SAES-422 Multistate Research Activity Accomplishments Report

Status: Approved

Basic Information

Participants

Administrative Advisor Richard Heimsch (Idaho), 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), Jorge Vivanco (Colorado State), and Carl Winter (UC Davis).

W-1122: Beneficial and Adverse Effects of Natural, Bioactive Dietary Chemicals on Human Health and Food Safety

Annual meeting of the technical committee, October 10-11, 2002 Calistoga, CA

The annual meeting was called to order at 0830 Thursday morning, October 10th. Present were Administrative Advisor Richard Heimsch (Idaho), 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), Jorge Vivanco (Colorado State), and Carl Winter (UC Davis).

Advisor Heimsch reported that our renewal proposal was finally approved after a long process. Now named W-1122, our project is approved for another five years, until September 30, 2007. Annual reports, summaries, and other entries relating to the project are now to be made online through NIMS- the National Information Management System, working through local Agricultural Experiment Stations. NIMS can be accessed at http://www.colostate.edu/Orgs/WAAESD/ under "Multi-State Research." Committee members were reminded that the "impacts" section of their annual reports are an increasingly important validation of our project, as they are scrutinized by various stakeholders.

Heimsch introduced the two new committee members, Assistant Professor Jorge Vivanco of the Department of Horticulture and Landscape Architecture, Colorado State University, and Ron Riley, of the USDA-ARS Mycotoxin Research Laboratory in Athens, GA. The committee welcomed these new members. In that context, committee members discussed further strengthening W-1122 by continuing to recruit new members. Cathy Davis (U. Delaware) and Berna Magnusson (U Maryland) were identified as possible collaborators.

After these initial items, the annual reports were given.

The regular business portion of the meeting commenced Friday morning at 0930. Ron Riley was elected secretary for the 2003 meeting. He will be responsible for taking minutes of the meeting. Other officers for the upcoming year will be Roger Coulombe, Chair, and Jorge Vivanco, Vice Chair. Colorado and Utah were suggested as possible meeting locations. October 9-10 was agreed upon as the meeting dates.

Accomplishments

October 1, 2001 to September 30, 2002

PROJECT: W-1122 Beneficial and Adverse Effects of Natural, Bioactive Dietary Chemicals on Human Health and Food Safety

COOPERATING AGENCIES AND PRINCIPAL LEADERS:

A. Experiment Stations:

California: L. Bjeldanes (UCB) and C. Winter (UCD); Colorado (CSU): J. Vivanco; Idaho (ID): J. Exon; Illinois (IL): W. Helferich; Michigan (MSU): J. Pestka; Oregon (OSU): G. Bailey; Utah (USU): R. Coulombe.

B. Other Cooperating Agencies:

Western Regional Research Center (WRRC), USDA-ARS, Albany: M. Friedman; Richard B. Russell Research Center, USDA-ARS, Athens, GA: R. Riley.

C. Administrative Advisor: R. Heimsch, University of Idaho PROGRESS OF WORK: OBJECTIVE 1: Investigate the cellular and molecular modes of action by which natural bioactive chemicals in food protect against human diseases such as cancer, inflammation and microbial infection.

In an investigation of the mechanism of ligand-independent activation of the estrogen receptor by 3,3‘-diindolymethane (DIM) in Ishikawa and HEC-1B human endometrial cancer-derived cells, it was found that DIM stimulated the activity of an ER-responsive reporter by up to over 40 fold. The DIM stimulatory effect was abolished when cells were co-treated with the estrogen receptor antagonist ICI-182,780, confirming that activation of the estrogen receptor was necessary for the observed effect. DIM activation was also reduced by 75% and 50%, respectively, from co-treatment of the PKA inhibitor H89 or the MAPK inhibitor PD98059. DIM is a mechanistically novel activator of the estrogen receptor that requires PKA-dependent phosphorylation of CREB and AF-2 transcriptional activity. (CA-B)

DIM was also found to exhibit potent antiproliferative and antiandrogenic properties in androgen dependent human prostate cancer cells. DIM inhibited transcription of the endogenous PSA gene and transfected chimeric PSA reporter constructs and also resulted in decreased levels of secreted and intracellular PSA protein expression induced by dihydrotestosterone. Results indicate that DIM is a potent antagonist of androgen function in prostate tumor cells and establish DIM as a unique bifunctionally active hormone disruptor. (CA-B)

Younger rats had significantly greater numbers of aberrant crypt foci than did older rats when the rats were fed vitamin E in the form of d-alpha tocopheryl succinate. (ID)

A study was conducted 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. (IL)

Soy components were fractionated into several fractions from soy flour and isocaloric and isonitrogenous diets containing the different fractions were provided to mice. There was a significant difference in the tumor growth rate when mice consumed whole soy flour, suggesting that there are compounds in soy flour that reduce bioavailability of genestein or that there are other bioactive products in soy that can alter the effect of genestein. (IL)

The two main omega-3 polyunsaturated fatty acids in fish oil, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), were studied to determine their abilities to retard progression of Primary IgA nephropathy (IgAN) in mice induced by the tricothecene mycotoxin deoxynivalenol (DON). DON significantly increased serum IgA, serum IgA immune complexes and kidney mesangial IgA deposition. DHA, EPA, and DHA/EPA treatment significantly attenuated all three immunopathological parameters as compared to control + DON groups and also significantly reduced IgA secretion by spleen cells. (MSU)

It was shown that DON affects expression of multiple genes that may contribute to its immunotoxic effects and this expression profile can be affected by diet containing omega-3 fatty acids. (MSU)

Experiments to assess 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 is a predictive biomarker for eventual reduction of tumor risk in both target organs (stomach and liver). (OSU)

The effects of green and white teas on tumor development in two mouse models of colorectal cancer are being study. Both teas were shown to effectively suppress tumor development and molecular studies provide evidence that this is, at least in part, suppressing beta-catenin expression in normal intestinal mucosa. (OSU)

In collaboration with OSU researchers, a study introducing an efficient AFB1 metabolizing enzyme into plants is underway to potentially increase in situ detoxification of this mycotoxin in the field. 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. (USU)

OBJECTIVE 2: Determine cellular effects and molecular mechanisms of natural and induced toxicants in food for human risk assessment and disease prevention.

A murine macrophage model, using RAW 264.7 cells, was used to study the effects of DON-mediated apoptosis and DON upregulation of TNF-alpha and MIP-2 expression. Results also suggested that DON induces a signalling cascade in the macrophage that results in elevated TNF-alpha and MIP-2 gene expression. (MSU)

The acute effects of DON on human acute cytokine production in peripheral mononuclear blood leukocytes were studied using a blood culture system. IL-6 and IL-8 were significantly induced by DON as was TNF-alpha. (MSU)

The age-related susceptibility of poultry to AFB1 is being studied to potentially explain why younger turkeys are more susceptible to AFB1. 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 efficient activation. (USU)

OBJECTIVE 3: Detect and identify new natural or induced bioactive compounds in foods that have beneficial or adverse effects on human health.

Use of Hypericum perforatum L., commonly known as St. John‘s wort, has increased recently due to the pharmaceutical potential of hypericin found in its leaves. A novel cell culture system for in vitro growth and production of this species was developed. Light and dark conditions, with cell aggregate size, played an important role in growth and hypericin production in cell suspension cultures. (CSU)

A major gene termed Hyp-1 encoding for hypericin biosynthesis was cloned and characterized from Hypericum perforatum L. cell cultures. (CSU)

The allelopathic capability of the noxious weed Centaurea maculosa (spotted knapweed) was studied. It was found that (-)-catechin is a root-secreted phytotoxin that contributes to C. maculosa‘s 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. (CSU)

Potentially bioactive compounds were identified in studies of wild (7 species) and cultivated (2 species) of western 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. (ID)

OBJECTIVE 4: Ascertain how agricultural production and food processing may influence production/stability of natural bioactive chemicals.

Production of fumonisin mycotoxins produced by the fungus Fusarium moniliforme appears to be strongly influenced by growth conditions. The fungicide metalaxyl appears to be a promising candidate for reducing fumonisin levels as cultures of F. moniliforme grown in media containing the fungicide showed normal fungal growth but significantly reduced levels of fumonisins. Maximum toxin production is observed at pH levels below 3. CA-D)

A comprehensive review of the chemical and biological basis of the formation in food and the toxicological effects of acrylamide was developed. (WRRC)

Impacts

  1. The major indole-3-carbinol product, 3,3'-diindolymethane (DIM) is a novel and potent ligand-independent activator of the estrogen receptor in endometrial cancer cells that functions by initiating cross-talk between two kinase pathways and the estrogen receptor. DIM inhibits androgen activity in prostate tumor cells by competitively binding to the androgen receptor and preventing its translocation to the nucleus.
  2. It is possible that compounds present in high abundance in soy and dietary supplements may stimulate growth of estrogen-dependent breast cancer by individuals that consume significant quantities of the dietary isoflavones.
  3. Studies of Hypericum perforatum L., commonly known as St. John's wort, were conducted to develop an in vitro cell culture system for producing the plant and large quantities of its primary pharmacological agent hypericin. Hypericin levels were increased following exposure to jasmonic acid, and a major gene encoding for hypericin biosynthesis was cloned and characterized. These studies may provide researchers access to appropriate quantities of hypericin to allow its pharmacological properties
  4. Traditional studies of the fungicidal activity of metalaxyl on F. moniliforme that investigate fungal survival may have led researchers to conclude that metalaxyl is not particularly effective, but from a food safety perspective, the reduction in fumonisin levels could be highly beneficial.
  5. Fish oil can block DON-induced IgA dysregulation, providing insight into specific mechanisms by which omega-e fatty acids can block IgAN as well as other autoimmune and inflammatory disease processes. From a practical standpoint, the model may help answer questions about which omega-3s are most effective, the optimal dose regimens and omega-3 to omega-6 ratios, as well as the duration and frequency of omega-3s to get maximum benefit in treating overactive IgA responses and, perhaps, ultimately
  6. CHL continues to show promise as a useful agent for prevention of cancer by at least three common classes of known or suspect human carcinogens - AFB1, heterocyclic amines, and polyaromatic hydrocarbons. The utility of natural chlorophylls, however, remains to be established. The mouse studies add to the growing evidence that tea components may be important dietary factors for the reduction of colon cancer risk
  7. Finding chemoprevention strategies in domestic food animals such as poultry will help American agriculture produce a safer product for consumers
  8. Initial efforts to amplify the trout 2K1 CYP and place it in Agrobacterium is the first step in transforming maize shoot cultures with this AFB1-detoxifying enzyme. Developing a transgenic corn that can detoxify its own AFB1 will help agriculture produce a safer food product.

Publications

PUBLICATIONS:

CALIFORNIA Leong, H., Firestone, G.L. and Bjeldanes, L.F. Cytostatic effects of 3,3‘-diindolylmethane in human endometrial cancer cells result from an estrogen receptor-mediated increase in transforming growth factor-alpha expression. Carcinogenesis 22; 1809-1817, 2001.

Staub, R.E., Feng, C., Onisko, B.; Bailey, G., Firestone, G.L. and Bjeldanes, L.F. Fate of Indole-3-carbinol in MCF-7 breast cancer cells, Chem. Res. Toxicol. 15:101-109, 2002.

Hong, C., Firestone, G.L., and Bjeldanes, L.F. 3,3‘-Diindolymethane (DIM) induces a G1 cell cycle arrest and Bcl-2-mediated apoptosis in human breast cancer cells. J. Biolchem. Pharm. Biochem Pharmacol. 63: 1085-1097, 2002.

Hong, C., Kim, Hyeon-A, Firestone, G.L., and Bjeldanes, L.F. 3,3‘-Diindolylmethane (DIM) induces a G1 cell cycle arrest in human breast cancer cells that is accompanied by Sp1-mediated activation of p21 WAFI/CIP1 expression. Carcinogenesis 23: 1297-1305, 2002.

Leong, H., Firestone, G.L., and Bjeldanes, L.F. Potent ligand-independent estrogen receptor activation by 3,3‘-diindolymethane is mediated by cross-talk between the PKA and MAPK signaling pathways. (submitted for publication) 2002.

Winter, C.K. Electronic information resources for food toxicology. Toxicology 173: 89-96, 2002. (includes discussion of natural toxins)

Garcia, E.L., Winter, C.K. Diet and Cancer. In: Cliver, D.O. and H.P. Reimann, eds., Foodborne Diseases, 2nd Edition, Academic Press, New York (in press, November 2002).

COLORADO Bais, H.P., Walker, T.S., Schweizer, H., Vivanco, J.M. Root specific elicitation and antimicrobial activity of rosmarinic acid in hairy root cultures of sweet basil (Ocimum basilicum L.). Plant Physiology & Biochemistry (in press) November, 2002.

Walker, T.S., Bais, H.P., Schweizer, H.P., Fall, R., Vivanco, J.M. Pseudomonas aeruginosa biofilm: a protective mechanism against plant root-derived antibiotics. Proceedings of the National Academy of Sciences. (Submitted)

Park, S-W., Lawrence, C.B., Linden, J.C., Vivanco, J.M. Characterization of a novel ethylene-inducible ribosome-inactivating protein exuded from root cultures of Phytolacca americana. Plant Physiology 130: 164-178, 2002.

Park, S-W., Stevens, N., Vivanco, J.M. Enzymatic specificity of three ribosome-inactivating proteins against fungal ribosomes, and correlation with antifungal activity. Planta (in press), 2002.

Bais, H.P., Loyola-Vargas, V.M., Flores, H.E., Vivanco, J.M. Root-specific metabolism: the biology and biochemistry of underground organs. In Vitro Cell Dev. - PLANT 37: 730-741, 2001.

Vivanco, J.M., Guimaraes, R., Flores, H.E. Underground plant metabolism: the biosynthetic potential of plant roots. In: Plant Roots the Hidden Half. Y. Waisel, A. Eshel, U. Kafkafi, eds., Marcel Dekker Press, new York, pp 1045-1070, 2002.

Bais, H.P., Walker, T.S., McGrew, J.J., Vivanco, J.M. Cell size aggregation and dark conditions influence growth and production of hypericin in cell suspension cultures of Hypericum perforatum L. (St. Johns Wort). In Vitro Cell. Dev.-PLANT 38: 58-65, 2002.

Walker, T.S., Bais, H.P., Vivanco, J.M. Jasmonic acid-induced hypericin production in cell suspension cultures of Hypericum perforatum L. (St. Johns Wort). Phytochemistry 60 (3): 289-293, 2002.

Bais, H.P., Vepachedu, R., Lawrence, C.B., Stermitz, F.R., Vivanco, J.M. Isolation of a gene responsible for formation of the anti-depressive compound hypericin from St. John‘s Wort (Hypericum perforatum L.) reveals a direct and complex mode of chemical synthesis. Submitted to Nature Biotechnology.

Bais, H.P., Walker, T.S., Stermitz, F.R., Hufbauer, R.A., Vivanco, J.M. Enantiomeric dependent phytotoxic and antimicrobial activity of (1)-catechin; a rhizosecreted racemic mixture from Centaurea maculosa (spotted knapweed). Plant Physiology 128: 1173-1179, 2002.

Bais, H.P., Vepachedu, R., Gilroy, S., Vivanco, J.M. A plant invasion process mediated by root allelochemicals: ecological, physiological, signal transduction and genomics evidence. In preparation for Science, 2002.

Bais, H.P., park, S-W, Halligan, D.M., Stermitz, F.R., Vivanco, J.M. Exudation of fluorescent _-carbolines from Oxalis tuberosa L. roots. Phytochemistry (in press).

Morel, C., Stermitz, F.R., Tegos, G., Lewis, K. Submitted to J. Nat. Prod., 2002.

IDAHO Exon, J.H., South, E.H. Effects of sphingomyelin on aberrant colonic crypt foci development, colon crypt cell proliferation and immune function in an aging rat tumor model. Food and Chemical Toxicology (in press), 2002.

ILLINOIS Santell, R.C., Kieu, N. Helferich, W.G. The phytoestrogen genistin inhibits growth of estrogen-independent human breast cancer cell growth in vitro but not in vivo. J. of Nutrition 130;1665-1669, 2000.

Ju, Y.H., Carson, K., Katzenellenbogen, J., Sun, J., Choi, I.H., Katzenellenbogen, B, Helferich, W.G. Estrogenic effects of extracts from cabbage, fermented cabbage, and acidified brussel sprouts on growth of estrogen-dependent (MCF-7) and -independent (MDA 231) human breast cancer cells. J. Agric. Food Chem. 48: 4628-4634, 2000.

Allred, C.D., Allred, K.F., Ju, Y., Virant, S.M., Helferich, W.G. Soy diets containing genistein stimulate growth of estrogen-dependent (MCF-7) tumors in a dose dependent manner. Cancer Research 61;5045-5050, 2001.

Allred, C.D., Ju, Y., Allred, K.F., Chang, J., Helferich, W.G. Dietary genistein stimulates growth of estrogen-dependent breast cancer tumors similar to that observed with dietary genistein. Carcinogenesis, 22: 1667-1673, 2001.

Ju, Y-H, Allred, C.D., Allred, K.F., Karko, K.L., Helferich, W.G. Dose-response study of soy isoflavone, genistein, at physiological concentration range on the growth of estrogen-dependent human breast cancer (MCF-7) tumor implanted in athymic nude mice. Journal of Nutrition, 131 (11)2957-2962, 2001.

Ju, Y-H, Doerge, C.D., Allred, D.R., Allred, K.F., Helferich, W.G. 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, 2002.

Yellayi, S., Naaz, A., Szewczykowski, M.A., Sato, T., Woods, J.A., Chang, J., Segre, M., Helferich, W.G., Cooke, P.S. The soy phytoestrogen genistein induces thymic and immune abnormalities in mice: a potential human health hazard? Proc. Natl. Acad. Sci. 99:7616-7621, 200X.

Hilakivi-Clarke, L., Cho, E., Cabanes, A., DeAssis, S., Olivo, S., Helferich, W.G., Kuoonab, M.E., Clarke, R. 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 (in press), 200X.

Yellayi, S., Zakroczymski, M., Selvaraj, V., Valli, V.E., Ghanta, V., Helferich, W.G., Cooke, P.S. The phytoestrogen genistein suppresses cell-mediated immunity in mice. J. Endocrinology (in press), 2002.

Helferich, W.G., Allred, C.D., Ju, Y-H., Dietary estrogens and anti-estrogens. In: Food Toxicology, W.G. Helferich and C.K. Winter, eds., CRC Press, Boca Rotan, FL. , 2001.

Helferich, W.G. Effect of genistein on growth of human breast cancer cells in vitro and in vivo. In: Phytochemicals: A New Health Paradigm. Edited by Wayne Bidlack, 2000.

MICHIGAN Yang, G-H., Pestka, J. Vomitoxin (deoxynivalenol) -mediated inhibition of nuclear protein binding to NRE-A, an IL-2 promoter negative regulatory element, in EL-4 cells. Toxicology, 172:169-179, 2002.

Wong, S.S., Zhou, H-R., Pestka, J.J. Effects of vomitoxin (deoxynivalenol) on the binding of transcription factors AP-1, NF-kB and NF-IL6 in raw 264.7 macrophage cells. J. Toxicol.Environ. Health. 65:1161-1180, 2002.

Pestka, J.J., Zhou, H-R., Jia, Q., Timmer, A.M. Dietary fish oil suppresses experimental IgA nephropathy in mice. J. Nutrition, 261-269, 2002.

Islam, Z. Moon, Y.S., Zhou, H-R., King, L.E., Fraker, P.J., Pestka, J.J. Endotoxin potentiation of trichothecene-induced lymphocyte apoptosis is mediated by up-regulation of glucocorticoids. Toxicol. Appl. Pharmacol. 180: 43-55, 2002.

Christensen, H.R., Frokiaer, H., Pestka, J.J. Lactobacilli differentially modulate expression of cytokines and maturation surface markers in murine dendritic cells. J. Immunol., 168 (1): 171-178, 2002.

Sugita-Konishi, Y., Pestka, J.J. Differential up-regulation of TNF-alpha, IL-6, and IL-8 production by deoxynivalenol (vomitoxin) and other 8-ketotrichothecenes in a human macrophage model. J. Toxicol. Environ Health A. 64(8): 619-636, 2001.

Zielinski, T.L., Smith, S.A., Pestka, J.J., Gray, J.I., Smith, D.M. ELISA to quantify hexanal-protein adducts in a meat model system. J. Agric. Food Chem. 49(6): 3017-3023, 2001.

Wong, S.S., Schwartz, R.C., Pestka, J.J. Superinduction of TNF-a and IL-6 in macrophages by vomitoxin (deoxynivalenol) modulated by mRNA stabilization. Toxicology 161:139-149, 2001.

Lee, M-G. Yuan, Q-P., Hart, L.P., Pestka, J.J. Enzyme-linked immunosorbent assays of zearalenone using polyclonal monoclonal and recombinant antibodies. In: M. Trucksess and A.E. Pohland (eds.), Mycotoxin Protocols, Methods in Molecular Biology, Vol. 157: 159-170, Human Press, Totowa, NJ., 2001.

Pestka, J.J., Ha, C.L., Warner, R.W., Lee, J.H., Ustunol, Z. Effects of ingestion of yogurts containing Bifidobacterium and Lactobacillus acidophilus on spleen and Peyer‘s patch lymphocyte populations in the mouse. J. Food Prot. 64: 392-395, 2001

Zhou, H-R., Lau, A.S., Pestka, J.J. An essential role of double-stranded RNA-activated protein kinase PDR in vomitoxin-induced apoptosis in raw 264.7 cells. 41st Society of Toxicology Annual Meeting, Nashville, TN, 2002.

Islam, Z., King, L.E., Fraker, P.J., Pestka, J.J. Differential induction of apoptosis in murine lymphoid subpopulations in vivo following co-exposure to lipopolysaccharide and vomitoxin. 41st Society of Toxicology Annual Meeting, Nashville, TN, 2002.

Jia, Q., Pestka, J.J. Dietary fish oil suppresses vomitoxin-induced IgA nephropathy in the mouse. 41st Society of Toxicology Annual Meeting, Nashville, TN, 2002.

Islam, Z., King, L.E., Fraker, P.J., Pestka, J.J. Differential induction of apoptosis in murine lymphoid subpopulations in vivo following co-exposure to lipopolysaccharide and vomitoxin. 41st Society of Toxicology Annual Meeting, Nashville, TN, 2002.

Moon, Y., Pestka, J.J. Relationship of trichothecene structure to Cox-2 induction in the macrophage model. 41st Society of Toxicology Annual Meeting, Nashville, TN, 2002.

Chung, Y., Pestka, J.J. Enhancement of TNF alpha-mRNA stability by deoxynivalenol through the activation of p38 kinase. 41st Society of Toxicology Annual Meeting, Nashville, TN, 2002.

Pestka, J.J., Chung, Y., Jarvis, B.B., Tak, H. Development of antibodies to satratoxins and application to enzyme-linked immunosorbent assay. 41st Society of Toxicology Annual Meeting, Nashville, TN, 2002.

OREGON Egner, P., Bailey, G., Groopman, J., Kensler, T. Chlorphyllin reduces urinary levels of a carcinogen-DNA adduct biomarker in residents of Qidong, People‘s Republic of China in a randomized, double-blind, placebo-controlled trial. Proc. Natl. Acad. Sciences, USA, 98:14601-14606, 2001.

Stoner, G., Casto, B., Ralston, S., Roebuck, B., Pereira, C., Bailey, G. Development of a multi-organ rat model for evaluating chemopreventive agents: efficacy of indole-3-carbinol. Carcinogenesis 23:265-272, 2002.

Loveland, P., Reddy, A., Pereira, C., Field, J., Bailey, G. Application of matrix solid-phase dispersion in the determination of dibenzo (a, 1) pyrene content of experimental animal diets used in a large-scale tumor study. J. Chromatog. A. 932:33-41, 2001.

UTAH Van Vleet, T.R., Bombick, D.W., Coulombe, Jr., R.A. Inhibition of human cytochrome P450 2E1 activity by nicotine, cotinine, and aqueous cigarette tar extract in vitro. Toxicological Sciences 64, 185-19, 2001.

Coulombe, R.A. Antioxidants protect turkeys against toxicity of aflatoxin. NRI Research Highlights, National Research Initiative Competitive Grants Program, United States Department of Agriculture, Cooperative State Research, Education and Extension Service. No. 6, 2001.

Van Vleet, T.R., Klein, P.J., Coulombe, Jr., R.A, Metabolism of aflatoxin B1 by normal human bronchial epithelial cells. J. Toxicology and Environmental Health, Part A, 63:101-116, 2001.

Van Vleet, T.R., Maci, K., Coulombe, Jr., R.A. Comparative aflatoxin B1 activation and cytotoxicity in human bronchial cells expressing human CYPs 1A2 and 3A4. Cancer Research 62, 105-112, 2002.

Van Vleet, T.R., Klein, P.J., Coulombe, Jr., R.A. Metabolism and cytotoxicity of aflaltoxin B1 in cytochrome P-450-expressing human lung cells. J. Toxicology and Environmental Health, Part A 65: 853-67, 2002.

Klein, P.J., Van Vleet, T.R., Hall, J.O., Coulombe, Jr., R.A. Dietary butylated hydroxytoluene protects against aflatoxicosis in turkeys. Toxicology and Applied Pharmacology 182, 11-19, 2002.

Klein, P.J., Van Vleet, T.R., Hall J.O., Coulombe, Jr., R. A. Biochemical factors underlying the age-related sensitivity of turkeys to aflatoxin B1. Comparative Biochemistry and Physiology, 132: 193-201, 2002.

Klein, P.J., Van Vleet, T.R., Hall, J.O., Coulombe, Jr., R.A. Effect of dietary butylated hydroxytoluene on aflatoxin B1-relevant metabolic enzymes in turkeys. Food and Chemical Toxicology (in press), 2002.

Van Vleet, T.R., Coulombe, Jr., R.A. Aflatoxin B1 alters expression of P43 in human lung cells. Toxicological Sciences (in press), 2002.

Klein, P.J., Hall, J.O., Coulombe, Jr., R.A. Dietary butylated hydroxytoluene protects against aflatoxicosis in turkeys, In: T. Acamovic, C.S. Stewart and T.W. Pennycott (eds.) Poisonous Plants and Related Toxins, CAB International, London (in press), 2002.

Coulombe, R.A., Rieben, W.K. Lack of apparent base sequence preference of activated pyrrolizidine alkaloid cross-links with DNA, In: T. Acamovic, C.S. Stewart and T.W. Pennycott (eds.) Poisonous Plants and Related Toxins, CAB International, London (in press), 2002.

WRRC Brandon, D.L., Friedman, M. Immunoassays of soy proteins. J. Agric. Food Chem. 50: 6635-6642, 2002.

Brandon, D.L., Bates, A.H., Binder, R.G., Montague, W.C.,Jr., Whitehand, L.C., Barker, S.A. analysis of fenbendazole residues in bovine milk by ELISA. J. Agric. Food Chem. 50: 5791-5796, 2002.

Friedman, M., Henika, P.R., Mandrell, R.E. Bactericidal activities of plant essential oils and some of their isolated constituents against Escherichia coli, Salmonella enterica, Campylobacter jejuni, and Listeria monocytogenes. J. Food Protection 65: 1545-1560, 2002.

Friedman, M. Tomato glycoalkaloids: role in the plant and in the diet. J. Agric. Food Chem. 50: 5751-5780, 2002.

Friedman, M., Henika, P.R., Mackey, B.E. Effect of feeding solanidine, solasodine and tomatidine to non-pregnant and pregnant mice. Food Chem. Toxicol. (in press), 2002.

Johnsson, L., Baxter, G.A., Crooks, S.R.H., Brandon, D.L., Elliott, C.T.E. Reduction of sample matrix effects-the analysis of benzimidazole residues in serum by immunobiosensor. Food Agric. Immunol. (in press), 2002.

Kozukue, N., Friedman, M. Tomatine, chlorophyll, _-carotene, and lycopene contents in tomatoes during growth and maturation. J. Sci. Food Agric. (in press), 2003.

Mandrell, R.E., Bates, A.H., Brandon, D.L. Monoclonal antibodies against Campylobacter jejuni and Campylobacter coli outer membrane antigens. U.S. Patent No. 6,395,879. 2002.
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