Project Number: 6612-42000-012-00
Project Type: Appropriated

Start Date: Feb 08, 2011
End Date: Feb 07, 2016

Objective:
1. Determine the biochemical and molecular basis for the species specificity of fumonisins using animal models. 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.

Approach:
1. Conduct dose-response studies to determine the minimum oral dose of FB1 that disrupts sphingolipid metabolism and induces toxicity (increased apoptosis) in rat kidney and mouse liver. 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.