SAES-422 Multistate Research Activity Accomplishments Report

Status: Approved

Basic Information

Participants

Administrative Advisor Michael Harrington (Colorado State), committee members George Bailey (Oregon), Len Bjeldanes (UCBerkeley), Roger Coulombe (Utah), Mendel Friedman (USDA-WRRC Albany, CA), Bill Helferich (Illinois), Bernadene Magnuson (Maryland), Jim Pestka (Micigan State), Ron Riley (USDA-ARS Athens, GA), Frank Stermitz (Colorado State), and Carl Winter (UCDavis).

Accomplishments

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. Chlorophyll and the synthetic derivative chlorophyllin were shown to have cancer protective properties which are related to inhibition of the environmental carcinogens dibenzopyrene and aflatoxin. Chlorophyll and chlorophyllin reduce access of the carcinogens to the liver, but complexation with the carcinogengs is not necessary for this activity. (Oregon). Tomatine, an alkaloid present in tomatoes, was shown to be nontoxic at high levels in a model using trout and hence the model will be useful for long-term studies to determine whether or not it can cause tumor formation or progression. (Oregon; USDA Albany, California). Dietary butylated hydroxytoluene (BHT) protects turkeys against aflatoxicosis caused by aflatoxins. This was shown to be due to inhibition of a consumed aflatoxin to its more toxic epoxide form (Utah State). Extracts of pigmented rice brans were found to be much stronger inhibitors of tumor promotion in marmoset cells than was an extract from nonpigmented white rice cooking varieties (USDA Albany). Green tea catechins, particularly epicatechin gallate, were shown to have potent antibactericidal activity against Bacillus cereus, a close model for Bacillus anthraxis (USDAAlbany). Anthocyanin-rich extracts of bilberry, grape and chokeberry significantly inhibited the growth of human colon cancer cell lines in vitro and also reduced aberrant crypt foci (presumed cancer precursors) in rats (Maryland). Omega-3 fatty acids found in fish oil were effective at suppressing an experimental model of a common kidney disease nephropathy (Michigan State). OBJECTIVE 2. Determine cellular effects and molecular mechanisms of natural and induced toxicants in food for human risk assessment and disease prevention. Gene chips were developed to study the way the indole-3-carbinol dimer (DIM) acts as a tumor promoter in the trout model. The promotion was found to act through an estrogenic pathway and continued after stopping DIM treatment, thus indicating no requirement for chronic exposure. (Oregon) On the other hand, DIM proved to have immune activating and antiangiogenic activity which reduced some tumors in other animal models.(UCBerkeley) These results from two different laboratories emphasize the complex biological interactions which need to be considered with dietary supplements such as DIM. The sensitivity of human white blood cells to the mycotoxin deoxynivalenol (DON or vomitoxin) was found to correlate to presence of a 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 (Michigan State). OBJECTIVE 3. Detect and identify new natural or induced bioactive compounds in foods that have beneficial or adverse effects on human health. Analytical methods were developed 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 toxiicty.(USDA-ARS Georgia). Curcumin, the yellow-coloring pigment in turmeric, was found to inhibit biofilm formation and toxin production in Pseudomonas aeruginosa, which causes lung disease symptoms in cystic fibrosis. This is 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. OBJECTIVE 4. Ascertain how agricultural production an food processing may influence production/stability of natural bioactive chemicals. A survey of literature reports which attempted to compare the beneficial (detrimental) effects of organic vs. traditional agriculture in regard to human health was made. From a scientific viewpoint, few or none of the studies appeared to be conclusive and there was a significant lack of quantitative data which appropriately compared the different methods. (UCDavis). A comparison was made between 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 (Illinois). Maize products utilized in a Guatamalen Central Highland community were analyzed for toxic fumonisns and were often found to exceed 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 fumonosin content than that grown locally. A mouse model for fumonisin risk assessment was developed (USDA Athens, Georgia). COLLABORATIVE PLANS FOR COMING YEAR Bjeldanes(UCBerkeley) and Bailey(Oregon) will continue to study DIM and its carcinogenic and anticarcinogenic properties. Bailey(Oregon) and Friedman(USDA-WRRC Albany) will study the possible antitumour effects of the tomato alkaloid tomatine. Pestka (Michigan State) and Coulombe (Utah) plan to determine immunotoxic endpoints in poultry exposed to aflatoxin. Magnuson (Maryland) and Vivanco (Utah State) will expand their studies on curcumin.

Impacts

  1. Chlorophyll and its derivative chlorophyllin, the additive BHT, and extracts of berries containing high levels of pigments were all found to exhibit properties which suggest they could play an important part as anticarcinogens. Green tea catechins may be useful for combatting anthrax-related infections and omega-3-fatty acids are effective in supressing a common kidney disease.
  2. Lung infections from Pseudomonas aeruginosa are the source of debilitating lung infections in cystic fibrosis and the turmeric component curcumin is used in some case to ameliorate this effect. It was found that curcumin is an effective antiinfective against P. pseudomonas because it inhibits that bacterium from producing its toxins, even though the bacterium is not killed. This is a new way to treat the disease and may not result in bacterial resistanceto drugs.
  3. Refined soy products were found to be more estrogenic than were minimally-processed soy products. Women with estrogen-dependent breast cancer who use soy products should therefore use the less processed varieties.

Publications

Haendel, M.A., F.A. Tilton, G.S. Bailey, and R.L. Tanguay (2004). Developmental toxicity of the dithiocarbamate pesticide sodium metam in zebrafish. Toxicol. Sci. 81(2):390-400. Blum, C.A., Xu, M., Orner, G.A., Diaz, G.D., Li, Q., Dashwood, W.M., Bailey, G.S. and Dashwood, R.H. (2003) Promotion versus suppression of rat colon carcinogenesis by chlorophyllin and chlorophyll: Modulation of apoptosis, cell proliferation, and B-catenin/Tcf signaling. Mutat. Res. 523-524:217-223. Zhang, J., Hsu, J.C., Kinseth, M.A., Bjeldanes, L.F. and Firestone, G.L. Indole-3-carbinol induces a G1 cell cycle arrest and inhibits prostate-specific antigen production in human LNCaP prostate carcinoma cells. Cancer 98: 2511-2520, 2003. Chatterji, U., Riby, J.E., Taniguchi, T., Bjeldanes, E.L., Bjeldanes, L.F.and Firestone, G.L. Indole-3-carbinol stimulates transcription of the interferon gamma receptor 1 gene and augments interferon responsiveness in human breast cancer cells. Carcinogenesis. 18: 291 302, 2003. Leong, H., Riby, J., Firestone, G.L. and Bjeldanes, L. F. Potent ligand-independent estrogen receptor activation by 3,3-diindolylmethane is mediated by cross-talk between the PKA and MAPK signaling pathways. J. Mol. Endo. 18: 291-302, 2004. Rieben, W.K., and Coulombe, R.A. (2004). DNA cross-linking by dehydromonocrotaline lacks apparent base sequence preference. Toxicological Sciences 80, 1-7. Coulombe, R.A. (2003) Pyrrolizidine alkaloids in foods. Advances in Food and Nutrition Research (S.L. Taylor, Ed.). Elsevier Science Ltd., Oxford, U.K. Volume 45, pp. 61-99. Coulombe, R.A., Klein, P.J. and J.O. Hall (2003). Butylated hydroxytoluene chemoprotection: Response to Williams. Toxicology and Applied Pharmacology 189:152. Klein, P.J. Van Vleet, T.R., Hall, J.O. and R. A. Coulombe, Jr. (2003). Effect of dietary buylated hydroxytoluene on aflatoxin B1-relevant metabolic enzymes in turkeys. Food and Chemical Toxicology 41:671-678. Klein, P.J., Hall, J.O. and R. A. Coulombe, Jr. (2003). Dietary butulated hydroxytoluene protects against aflatoxicosis in turkeys, in Poisonous Plants and Related Toxins (T. Acamovic, C.S. Stewart and T.W. Pennycott eds.), CAB International, London. pp. 478-483. Coulombe, R.A., and W. K. Rieben (2003). Lack of Base Sequence Preference of Activated Pyrrolizidine Alkaloid Cross-Links with DNA, in Poisonous Plants and Related Toxins, (T. Acamovic, C.S. Stewart and T.W. Pennycott eds.) CAB International, London. pp. 26-31. Brandon, D. L., Bates, A. H., and Fridman, M. Immunoassays of Bowman-Birk and Kunitz soybean inhibitors in infant formula. J. Food Sci. 69, 11-15, 2004. Friedman, M. Applications of the ninhydrin reaction for analysis of amino acids, peptides, and proteins to agricultural and biomedical sciences. J. Agric. Food Chem. 52, 385-406, 2004. Friedman, M. Effects of food processing. In: Encyclopedia of Grain Science, C. Wrigley, H. Corke and C. E. Walker, eds., Elsevier, Oxford, UK, Vol. 2, pp. 328-340, 2004. Friedman, M. Analysis of biologically active compounds in potatoes (Solanum tuberosum), tomatoes (Lycopersicon esculentum), and Jimson weed (Datura stramonium) seeds. J. Chromatography A, 1054/1-3, 141-153 (special issue devoted to food safety). Friedman, M., Buick, R., and Elliott, C. T. Antibacterial activities of naturally occurring compounds against antibiotic-resistant Bacillus cereus vegeative cells and spores, Escherichia coli, and Staphylococcus aureus. J. Food Protection 67, 1774-1778, 2004. Friedman, M., Henika, P. R., Levin, C. E., and Mandrell, R. E. Antibacterial activities of essential oils and their components against Escherichia coli O157:H7 and Salmonella enterica in apple juice. J. Agric. Food Chem. 52, 6042-6048, 2004, 2004. Han, J. S., Kozukue, N., Young, K. S., Lee, K. R., and Friedman, M. Distribution of ascorbic acid in potato tubers and in home-processed and commercial potato foods. J. Agric. Food Chem. 52, 6516-6521, 2004. Kozukue, N., Han, J. S., Lee, K. R., and Friedman, M. Dehydrotomatine content of tomatoes. J. Agric.Food Chem. 52, 2079-2083, 2004. Lee, K. R., Kozukue, N., Han, J. S., Park, J. H., Chang, E. Y., Baek, E. J., Chang, J. S., and Friedman, M. Glycoakaloids and metabolites inhibit the growth of human colon (HT29) and liver (HepG2) cancer cells. J. Agric. Food Chem. 52, 2832-2839, 2004. Cooke, P.S., Naaz, A., Heine, P.A., Zakroczymski, M.A., Saunders, PTK, Taylor, J.A., Eckel, R.H., Jensen, D.R., Helferich, W.G., and Lubahn, D.B. (2003) Effects of estrogen and phytoestrogen signaling throughestrogen receptor ER-_alpha and ER_-beta on adipose tissue in males and females. Progress in Obesity Research: 9, John Libbey and Co., Eastleigh, United Kingdom pp. 458-461. 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. 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): 1559-1567. Ju, Y-H, C.D. Doerge, DR, Allred, K.F., Allred, C.D. and W.G. Helferich (2002) Dietary Genistein Negates the Inhibitory Effect of Tamoxifen on Growth of Estrogen-dependent Human Breast Cancer (MCF-7) In Vivo. Cancer Research 62:2472-2477 Yellayi S., A. Naaz, M.A. Szewczykowski, T. Sato, J.A. Woods, J. Chang, M. Segre, W.G. Helferich, and P.S. Cooke (2002)., The soy phytoestrogen genistein induces thymic and immune abnormalities in mice: a potential human health hazard? Proc. Natl. Acad. Sci. 99:7616-7621. Hilakivi-Clarke L., E. Cho, A. Cabanes, S. DeAssis, S. Olivo, W.G Helferich M.E. Kuoonab, and R.Clarke (2002) Modulation of pregnancy estrogen levels by maternal dietary exposure to soy isolate or n-3 polyunsaturated fatty acid and breast cancer risk among female rat offspring. J. Clinical Cancer Research 8:3601-3610. M. Malik, C. Zhao, N.W. Schoene, M.M. Giusti, M.P. Moyer, B.A. Magnuson. 2003 Anthocyanin-rich extract from Aronia meloncarpa E. induces a cell cycle block in colon cancer but not normal colonic cells. Nutrition and Cancer 46 (2): 186-196. Y. Kwon, M. Malik and B.A. Magnuson. 2004. Inhibition of colonic aberrant crypt foci by curcumin in rats is affected by age. Nutrition and Cancer 48 (1):37-43. M. Malik and B.A. Magnuson, 2004. Rapid method for identification of chemopreventive compounds using multiplex RT-PCR for cyclooxygenase mRNA expression. Cancer Detection and Prevention. 28(4): 277-282. Kinser, S., Q. Jia, M. Li, A. Laughter, P. Cornwell, J. C. Corton, and J. Pestka. 2004. Gene expression profiling in spleens of deoxynivalenol-exposed mice: immediate early genes as primary targets. J. Toxicol. Environ. Health A 67:1423-1441. Pestka, J. J., H. R. Zhou, Y. Moon, and Y. J. Chung. 2004. Cellular and molecular mechanisms for immune modulation by deoxynivalenol and other trichothecenes: unraveling a paradox. Toxicol. Lett. 153:61-73. Jia, Q., Y. Shi, M. B. Bennink, and J. J. Pestka. 2004. Docosahexaenoic acid and eicosapentaenoic acid, but not alpha-linolenic acid, suppress deoxynivalenol-induced experimental IgA nephropathy in mice. J. Nutr. 134:1353-1361. Gregory, L., J. J. Pestka, D. G. Dearborn, and T. G. Rand. 2004. Localization of satratoxin-G in Stachybotrys chartarum spores and spore-impacted mouse lung using immunocytochemistry. Toxicol. Pathol. 32:26-34. Uzarski, R. L. and J. J. Pestka. 2003. Comparative susceptibility of B cells with different lineages to cytotoxicity and apoptosis induction by translational inhibitors. J. Toxicol. Environ. Health A 66:2105-2118. Moon, Y. and J. J. Pestka. 2003. Deoxynivalenol-induced mitogen-activated protein kinase phosphorylation and IL-6 expression in mice suppressed by fish oil. J. Nutr. Biochem. 14:717-726. Chung, Y. J., H. R. Zhou, and J. J. Pestka. 2003. Transcriptional and posttranscriptional roles for p38 mitogen-activated protein kinase in upregulation of TNF-alpha expression by deoxynivalenol (vomitoxin). Toxicol. Appl. Pharmacol. 193:188-201. Uzarski, R. L., Z. Islam, and J. J. Pestka. 2003. Potentiation of trichothecene-induced leukocyte cytotoxicity and apoptosis by TNF-alpha and Fas activation. Chem. Biol. Interact. 146:105-119. Moon, Y., R. Uzarski, and J. J. Pestka. 2003. Relationship of trichothecene structure to COX-2 induction in the macrophage: selective action of type B (8-keto) trichothecenes. J. Toxicol. Environ. Health A 66:1967-1983. Islam, Z. and J. J. Pestka. 2003. Role of IL-1(beta) in endotoxin potentiation of deoxynivalenol-induced corticosterone response and leukocyte apoptosis in mice. Toxicol. Sci. 74:93-102. Zhou, H. R., A. S. Lau, and J. J. Pestka. 2003. Role of double-stranded RNA-activated protein kinase R (PKR) in deoxynivalenol-induced ribotoxic stress response. Toxicol. Sci. 74:335-344. Pestka, J. J. 2003. Deoxynivalenol-induced IgA production and IgA nephropathy-aberrant mucosal immune response with systemic repercussions. Toxicol. Lett. 140-141:287-295. Bais, H.P., Park, S.W., Weir, T.L. Callaway, R.M., and Vivanco, J.M. (2004) How plants communicate using the underground information superhighway. Trends in Plant Science 9:26-32 Veluri, R., Weir, T.L., Bais, H.P., Stermitz, F.R., and Vivanco, J.M. (2004) Phytotoxic and antimicrobial activities of catechin derivatives. Journal of Agricultural and Food Chemistry 52:1077-1082 Bais, H.P., Fall, R, and Vivanco, J.M. (2004) Biocontrol efficiency of Bacillus subtilis (6051) against Pseudomonas syringae (DC3000) in Arabidopsis thaliana roots is facilitated by biofilm formation and surfactin production. Plant Physiology 134: 307-319 Park, S-W., Vepachedu, R., Owens, R.A., and Vivanco, J.M. (2004) The N-glycosidase activity of the ribosome-inactivating protein ME1 targets single-stranded regions of nucleic acids independent of sequence or structural motifs. Journal of Biological Chemistry 279: 34165-34174 Weir, T., Park, S-W., and Vivanco, J.M. (2004) Biochemical and physiological mechanisms mediated by allelochemicals. Current Opinion in Plant Biology 7:472-479 Walker, T.S., Bais, H.P., Déziel E., Schweizer H.P., Rahme L.G., Fall R., and Vivanco, J.M. (2004) Pseudomonas aeruginosa-plant root interactions: pathogenicity, biofilm formation and root exudation. Plant Physiology 134:320-331 Voss KA, Meredith FI, Bacon CW. 2003. Effect of baking and frying on the in vivo toxicity to rats of cornmeal containing fumonisins. Journal of Agricultural and Food Chemistry 51: 5546-51. Palencia, E. Torres, O., Hagler, W., Meredith, F..I., Williams, L. D., and Riley, R.T. 2003. Total fumonisins are reduced in tortillas using the traditional nixtamalization method of Mayan communities. Journal of Nutrition 133:3200-3203 Sharma RP, He Q, Johnson VJ, Voss KA. 2003. Increased expression of CD95-ligand and other apoptotic signaling factors by fumonisin B1, a hepatotoxic mycotoxin, in livers of mice lacking tumor necrosis alpha. Cytokine 24: 226-236. Marasas, W.F.O., Riley, R.T., Hendricks, K.A., Stevens, V.L., Sadler, T.W., Gelineau-van Waes, J., Missmer, S.A., Cabrera Valverde, J., Torres, O.L., Gelderblom, W., Allegood, J., Martínez de Figueroa, A.C., Maddox, J., Miller, J.D., Starr, L., Sullards, M.C., Roman Trigo, A.V., Voss, K.A., Wang, E., Merrill, A.H., Jr. 2004. Fumonisins disrupt sphingolipid metabolism, folate transport and development of neural crest cells in embryo culture and in vivo: A risk factor for human neural tube defects among populations consuming fumonisin-contaminated maize? Journal of Nutrition. 134:711-716. Williams, L.D., Meredith, F.I., and Riley, R.T. 2004. Fumonisin-ortho-Phthalaldehyde derivative is stabilized at low temperature. Journal of Chromatography (B) 806: 311-314. Merrill, A.H., Jr., Wang, E., Liotta, D.C. and Riley, R.T. 2004. Method of altering sphingolipid metabolism and detecting fumonisin ingestion and contamination. US Patent no. 6,720,184 issued 3 April, 2004. Winter, C.K.: Exposure and dose-response modeling for food chemical risk assessment. In: R.H. Schmidt and G.E. Rodrick (eds.), Food Safety Handbook, Wiley-Interscience, Hoboken, NJ, ps. 73-88, 2003. Winter, C.K.: Pesticides and herbicides. Toxicology. In B.L. Caballero, L. Trugo, and P. Finglas (eds), Encyclopedia of Food Sciences and Nutrition, 2nd Edition, Academic Press, San Diego, ps. 4494-4501, 2003. Winter, C.K.: Surveillance for pesticide residues. In Watson, D.H., (ed.), Pesticide, veterinary and other residues in food. Woodhead Publishing, Cambridge, England, ps. 277-293 (2004).
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