Insight: Research Edition

Fall 2006

Adduct Biomarkers May Help Scientists Pinpoint Risk of Pesticide Exposure

The debate over the benefits and dangers of agricultural chemicals is one fraught with differing opinions, conflicting scientific studies and raw emotionalism. At the High Plains Intermountain Center for Agricultural Health and Safety, research is underway to better understand the effects of these environmental chemicals on humans and animals, and to develop biomarkers that can help predict health risks.

Dr. John Tessari, an Associate Professor in the Department of Environmental and Radiological Health Sciences, and his team are focusing their studies on Atrazine, one of the most commonly used herbicides in the United States and worldwide. In 2003, according to the Environmental Protection Agency, more than 77 million pounds of Atrazine were used on major crops in agricultural operations.

“The health effects of Atrazine are still being researched and debated,” said Dr. Tessari, whose analytical lab focuses on environmental chemicals. “There is a lot of controversy about cancer risks, but what we do know is that Atrazine affects reproduction by impacting the luteinizing hormone (LH) and follicle stimulating hormone (FSH). Our laboratory is researching the use of biomarkers, in this case an Atrazine adduct formed in albumin, as an early warning system of exposure in individuals who may be susceptible to long- and/or short-term health problems due to the chemical.”

An adduct is a complex that forms when a chemical, such as Atrazine, binds to a biological molecule, such as DNA or protein. Atrazine is a parent molecule that is metabolized within 24 hours in the body. It is actually one of Atrazine’s metabolites, DACT, that forms the adduct being studied. The advantage of using these protein adducts, is that they are chemically stable, have a long half-life in the body, and are not subject to repair as is DNA. Using the rat as a model, Dr. Tessari’s research team has identified the specific bound adduct to use as an “exposure biomarker” – biomarkers used to measure actual absorbed dose or internal dose and the extent of actual environmental chemical (or metabolite) in the body. His team has also identified the peptide sequence containing the adduct peptide, and is now in the verification stage of their research.

“We are extraordinarily fortunate to be one of the few universities in the nation to have the instrumentation and expertise that enables this type of proteomic work,” said Dr. Tessari. “Our Macro-molecular Resource Facility allows us to do mass spectrometry analysis using the MALDI-TOF-TOF mass spectrometer (Matrix-Assisted Laser Desorption/Ionization Time-of-Flight/Time-of-Flight), truly cutting edge technology. That, combined with the sequencing databases available via the Web, and the mapping of the human genome, is enabling us to do things we didn’t think possible five years ago.

“It’s really exciting to be a part of this and look back at how our work has completely changed – how much more we are able to do to advance human health – thanks to the technical and procedural advances that are enabling us to analyze cellular interaction.”

Working on a five-year grant from the Environmental Protection Agency, Dr. Tessari eventually hopes to move the research program in novel biomarkers for pesticides from animal to human studies.