Development of Novel Biomarkers for Pesticides in EPA Region VIII
Principal Investigator: John Tessari, Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO
The overall plan of this research is to test the hypothesis that we can develop practical applications for the direct measurement of biological events or responses that result from human exposure to agricultural chemicals. These measurements are conveniently called “biological markers” or “biomarkers”. The real importance of these biomarkers is that they reflect molecular and or cellular alterations that occur along the temporal and mechanistic pathways connecting ambient exposure to a chemical and eventual human disease. The recent surge of interest in this field has been driven by technical advances in analytical and molecular genetic techniques and by the recognition that “classical toxicology” and epidemiology may not be able to alone solve critical questions regarding the cause of exposure to environmental chemicals. The ultimate goal is to predict the risk of, and possibly help prevent, the onset of disease.
We have focused our initial work using the herbicide Atrazine and developing analytical methods to identify and measure protein adducts using hemoglobin in Sprague Dawley rats, and humans. The advantages to using these particular protein adducts are related to their chemical stability and their long half-life in the body. They can be detected for up to four months (the life-span of a human red blood cell) after exposure, and they are not subject to repair as is DNA or other tissues.
Hemoglobin consists of approximately 3.8% heme and 96.2% globin, therefore we extracted the globin from rodent and human blood and using in-vivo and in-vitro techniques and a specific very sophisticated instrument we have identified a chemically bound product of the major metabolite of atrazine.
We will use these specific bound adducts as a type of “biomarkers” called “exposure biomarkers”. Exposure biomarkers are used to measure actual absorbed dose or internal dose and the extent of actual environmental chemical (or active metabolite) to the target site in the body.
We hope the development and validation of potential biomarkers may be used to identify the early stages of health impairment and help to understand basic mechanisms of chemical exposure and the beginnings of their practical application for risk assessment and environmental health management.