2013 Annual Report
2. Determine the dietary “no observed effect” and “lowest observed effect levels” for neural tube defect induction and determine the dose-response thresholds for elevation in sphingolipid biomarkers in blood spots and fumonisins in urine using animal models.
3. Determine the relationship between fumonisin consumption, urinary fumonisin (exposure biomarker) and changes in sphingolipids in blood spots (effect biomarker) in human populations consuming corn.
4. Determine the specific mechanism(s) by which fumonisins are readily taken up by corn plant roots and yet have limited translocation into above ground vegetative tissues.
5. Determine the effectiveness of alkaline cooking for reducing the toxic potential of fumonisin-contaminated whole kernel corn.
2. Conduct dose-response studies in susceptible mouse strains to determine the thresholds for changes in biomarkers of exposure and effect and induction of neural tube defects.
3. Conduct epidemiological studies to identify humans consuming large amounts of corn-based foods in communities where FB is infrequently detected and frequently detected and sample and analyze urine (FBs) and blood spots (sphingolipids).
4. Conduct dose response studies to determine FB1 affects on plant transpiration and levels of sphingoid bases and their 1-phosphates in roots and aerial tissues in FB1-sensitive and -insensitive genotypes of corn.
5. Utilize FB-contaminated whole kernel corn to determine the processing conditions that maximize FB1 reduction using chemical analysis and in vivo animal bioassays.
Objective 2: We are conducting studies on the role of dietary folate in induction of neural tube defects (NTD) in mouse. Studies confirm NTD induction by fumonisin B1 (FB1) is reduced in NTD-sensitive LM/Bc mice when fed folate deficient diets for five weeks prior to mating. The protection is associated with an 80 percent reduction of maternal red blood cell folate in mice fed the deficient diet. Based on our earlier work on interactions between folate and FB1, the finding is counterintuitive and suggests the activity of folate in this mouse model with FB1 treatment is much more complicated than previously believed.
Objective 3: A survey of fumonisin (FB) contamination in corn in Guatemala was completed. Corn samples (640) were analyzed for FB and aflatoxins (AFB). High levels of AFB and FB were detected in corn from the Petén. High levels of FB, but not AFB, were detected in the Chiquimula and Santa Rosa and very low levels of FB and AFB were detected in the Sacatepéquez. Blood (n=390) and urine (n=390), as well as corn (n=30) for human consumption, were analyzed from Sacatepéquez, Chiquimula, and Santa Rosa. Analysis of the urinary FB biomarker confirmed low exposure in Sacatepéquez and high exposure in Chiquimula and Santa Rosa. The sphingolipid biomarkers in blood are being analyzed.
Objective 4: An experimental system was developed to assess the physiological responses and molecular/cellular mechanisms that confer sensitivity/insensitivity to fumonisin B1 (FB1) in maize. Utilizing mutant strains of Fusarium verticillioides, we demonstrated that FB1 accumulates in leaves of the susceptible cultivar Silver Queen without colonization of aerial tissues. Wild-type F. verticillioides colonized leaves and accumulated FB1. Thus, in plant-fungal interactions with the susceptible cultivar, a mechanism for FB1 accumulation exists apart from fungal colonization of leaf. Insensitive inbreds, B73 and W23, accumulate very little FB1 in the leaves when inoculated with wild type, suggesting these maize genotypes are more insensitive, in part, due to less accumulation of FB1. They may suppress FB1 production by the fungus. Further study comparing maize genotypes will identify mechanistic differences.
Objective 5: Studies to optimize the nixtamalization process, that will determine the minimum processing procedures (i.e., number and volume of rinses) needed to achieve a significant protective effect and define fumonisin concentrations or other factors limiting reductions, are pending the identification of a suitable source of corn.
Gelineau-Van Waes, J., Rainey, M.A., Maddox, J.R., Voss, K.A., Sachs, A.J., Gardner, N.M., Wilberding, J.D., Riley, R.T. 2012. Increased sphingoid base-1-phosphates and failure of neural tube closure after exposure to fumonisin or FTY720. Birth Defects Research Part A: Clinical and Molecular Teratology. 94(10):790-803.
Riley, R.T., Voss, K.A., Showker, A.J., Torres, O., Matute, J., Maddox, J.R., Rainey, M., Gardner, N.M., Sachs, A., Gregory, S.G., Ashley-Koch, A.E., Krupp, D., Gelineau-Van Waes, J. 2012. Development of biomarkers to assess fumonisin exposure and birth defects. In: Binder, E.M., editor. Proceedings of the World Nutrition Forum, October 10-13, 2012, Marina Bay, Singapore. p. 249-256.
Pitt, J.I., Wild, C.P., Gelderblom, W., Miller, J., Riley, R.T., Wu, F., Bann, R.A. 2012. Improving public health through mycotoxin control. Lyon, France: International Agency for Research on Cancer. Publication No. 158. 162 p.
Bondy, G.S., Mehta, R., Caldwell, D., Coady, L., Armstrong, C., Savard, M., Miller, J., Chomyshyn, E., Bronson, R., Zitomer, N.C., Riley, R.T. 2012. Effects of long term exposure to the mycotoxin fumonisin B1 in p53 heterozygous and p53 homozygous transgenic mice. Food and Chemical Toxicology. 50(10):3604-3613. DOI: 10.1016/j.fct.2012.07.024.
Voss, K.A., Riley, R.T., Moore, N.D., Burns, T.D. 2013. Alkaline cooking (nixtamalisation) and the reduction in the in vivo toxicity of fumonisin-contaminated corn in a rat feeding Bioassay. Food Additives & Contaminants: Part A. 30(8):1415-1421. DOI: 10.1080/19440049.2012.712064.
van der Westhuizen, L., Shephard, G.S., Gelderblom,, W.A., Torres, O., Riley, R.T. 2013. Fumonisin biomarkers in maize eaters and implications for human disease. World Mycotoxin Journal. DOI: 10.3920/WMJ2013.1589.