised of Roger Coulombe (Chair), Jim Pestka (to collate information), Len Bjeldanes and a person to be selected from Oregon State University. The Rewrite Committee agreed to meet in August 2006 to develop the Revised Outline and new objectives to be presented at the 2006 meeting of W1122. The meeting was adjourned at around 1200 on 7 October.

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. Two tumor studies compared the cancer chemopreventive efficacy of natural chlorophyll (Chl) with its water soluble food dye derivative chlorophyllin (CHL). Both agents strongly blocked aflatoxin-induced liver and colon cancer in the rat, and dibenzo(a,l)pyrene-induced liver and stomach cancer in the trout.(Oregon). Pathogenic strains of Pseudomonas syringae, but not non-pathogenic strains, were shown to confer host immune defense response by down-regulating secretion of a battery of antimicrobial compounds by the roots of Arabidopsis thaliana. The root tips also cease growing, which is in stark contrast to the belief that plants are sessile organisms that cannot act to avoid contact with pathogens. (Colorado). Exposure to deoxynivalenol (DON), one of the most common trichothecene mycotoxins in cereal grain, induces expression of interleukin-6 (IL-6), a proinflammatory cytokine, in part by triggering binding of the transcription factor cAMP response element binding protein (CREB) to the IL-6 promoter. Mechanism studies indicate that DHA consumption attenuates IL-3 expression by suppressing CREB phosphorylation in the mouse peritoneal macrophage; this occurs by downregulating specific kinase activities but not by upregulating PP1 and PP2A activities. (Michigan State). 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. The turkey liver CYP 1A2 homologue that has AFB1-epoxidation activity was cloned, expressed, and found likely important in the extreme sensitivity of turkeys to aflatoxin B1. (Utah). A new sphingoid base metabolite was identified in renal cells treated with fumonisin B1, and may play an important role in fumonisin renal toxicity. Fumonisin-induced hepatotoxicity in mice was determined by gene expression analyses not to be mediated through peroxisome proliferator responsive pathways. LM/Bc mice were found in reproduction studies to be more sensitive to induction of NTD than CD1, apparently through fumonisin-induced disruption of sphingolipid metabolism in fetal liver in the sensitive strain. (USDA ARS Athens,GA). OBJECTIVE 2: Determine cellular effects and molecular mechanisms of natural and induced toxicants in food for human risk assessment and disease prevention. Gene expression effects of aflatoxin B1 exposure were examined by extracting RNA from tumorous and histologically normal adjacent tissue in rainbow trout liver, and conducting microarray analysis on a salmonid ToxGeneChip. Genes down-regulated at least 2-fold in hepatocellular carcinoma included genes involved in normal liver functioning, blood coagulation and leukocyte aggregation, and iron absorption, whereas up-regulated genes included cell proliferation, extracellular matrix, immunoregulation and acute phase response genes. These expression changes strongly resemble those reported in human and rodent hepatocellular carcinoma. (Oregon). Deoxynivalenol was hypothesized to interfere with the immune response to reovirus infection. Experiments suggested that DON transiently increased both severity of the reovirus infection and shedding in feces as well as elevated reovirus IgA responses. These effects corresponded to suppressed Th1 and enhanced Th2 cytokine expression. (Michigan). The green tea catechins ()-gallocatechin-3-gallate, ()-epigallocatechin-3-gallate, ()-catechin-3-gallate, ()-epicatechin-3-gallate, theaflavin-3, 3-digallate, theaflavin-3-gallate, and theaflavin-3-gallate were found to exhibit antimicrobial activities at nanomolar levels. Freshly prepared tea infusions were more active than day-old teas. Tea catechins without gallate side chains, gallic acid and the alkaloids caffeine and theobromine also present in teas, and herbal (chamomile, peppermint) teas which contain no flavonoids are all inactive (USDA-WRRC Albany, CA). OBJECTIVE 3. Detect and identify new natural or induced bioactive compounds in foods that have beneficial or adverse effects on human health. 3,3'-diindolymethane (DIM) was found to inhibit Ras signaling induced by VEGF and other growth factors, which interferes with its downstream biological effects necessary for angiogenesis. Further studies showed that DIM strongly inhibited DNA topoisomerase IIa in a supercoiled DNA relaxation assay and instantly blocked DNA synthesis and mitosis. These results identified a new mode of action for this intriguing dietary component that is clearly distinct from the mitogenic effects of tumor promoters on these cells. (UC Berkeley). An improved HPLC method was developed and used to quantify capsaicin, dihydrocapsaicin, homocapsaicin-I, homocapsaicin-II, homodihydrocapsaicin-I, homodihydrocapsaicin-II, nonivamide, and nordihydrocapsaicin levels in parts of the pepper fruit (pericarp, placenta, seeds and in the top, middle, and base parts of whole peppers), in 17 species of peppers, and in 23 pepper-containing foods. (USDA-WRRC Albany, CA). OBJECTIVE 4. Ascertain how agricultural production and food processing may influence production/stability of natural bioactive chemicals. Baking cookies and crackers was found not to appreciable destroy DON, but it was degraded or otherwise "lost" during the frying of donuts. Maize samples from highland (> 1700 m) areas in Guatemala were found to be far less contaminated with fumonisin than lowland samples, where NTD incidence is often very high (USDA-ARS Athens, GA). OBJECTIVE 5. Identify and investigate modes of action of food-borne factors which may reduce the impact of dietary carcinogens. A preclinical mouse model was used to show that the soy phytochemical genestein acts in an additive manner with estrogen to stimulate growth of MCF-7 tumor growth in athymic mice. Daidzein was less effective, and its bacterial metabolite equal was ineffective in this model. (Illinois). The potato glycoalkaloids a-chaconine and a-solanine were purified and evaluated in a tetrazolium microculture (MTT) assay to assess anticarcinogenic effects. All samples tested reduced the numbers of the following human cell lines: cervical (HeLa), liver (HepG2), lymphoma (U937), stomach (AGS and KATO III) cancer cells and normal liver (HeLa Chang) cells. The results show that (a) the effects were concentration dependent in the range 0.1 to 10 mg/mL; (b) a-chaconine was more active than was a-solanine; (c) some mixtures exhibited synergistic effects; (d) the different cancer cells varied in their susceptibilities to destruction; and (e) the destruction of normal liver cells was lower than that of cancer liver cells.

Park S-W, Prithiviraj B, Vepachedu R and Vivanco JM 2005. Isolation and purification of ribosome-inactivating proteins. In Plant Tissue Culture Protocols. V. M. Loyola-Vargas and F. A. Vázquez-Flota, eds. Humana Press, Totowa, New Jersey, 335  347 Prithiviraj B, Bais HP, Weir T, Suresh B, Najarro EH, Dayakar BV, Schweizer HP, and Vivanco JM 2005. Salicylic acid down regulates virulence factors of Pseudomonas aeruginosa thereby attenuating its virulence on Arabidopsis thaliana and Caenorhabiditis elegans. Infection and Immunity 73:5319-5328 Horiuchi J, Prithiviraj P, Bais H.P, Kimball BA, and Vivanco JM 2005. Soil nematodes mediate positive interactions between legume plants and rhizobium bacteria. Planta DOI: 10.1007/s00425-005-0025-y Hompesch RW, Garcia CD, Weiss DJ, Vivanco JM, and Henry CS 2005. Analysis of natural flavonoids by microchip-micellar electrokinetic chromatography with pulsed amperometric detection. The Analyst 130:694-700. Callaway RM, Ridenour WM, Laboski T, Weir T, and Vivanco JM 2005. Natural selection for resistance to the allelopathic effects of invasive plants. Journal of Ecology 93:576-583 Prithiviraj B, Bais HP, Jha AK, and Vivanco JM 2005. Staphylococcus aureus pathogenicity on Arabidopsis thaliana is mediated either by a direct effect of salicylic acid on the pathogen or by SA-dependent, NPR1 independent host responses. Plant Journal 42:417-432 Bais HP, Prithiviraj B, Jha AK, Ausubel FM, and Vivanco JM 2005. Root exudation of antimicrobials mediates pathogen resistance. Nature 434:217-221 Vepachedu R, Park S-W, Sharma N, and Vivanco JM 2005. Bacterial expression and enzymatic activity analysis of ME1, a ribosome-inactivating protein from Mirabilis expansa. Protein Expression and Purification 40:142-151 Vivanco JM, Cosio E, Loyola-Vargas VM, and Flores HE 2005. Los mecanismos quimicos de defensa en las plantas. Investigación y Ciencia [Scientific American Latinoamerica] 341:68-75 Prithiviraj B, Weir T, Bais HP, Schweizer HP and Vivanco JM 2005. Plant models for animal pathogenesis. Cellular Microbiology 7:315-324 Thelen GC, Vivanco JM, Newingham B, Good W, Bais HP, Landres P, Caesar A and Callaway RM 2005. Insect herbivory stimulates allelopathic exudation by an invasive plant and the suppression of natives. Ecology Letters 8:209-217 Jha AK, Bais HP and Vivanco JM 2005. Enterococcus faecalis uses mammalian virulence-related factors to exhibit potent pathogenicity in the Arabidopsis thaliana plant model. Infection and Immunity 73:464-475 Friedman M and Mottram DS (Editors) 2005. Chemistry and Safety of Acrylamide in Food, Springer, New York; Advances in Experimental Medicine and Biology, Volume 561 Friedman M 2005. Biological effects of Maillard browning products in relation to safety of acrylamide. Advances in Experimental Medicine and Biology 561, 135-156 Friedman M, Lee K R, Kim HJ, Lee IS and Kozukue N 2005. Anticarcinogenic effects of glycoakaloids from potatoes against human cervical, liver, lymphoma, and stomach cancer cells. Journal of Agricultural and Food Chemistry 53, 6162-6169 Nam SH, Choi SP, Kang MY, Kozukue N and Friedman M 2005. Antioxidative, antimutagenic, and anticarcinogenic activities of rice bran extracts in chemical and cell assays. Journal of Agricultural and Food Chemistry 53, 816-822 Nam SH, Choi SP, Kang MY, Koh H J, Kozukue N and Friedman M 2005. Bran extracts from pigmented rice seeds inhibit tumor promotion in lymphoblastoid B cells by phorbol ester. Food and Chemical Toxicology 43, 741-745 Cousin MA, Riley RT and Pestka JJ 2005. Foodborne mycotoxins: Chemistry, biology, ecology, and toxicology. in "Foodborne Pathogens: Microbiology and Molecular Biology". Pp 164-226. P. M. Fratamico and A. K. Bhunia (ed) Horizon Scientific Press, Ltd., Norfolk, UK. Riley RT and Pestka J 2005. Mycotoxins: metabolism, mechanisms and biochemical markers. In "The Mycotoxin Blue Book" Duarte Diaz, Ed., pp 279-294. Nottingham University Press, Nottingham, UK. Rentz SS, Meredith FI, Showker JA and Riley RT 2005. Inhibition of Sphingolipid Biosynthesis Decreases Phosphorylated ERK2 in LLC-PK1 Cells. Food and Chemical Toxicology. 43: 123-131 He Q, Riley RT, and Sharma RP 2005. Myriocin prevents fumonisin B1-induced sphingoid base accumulation in mice liver without ameliorating hepatotoxicity. Food and Chemical Toxicology 43:969-979 Gelineau-van Waes J, Starr L, Maddox JR, Aleman F, Voss KA, Wilberding J and Riley RT 2005. Maternal fumonisin exposure and risk for neural tube defects: Disruption of sphingolipid metabolism and folate transport in an in vivo mouse model. Birth Defects Research (A) 73: 487-497 Piva A, Casadei G, Pagliuca G, Cabassi E, Galvano F, Solfrizzo M, Riley RT and Diaz DE 2005. Inability of activated carbon to prevent the toxicity of culture material containing fumonisin B1 when fed to weaned piglets Journal of Animal Science 83: 1939-1947 Stauber AJ, Brown-Borg H, Liu J, Waalkes MP, Laughter A, Staben RA, Coley JC, Swanson C, Voss KA, Kopchick JJ and Corton JC 2005. Constitutive expression of peroxisome proliferator-activated receptor alpha-regulated genes in dwarf mice. Molecular Pharmacology. 67: 681-694 Humpf H-U and Voss KA 2004. Effects of food processing on the chemical structure and toxicity of fumonisin mycotoxins.Molecular Nutrition and Food Research 48:255-269 Corton JC, Apte U, Anderson SP, Limaye P, Yoon L, Latendresse J, Dunn C, Everitt JI, Voss KA, Swanson C, Kimbrough C, Wong JS, Gill SS, Chandraratna RA, Kwak M, Kensler TW, Stulnig TM, Steffensen KR, Gustafsson JA, Mehendale HM. 2004. Mimetics of caloric restriction include agonists of lipid-activated nuclear receptors. Journal of Biological Chemistry 279: 46204-46212 Voss KA, Riley RT, and Gelineau-van Waes J 2005. Trends in fumonisin research: Recent studies on the developmental effects of fumonisins and Fusarium verticillioides. Mycotoxins 55: 91-100 Dalessandri KM, Firestone GL, Fitch MD, Bradlow HL and Bjeldanes LF 2004. Pilot study: effect of 3,3'-diindolylmethane (DIM) supplements on urinary hormone metabolites in postmenopausal women with a history of early stage breast cancer. Nutrition and Cancer 50(2): 161-167 Chang X, Tou JC, Hong C, Kim H-A, Riby J, Firestone GL and Bjeldanes LF 2005. 3,3-Diindolylmethane inhibits angiogenesis and the growth of transplantable human breast carcinoma in athymic mice. Carcinogenesis 26(4): 771-778 Garcia HH, Brar GA, Nguyen DHH, Bjeldanes LF and Firestone GL 2005. Indole-3-carbinol (I3C) inhibits cyclin dependent kinase-2 function in human breast cancer cells by regulating the size distribution, associated cyclin E forms and subcellular localization of the CDK2 protein complex. J. Biol. Chem. 280(10): 8756-64 Xue L, Schaldach CM, Janosik T, Bergman J, and Bjeldanes LF 2005. Effects of analogs of indole-3-carbinol cyclic trimerization product in human breast cancer cells. Chem. Biol. Interact. 152(2-3): 119-29 Xue L, Firestone GL and Bjeldanes LF 2005. DIM stimulates IFNgamma gene expression in human breast cancer cells via the specific activation of JNK and p38 pathways. Oncogene. 24(14): 2343-53 Hsu JC, Zhang J, Dev A, Wing A, Bjeldanes LF. and Firestone GL 2005. Indole-3-carbinol inhibition of androgen receptor expression and down-regulation of androgen responsiveness in human prostate cancer cells. Carcinogenesis. 2005 Jun 15; [Epub ahead of print] Brew CT, Aronchik I, Hsu JC, Sheen JH, Dickson RB, Bjeldanes LF and Firestone GL 2005. 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. 2005 Sep 8; [Epub ahead of print] Coulombe RA, Guarisco JA, Klein PJ and Hall JO 2005. Chemoprevention of aflatoxicosis in poultry by dietary butylated hydroxytoluene. Animal Feed Science and Technology 121: 217-225 Yip SSM and Coulombe RA Jr. 2005. Molecular cloning and expression of a novel cytochrome P450 from turkey liver with aflatoxin B1 metabolizing activity. Chem. Res. Toxicol. (submitted for publication) Van Vleet TR, Watterson TL, Klein PJ and Coulombe RA, Jr. 2005. Aflatoxin B1 alters the expression of p53 in cytochrome P450-expressing human lung cells. Toxicological Sciences. (in press) Rieben WK and Coulombe RA 2004. DNA cross-linking by dehydromonocrotaline lacks apparent base sequence preference. Toxicological Sciences 82, 497-503 Islam Z and Pestka JJ 2005. LPS priming potentiates and prolongs proinflammatory cytokine response to the trichothecene deoxynivalenol in the mouse. Toxicol. Appl. Pharmacol. (in press) Smolinski AT and Pestka JJ 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 Zhou HR, Islam Z and Pestka JJ 2005. Induction of competing apoptotic and survival signaling pathways in the macrophage by the ribotoxic trichothecene deoxynivalenol. Toxicol. Sci. 87(1), 113-122 Li M, Cuff CF and Pestka J 2005. Modulation of murine host response to enteric reovirus infection by the trichothecene deoxynivalenol. Toxicol. Sci. 87(1), 134-145 Urraca JL, ito-Pena E, Perez-Conde C, Moreno-Bondi MC and Pestka JJ 2005. Analysis of zearalenone in cereal and Swine feed samples using an automated flow-through immunosensor. J Agric. Food Chem. 53(9), 3338-3344 Jia Q and Pestka JJ 2005. Role of cyclooxygenase-2 in deoxynivalenol-induced immunoglobulin a nephropathy. Food Chem. Toxicol. 43(5), 721-728 Zhou HR, Jia Q and Pestka JJ 2005. Ribotoxic stress response to the trichothecene deoxynivalenol in the macrophage involves the SRC family kinase Hck. Toxicol. Sci. 85(2), 916-926 Pestka JJ and Smolinski AT 2005. Deoxynivalenol: toxicology and potential effects on humans. J Toxicol. Environ. Health B Crit Rev. 8(1), 39-69 Kinser S, Li M, Jia Q and Pestka JJ 2005. Truncated deoxynivalenol-induced splenic immediate early gene response in mice consuming (n-3) polyunsaturated fatty acids. J Nutr. Biochem. 16(2), 88-95 Pestka JJ, Uzarski RL 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 Allred CA, Allred KF, Ju YH, Doerge DR, Schantz S, Korol D and Helferich WG 2004. Dietary genistein results in larger MNU-induced, estrogen-dependent mammary tumors following ovariectomy of Sprague-Dawley rats. Carcinogenesis 25:211-218 Muthyala RS, Ju YH, Sheng S, Williams LD, Doerge DR, Katzenellenbogen BS, Helferich WG and Katzenellenbogen JA 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): 1559-1567 Selvaraj V, Zakroczymski MA, Naaz A, Mukai M, Ju YH, Doerge DR, Katzenellenbogen JA, Helferich WG and Cooke PS 2004. Estrogenicity of the isoflavone metabolite equol on reproductive and non-reproductive organs in mice. Biology of Reproduction 71:966-972 Ju YH, Clausen LM, Almada AL and Helferich WG 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) Allred CA, Allred KF, Ju YH, Doerge DR and Helferich WG 2004. Soy processing influences growth of estrogen-dependent breast cancer tumors. Carcinogenesis 25(9):1649-1657 Allred CD, Twaddle NC, Allred KF, Churchwell MI, Ju YH, Helferich WG and Doerge DR 200X. Soy processing affects metabolism and disposition of dietary isoflavones in ovariectomized Balb/c mice. J. Ag and Food Chem. (In Press) Ju YH, Fultz J, Allred KF, Doerge DR and Helferich WG 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.Carcinogenesis(In Press) Tilton SC, Givan SA, Pereira C, Bailey GS and Williams DE 2005. Toxicogenomic profiling of the hepatic tumor promoters indole-3-carbinol, 17²-estradiol and ²-naphthoflavone in rainbow trout. Toxicol. Sci. Advanced Access Sept. 28, 2005. 10.1093/toxsci/kfi341 Tilton SC, Gerwick, LG, Hendricks JD, Rosato C, Corley-Smith G, Givan SA, Bailey GS, Bayne CJ and Williams DE 2005. Use of a rainbow trout oligonucleotide microarray to examine transcriptional patterns in aflatoxin B1-induced hepatocellular carcinoma compared to adjacent liver. Toxicol. Sci. Advanced Access Sept. 1, 2005. 10.1093/toxsci/kfi309