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United States Department of Agriculture

Agricultural Research Service


Location: Food Components and Health Laboratory

Project Number: 1235-52000-056-00
Project Type: Appropriated

Start Date: May 27, 2004
End Date: Apr 30, 2009

Obj. 1. Evaluate the role of nitric oxide in the outcome of coxsackievirus B3-induced acute myocarditis in selenium (Se) and/or vitamin E-deficient mice as a model of human inflammatory heart muscle disease. Obj. 2. Clarify the mechanism whereby dietary iron overload in the host leads to severe and unusual genomic mutations in coxsackievirus B3 inoculated into mice deficient in vitamin E. Obj. 3. Define biomarkers that differentiate between the proper elevated cancer chemopreventive dose of Se and the threshold toxic dose of Se through the application of proteomic discovery techniques.

This project plan consists of three parts, each of which will examine the relationship between selenium and/or vitamin E status and human health. We will investigate the role of nitric oxide (NO) in the course of infection with the cardiotrophic coxsackievirus in mice as a model of human acute myocarditis. We hypothesize that greater heart muscle damage will occur in virus-infected and Se-deficient mice because viral infection and Se deficiency both increase NO in vivo. The second part will study the mechanism whereby dietary iron overload causes changes in the genome of coxsackievirus inoculated into vitamin E-deficient mice. This could serve as a model for various human diseases that are increased by iron excess including liver cancer and hepatitis. The third part will utilize proteomics in an attempt to characterize biomarkers that can distinguish between the elevated doses of selenium needed to demonstrate its cancer chemopreventive properties versus the dose that results in chronic selenium poisoning. If increased intakes of selenium are ever advocated as a cancer preventative public health measure, better ways of assessing selenium overexposure will be needed.

Last Modified: 4/24/2014
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