Brief Summary of Minutes of Annual Meeting

Annual meeting of the technical committee, October 4-5, 2007 Calistoga, CA

The annual meeting was called to order at 0800 Thursday morning, October 4th.

Advisor Michael Harrington provided a report on the current status of USDA funding and new initiatives within USDA for FY 2008. He reported that funding for food safety and the National Research Initiative were in good shape in the proposed 2008 budget. He also discussed possible funding for the W2122 group's collaborative research through the CSREES "National Integrated Food Safety Initiative" which will emphasize multidisciplinary teams from multiple states and/or institutions.

After these initial items, the annual reports were given.

The regular business portion of the meeting commenced Friday morning at 0830. Hawaii was selected as the site for the 2008 meeting and it was agreed that the 2008 meeting would meet Thursday and Friday the 2nd week in October. The agreed days were Thursday and Friday the 9th and 10th of October with arrival on Wednesday 8 October. For 2008, Pratiba Nerurkar (University of Hawaii) would serve as Secretary, Mike Denison (University of California, Davis as Chair-elect, and Bill Helferich (University of Illinois) as Chair. The responsibilities of the Secretary, Chair-elect and Chair were discussed and it was agreed that the Chair writes the report and chairs the meeting, the Chair-elect organizes the next years meeting working closely with the local host and also assists the Chair in writing the report, the Secretary writes the minutes. Submission of the Report and the minutes are the responsibility of the Chair and the Secretary. The meeting was adjourned at around 1200 on 7 October.

OBJECTIVE 1. Consumption of food-borne bioactive compounds can protect against human diseases such as cancer, inflammation, birth defects, and microbial infection. We will determine the mechanisms by which selected compounds exert their protective action. A high affinity CYP1A5 was cloned from turkey liver with high AFBO formation activity. Subsequently a CYP3A4 homologue, CYP3A37 (Genbank DQ450083) was amplified and cloned with 76% sequence identity to human 3A4 and 97% identity to chicken CYP3A37. A truncated construct of the turkey CYP3A37 gene was expressed in Escherichia coli competent cells. The expressed protein metabolized AFB1 to form two metabolites. Comparing the kinetic parameters with those previously reported for CYP1A5, it appears that CYP3A37 has greater activity toward AFB1 epoxidation. Two GST enzymes were also cloned from turkeys. A study with dietary BHT showed that in turkeys fed BHT plus AFB1 that the BHT-fed turkeys had significantly less aflatoxin B1 in tissues and that the BHT levels in the tissues were substantially below U.S. FDA guidelines (Utah State University). Studies are ongoing to identify and characterize natural products or derivatives of natural products with therapeutic applications whose mechanisms of action are mediated via intracellular ligand-dependent nuclear receptor signaling systems (University of California, Davis). The emphasis has been on chemicals that specifically interact with and affect the function of the estrogen receptor (ER) and the aryl hydrocarbon receptor (AhR); specifically, analysis of natural and synthetic flavonoids for their ability to activate the AhR and ER signaling pathways using our recombinant cell lines. Several compounds were identified that appear to be relatively potent/efficacious activators of the ER, the bulk of the compounds were inactive. Interestingly, a large number of these chemicals could activate/inhibit the AhR signal tranduction pathway. We have also examined the ability of a number of these chemicals to inhibit proliferation of human liver (HepG2) cells or breast cancer (T47D) cells and have found that those chemicals that are agonists of the AhR could inhibit cell proliferation. Several of these chemicals will be examined for their functional chemotherapeutic activity in mice in vivo and in cancer cell systems in collaboration with Bill Helferich (University of IL) and Len Bjeldanes (University of California, Berkeley). We have begun a collaboration with Dr. Coulombe at UT to examine the functional activity of the AhR in turkey hepatic cytosolic samples we have obtained. Consumption of the n-3 polyunsaturated fat docosahexaenoic acid (DHA) was found to modulate the mucosal immune response to enteric infection with reovirus, a model intestinal pathogen. Mice were fed with either control diet or diet high in DHA-enriched fish oil for 4 wk and then gavaged with reovirus. Reovirus-specific IgA antibody was first detectable in the feces of mice fed control diet at 6 d post infection (PI) and was further elevated at 8 and 10 d. IgA responses in DHA-fed mice were similar at 6 and 8 d PI but greater at 10 d PI. Both reovirus-specific serum IgA and IgG2a were comparably induced in mice fed control or DHA diets. While both groups carried similar numbers of reovirus plaque-forming units (PFU) per intestine, DHA-fed mice shed nearly 10 times more viral RNA than control mice in feces at 2, 4, and 6 d PI. However, viral RNA was not detectable in either group at 8 and 10 d. Taken together, these data suggest that DHA consumption did not markedly alter mucosal or systemic immunoglobulin responses to reovirus and only slightly delayed clearance of the virus from the gastrointestinal tract (Michigan State University). Bitter melon (BM) is widely cultivated in Asia, East-Africa and South America and extensively used in folk medicines as a remedy for diabetes and its complications. We have recently demonstrated that BM juice (BMJ) reduces weight gain in mice fed a high-fat-diet (HFD) containing 58% fat. In our studies, BMJ also improved diabetes (fasting glucose and glucose and insulin tolerance) in these mice fed HFD as well as reduced triglycerides and the bad cholesterol (very low density lipoproteins, VLDL; low density lipoproteins, LDL) in the liver and blood of these HFD-fed mice. We further demonstrated that reduction in apolipoprotein B (apoB) was possibly due to BMs insulin-mimetic mechanisms through phosphorylation of insulin receptor and its down-stream targets (University of Hawaii). OBJECTIVE 2. Food-borne toxins and carcinogens are present per se or are induced by processing, preparation, and other post-harvest steps. We will identify mechanisms of action and develop biomarkers of natural and induced toxicants in food for human risk assessment and disease prevention. Little is known regarding the pharmacokinetics of AFB1 uptake, distribution, and elimination in humans. To examine chlorophyll chemopreventive mechanisms in humans, we have used IRB approved ultra-low dose 14C-AFB1 to assess these parameters in human volunteers. AFB1 was given on an empty stomach by capsule, and serum and urine samples were collected over 72 hours and sent to Lawrence Livermore for 14C determination by accelerator mass spectrometry. Although statistical analysis is not completed, the data provide convincing evidence that both CHL and Chl can significantly lower urinary excretion of aflatoxins in one or more volunteers, and alter plasma pharmacokinetic parameters for AFB1 uptake and disposition. These results provide the most complete pharmacokinetic analysis ever conducted for AFB1 in humans, and the first evidence that natural chlorophyll can reduce systemic uptake of AFB1 from the GI tract in humans (Oregon State University). Avlimil, a dietary supplement containing 11 different botanicals was shown to act as an estrogen or anti-estrogen depending on the dietary dosage. An extract of Avlimil was tested for its estrogenic and anti-estrogenic effects on the growth of MCF-7 cells in vitro. We observed in vitro that the DMSO extract of Avlimil (0.1-50 mg/mL media) increased MCF-7 cell proliferation, and Avlimil DMSO extract (at 100 mg/mL) inhibited proliferation in a dose-dependent manner. Avlimil and some constituents (black cohosh root and licorice root supplements) were fractionated by using sequential solvent extraction (hexane, ethyl acetate, and methanol) and the activity of the fractions were monitored by effects on the growth of MCF-7 cells. Depending on dosage (0.1  100 mg/mL media) both stimulatory and inhibitory effects of the extracts on the growth of MCF-7 cell were observed. The effect of dietary Avlimil at dosages approximating human intake was evaluated using a xenograft model, in which ovariectomized mice implanted with MCF-7 cells were fed diets containing 500 ppm or 1000 ppm Avlimil for 16 weeks. Dietary Avlimil at 500 ppm stimulated MCF-7 tumors, but Avlimil at 1000 ppm had no apparent effect on the growth of MCF-7 tumors, presumably because of combined estrogenic and anti-estrogenic effects. The observation of stimulated tumor growth in the absence of uterine wet weight gains suggest that estrogenic effect of Avlimil we observed may be dosage- and target tissue-specific, and that Avlimil may not be safe for women with estrogen-dependent breast cancer. The different biological effects of Avlimil extracts and different concentration dependencies warrant further dose-response studies, especially at lower dietary concentrations to determine dosages that have estrogenic effects (University of Illinois). The effects of deoxynivalenol (DON) on Bip (glucose-regulated protein [GRP]-78) and related signaling pathways were examined in the macrophage. Bip protein expression was markedly decreased in mouse peritoneal macrophages following incubation with DON (500 ng/ml) for 1 h and was almost completely undetectable from 6 to 24 h. Incubation with DON was found to markedly increase inositol-requiring enzyme -1, X-box-binding protein -1 and the unfolded protein response (UPR) sensor (ATF-6) protein expression within 1 h. Pretreatment of macrophages with an inhibitor of double-stranded RNA activated protein kinase (PKR) blocked expression of both IRE1 and IL-6. These data suggest that DON-induced IL-6 expression is PKR-dependent and might be mediated by Bip degradation and an ensuing UPR (Michigan State University). The capacities of ricin and DON to cleave 28S ribosomal RNA (rRNA) were compared. In a cell-free model, exposure to ricin at 320 ng/ml for 30 min depurinated yeast 28S rRNA. In contrast, DON at < 4000 ng/ml did not directly depurinate yeast 28S rRNA after 1 h incubation. Incubation of RAW 264.7 macrophages with either 20 to 320ng/ml of ricin or 250 to 5000 ng/ml of DON for 6 h generated 28S rRNA-specific products consistent with cleavage sites 1.2 and 1.5 kilonucleotide (knt) from the 3 terminal end of mouse 28S rRNA. When ricin-treated RAW 264.7 cells were analyzed by primer extension, two cleavage sites were identified, one (A4325) at the ricin/sarcin loop, and another (C4037) at the center of the peptidyl transferase. Although similar DON exposure did not damage the ricin/sarcin loop, the treatment caused cleavage of 28S rRNA at two sites (C4037 and A3560) in the peptidyl transferase center, where anisomycin is known to act, and at a third site (G3656). RNase activity as well as RNase 6 and RNase L mRNAs were increased in RAW 264.7 cells that were incubated with ricin (> 20 ng/ml) or DON (>125 ng/ml). These data suggest that ricin cleaves 28S rRNA directly and indirectly via RNase induction whereas DON induces 28S rRNA cleavage only by indirect induction of RNases (Michigan State University). A study in collaboration with Janee Gelineau van Waes (University of Nebraska) was undertaken to see if sphinganine 1-phosphate and its synthetic analog FTY 1-phosphate were elevated in blood, plasma and other tissues of SWV and LMBc mice treated with FB (ip injection) or FTY (gavage). The results show that in FB treated mice the levels of sphingoid bases and sphingoid base 1-phosphates are significantly elevated in blood, plasma and decidua. In the blood and plasma of FB treated mice the amount of Sa and Sa-1P were significantly greater in the LMBc mice as was the NTD incidence compared to the SWV mice. In the FTY treated animals FTY 1-P was significantly elevated in plasma and decidua in both strains although the levels in LMBc mice were greater than in the SWV as was the incidence of NTD. The results suggest that elevation in S1P receptor agonists may be risk factors for NTD (USDA-ARS, Athens). In collaboration with scientists in Guatemala and Duke University approximately 100 maize samples from local markets in highland and lowland Departments in Guatemala were analyzed for fumonisins. The results provide additional strong support for our hypothesis that lowland maize is the major source of exposure to fumonisins (an inhibitor of ceramide synthase and folate transport) in the highlands where NTD incidence is very high (USDA-ARS, Athens). In breast cancer MCF-7 cells the AhR-ligands B[a]P and TCDD stimulated transcription activity of a 3.9 Kb COX-2 promoter fragment and an AhR-responsive construct containing an enhancer element from the CYP1A1 promoter linked to an array of four XREs (pCYP1A1-4XRE). The TCDD-dependent induction of COX-2 transcription is mediated by two XRE sites (XRE-1 and XRE-2) which are targets for binding by the AhR. Both the stimulation by TCDD of COX-2 transcription activity and the binding of the AhR to the two XREs harbored in the 3.9kb COX-2 promoter fragment are repressed by cotreatment with a mixture of isomers of the dietary lipid conjugated linoleic acid (CLA) and selected isomers (t10,c12-CLA>c9,t11-CLA). The binding of the AhR to COX-2 and CYP1A1 oligonucleotides containing a consensus XRE was counteracted by synthetic (3-methoxy-4-naphthoflavone) and natural (resveratrol) AhR antagonists. Thes results show that the AhR directly participates in the trans-activation of the COX-2 promoter and that this mechanism is a potential target for dietary agents in the prophylactic management against stimulation of COX-2 expression by AhR agonists (University of Arizona). OBJECTIVE 3. Selected classes of bioactive compounds show potential for beneficial or adverse effects on human health. We will discover bioactive compounds that have beneficial or adverse effects on human health. The effects of 3,3-diindolymethane (DIM) on hypoxia signaling in cultured tumor cells was examined. It was found that DIM reduces levels of HIF-1a and HIF-1 activity in hypoxic cultured human cancer cells. DIM reduced the level of HIF-1a in hypoxic cells by increasing the rate of the prolyl hydroxylase- and proteosome-mediated degradation of HIF-1a, and by decreasing the rate of HIF-1a transcription. Using enzyme kinetics studies, we established that DIM binds to the oligomycin binding site on the F1 transmembrane component on mitochondrial F1F0-ATPase. The contributions of the resulting increases in levels of ROS and O2 in hypoxic cells to the inhibitory effects of DIM on HIF-1a expression are not fully clear. These studies are the first to show that DIM can decrease the accumulation and activity of the key angiogenesis regulatory factor, HIF-1a, in hypoxic tumor cells (University of California, Berkeley). N-Alkoxy derivatization of indole-3-carbinol (I3C) increases the efficacy of the G1 cell cycle arrest of human MCF-7 breast cancer cells. Structure-activity relationships of I3C that mediate this anti-proliferative response were investigated using synthetic and natural I3C derivatives that contain substitutions at the indole nitrogen. In indole-treated human MCF-7 breast cancer cells, dose response experiments examining the inhibition of DNA synthesis and G1 cell cycle arrest revealed a striking increase in efficacy of the N-alkoxy I3C derivatives that is significantly enhanced by the presence of increasing carbon lengths of the N-alkoxy substituents. Compared to I3C, the half maximal growth arrest responses occurred at 23-fold lower indole concentration for N-methoxy-I3C, 50-fold lower concentration for N-ethoxy-I3C, 217-fold lower concentration for N-propoxy-I3C, and 470-fold lower concentration for N-butoxy-I3C. At these lower concentrations, each of the N-alkoxy substituted compounds induced the characteristic I3C response in that CDK6 gene expression, CDK6 promoter activity, and CDK2 specific enzymatic activity for its retinoblastoma protein substrate were strongly down-regulated. In contrast to these effects, 3-methoxymethylindole and 3-ethoxymethylindole were approximately as active as I3C in the cell cycle arrest response. This study establishes the first I3C structure activity relationship for cytostatic activities, and implicates I3C-based N-alkoxy derivatives as a novel class of potentially more potent experimental therapeutics for breast cancer (University of California, Berkeley). Bitter melon juice was analyzed at the Agricultural Diagnostic Center (CTAHR, Honolulu, HI) for its physical properties and mineral contents. In our laboratory we have undertaken to identify the bioactive compounds in whole BM juice, using HPLC. We have so far identified various polyphenols and flavanoids in BMJ. We have also undertaken bioactivity guided fractionation of BMJ by fractionating BMJ using methanol, ethyl acetate, butanol and aqueous fractions (University of Hawaii). OBJECTIVE 4. Modifying foods is an increasingly important strategy to improve nutrition and safety. Therefore, we will improve food safety by developing approaches to increase beneficial or decrease adverse effects of bioactive food constituents and microbial contaminants. The control of Clostridium perfringens spores by green tea leaf extracts containing low (GTL) and high (GTE) catechin levels during abusive cooling of meats was investigated. The treatment protocol resulted in significant increases in germination and outgrowth of C. perfringens in the meats. At 2% GTE, significant (p < 0.05) inhibition of growth occurred at all chill rates for cooked ground beef, chicken or pork. These results suggest that widely consumed catechins from green tea can reduce the potential risk of C. perfringens spore germination and outgrowth during abusive cooling of ground beef, chicken, or pork (USDA-ARS, Albany). The bactericidal activity of several antimicrobial wine recipes was examined. The recipes consisting of red and white wine extracts of oregano leaves with added garlic juice and oregano oil were tested against the following foodborne pathogens: Bacillus cereus, Escherichia coli O157:H7, Listeria monocytogenes, and Salmonella enterica. It was found that several combinations of the naturally occurring plant-derived ingredients rapidly inactivated the four pathogens. Polyphenolic compounds isolated by chromatography from red wine exhibited high antimicrobial activity at nanogram levels against two strains of Bacillus cereus. Wines appear to be useful solvents for plant-derived antimicrobial formulations to reduce pathogens in foods (USDA-ARS, Albany). HPLC and LC/MS methods were developed to be used in studies to measure the distribution of piperine isomers in four commercial ground black peppers, two from the United States and the other two from Korea after exposure to fluorescent light. The results establish the utility of the HPLC method for simultaneous analysis of the four isomers both in pure form and in black pepper extracts (USDA-ARS, Albany). A Southern analysis of banana strains of Fusarium verticillioides did not detect genes in the fumonisin biosynthetic gene (FUM) cluster but did detect genes flanking the cluster. The flanking genes included portions of FUM21 and FUM19, which are the terminal genes at each end of the FUM cluster. PCR analysis confirmed absence of the cluster in all banana strains examined. Cotransformation of a banana strain with two overlapping cosmids, which together contain the entire FUM cluster, yielded fumonisin-producing transformants that were pathogenic on maize seedlings. Together, the data indicate that fumonisin production may have been lost by deletion of the FUM cluster in the banana population of F. verticillioides but that fumonisin production could be restored by molecular genetic complementation. The results also indicate that fumonisin production by F. verticillioides is required for development of foliar disease symptoms on maize seedlings (USDA-ARS, Athens). Studies were conducted to determine the accumulation of fumonisins and sphingoid bases and their metabolites in leaf tissue of various maize cultivars. A simple and rapid method for analysis of fumonisins, sphingoid bases and sphingoid base-1-phosphates in maize leaf tissue was developed. In preliminary studies testing the method it was found that varieties of maize resistant to the mold Fusarium verticillioides- induced seedling disease did not accumulate high levels of fumonisins or sphingolipid metabolites in leaf tissue. This was not the case in the susceptible variety suggesting that both sphingolipid metabolism and fumonisin accumulation were critical for disease development in maize seedlings. Only one structural form of fumonisin (FB1) accumulated in leaf tissue (USDA-ARS, Athens). A study was done to determine how the presence of maize matrix during nixtamalization (cooking in alkaline water) affects fumonisin concentration and in vivo toxicity (rodent bioassay). Mechanism-based biomarkers of exposure were used to confirm the toxicity findings. The data from this model study indicate that the presence of maize matrix during nixtamalization reduces bioavailability and toxicity beyond that achieved by nixtamalization in the absence of the maize matrix. These results confirm that the nixtamalization process significantly reduces the risk of fumonisin exposure and that methods to optimize the nixtamalization process can be developed using mechanism-based toxicity assessment.

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. (2005) Soy processing affects metabolism and disposition of dietary isoflavones in ovariectomized Balb/c mice. J. Agric. and Food Chem. 53(22):8542-8550. Carter, O., Wang, R., Dashwood, W.M., Orner, G.A., Fisher, K.A., Lohr, C.V., Pereira, C.B., Bailey, G.S., Williams, D.E. and Dashwood, R.H. (2007) Comparisons of white tea, green tea, epigallocatechin-3-gallate and caffeine as inhibitors of PhIP-induced colonic aberrant crypts. Nutr. Cancer 58(1), 1-6. Choi, S. P., Kang, M. Y., Koh, H. J., Nam, S. H., and Friedman, M. (2007) Anti-allergic activities of pigmented rice bran extracts in cell assays. J. Food Sci. 72 (9). S719-S727. Coulombe, R.A. and Yip, S.M.. (2007) Heterologous expression of a cytochrome P450 from turkey liver that activates aflatoxin B1. In Poisonous Plants: Global Research and Solutions (K. Panter, T. Wierenga, J. Phister, eds.) CAB International, London. pp. 82-88. DeAssis, S, Wang, M, Goel, S, Foxworth, A., Helferich, W.G. and Hilakivi-Clarke, L. (2006). Increased carcinogen-induced mammary tumorigenesis and activation of MAPK in obese (fa/fa) Zucker rats exposed to pregnancy hormonal environment. J. Nutr. 136(4):998-1004. Degner S.C., M.Q. Kemp, Bowden GT, and Romagnolo, D.F. (2006) Conjugated Linoleic Acid AttenuatesCyclooxygenase-2 Transcriptional Activity via an Anti-AP-1 Mechanism in MCF-7 Breast Cancer Cells. J. Nutr.136:421-427. Degner SC, Kemp MQ, Hockings JK, and Romagnolo,D.F. (2007) Cyclooxygenase-2 promoter activation by the aromatic hydrocarbon receptor in breast cancer MCF-7 cells: repressive effects of conjugated linoleic acid. Nutr Cancer. 59(2):248-57. Friedman, M. (2007) Overview of antibacterial, antitoxin, antiviral, and antifungal activities of tea flavonoids and teas. Mol. Nutr. Food Res. 51 (1): 116-134. Friedman, M., Henika, P. R., Levin, C. E., and Mandrell, R. E. (2007) Recipes for antimicrobial wine marinades against Bacillus cereus, Escherichia coli O157:H7, Listeria monocytogenes, and Salmonella enterica. J. Food Sci. 72 (6): M207-M213. Friedman, M., Mackey, B. E., Kim, H. J., Lee, I. S., Lee, K. R., Lee, S. U., Kozukue, E., and Kozukue, N. (2007) Structure-activity relationships of tea compounds against human cancer cells. J. Agric. Food Chem. 55 (2): 243-253. Friedman, M., McQuistan, T., Hendricks, J. D., Pereira, C., and Bailey, G. S. (2007) Protective effect of dietary tomatine against dibenzo[a,l]pyrene (DBP)-induced liver and stomach tumors in rainbow trout. Mol. Nutr. Food Res. 51 (12), 185-1491. Gray, J. S., and Pestka, J. J. (2007). Transcriptional regulation of deoxynivalenol-induced IL-8 expression in human monocytes. Toxicol. Sci. 99(2), 502-511. Guarisco, J.A., Hall, J.O., and R.A. Coulombe, Jr. (2007) Butylated hydroxytoluene reduces aflatoxin B1 bioavailability and hepatic adduct formation in turkeys. In Poisonous Plants: Global Research and Solutions (K. Panter, T. Wierenga, J. Phister, eds.) CAB International, London. pp. 197-202. Heemstra, J. M., Kerrigan, S. A., Doerge, D. R., Helferich, W. G. and Boulanger, W. A. (2006) Total synthesis of (S)-equol. Org. Lett.Vol. 8, No. 24, 5441-5443. Hill, N.S., Schwarz, L.S., Dahleen, L.S., Neate, S.M., Horsley, R., Glenn, A.E., and O'Donnell, K. (2006). ELISA analysis for Fusarium in barley: Development of methodology and field assessment. Crop Science 46: 2636-2642. Hockings J.K., Thorne P.A., Kemp M.Q., Morgan S.S., Selmin O. and Romagnolo D.F. (2006) The Ligand Status of the Aromatic Hydrocarbon Receptor Modulates Transcriptional Activation of BRCA-1 Promoter by Estrogen. Cancer Research, 66:1-9. Hsu JC, Dev A, Wing A, Brew CT, Bjeldanes LF and 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. 72(12):1714-23. Islam, Z., Amuzie, C. J., Harkema, J. R., and Pestka, J. J. (2007). Neurotoxicity and inflammation in the nasal airways of mice exposed to the macrocyclic trichothecene mycotoxin roridin a: kinetics and potentiation by bacterial lipopolysaccharide coexposure. Toxicol. Sci. 98(2), 526-541. 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. Ju, Y. H., Fultz J, Allred K.F., Doerge D.R., and Helferich, W.G. (2006) 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 27(4):856-63. Ju, Y.H., Allred, K.F., Allred, C.D., and Helferich, W.G., (2006) Genistein Stimulates Growth of Human Breast Cancer Cells in a Novel, Postmenopausal Animal Model, with Low Plasma Estradiol Concentrations. Carcinogenesis 27(6):1292-9 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. 134(5):1145-51. Juneja, V. K. and Friedman, M. (2007) Carvacrol, cinnamaldehyde, oregano oil, and thymol inhibit Clostridium perfringens spore germination and outgrowth in ground turkey during chilling. J. Food Protection. 70 (1): 218-222. Juneja, V. K., Bari, M. L., Inatsu, Y., Kawamoto, S., and Friedman, M. (2007) Control of Clostridium perfringens spores by green tea leaf extracts during cooling of cooked ground beef, chicken, and pork. J. Food Protection 70 (6): 1429-1433. Kemp, M.Q., Thorne, P.A., Liu, W., Kane, M.D., Selmin, O. and Romagnolo, D.F. (2006) Expression Profiles Induced by Polycyclic Aromatic Hydrocarbons: The Transferrin Receptor as an Aromatic Hydrocarbon Receptor-inducible Biomarker of Exposure. Environmental Molecular Mutagenesis 47:518-526. Kirui, G. K., Misra, A. K., Olanya, O. M., Friedman, M., El-Bedewy, R., and Ewell, P. T. (2007) Glycoalkaloid content of some superior potato (Solanum tuberosum L) clones and commercial cultivars. Archiv. Phytopathology and Plant Protection. Online (1): 1 - 11. 2007. Kozukue, N., Park, M.-S., Choi, S.-H., Lee, S.-U., Ohnishi-Kameyama, M., Levin, C. E., and Friedman, M. (2007) Kinetics of light-induced cis-trans isomerization of four piperines and their levels in ground black peppers as determined by HPLC and LC/MS. J. Agric. Food Chem. 55 (17): 7131-7139. Li, M., Harkema, J. R., Cuff, C. F., and Pestka, J. J. (2007). Deoxynivalenol exacerbates viral bronchopneumonia induced by respiratory reovirus infection. Toxicol. Sci. 95(2), 412-426. 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. 217(1), 76-85. 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. Morgavi, D.P. and Riley, R.T. (2007) Fusarium and their toxins: Mycology, occurrence, toxicity, control and economic impact. Animal Feed Science and Technology 137: 199-200. Morgavi, D.P. and Riley, R.T. (2007) An historical overview of field disease outbreaks known or suspected to be caused by consumption of feeds contaminated with Fusarium toxins. Animal Feed Science and Technology 137: 201-212. 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. 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