Researcher's Persistence, Collaboration Reveal Clues to Environmental Hazards

Most answers to researcher's questions are not found quickly, instead each experiment, each test and each collaboration with colleagues completes another piece of the puzzle. Researchers in several departments and Centers of Excellence at the Arizona Health Sciences Center (AHSC) have worked together for nearly two decades to understand the root causes of a devastating birth defect linked to groundwater contamination.

Normally, scientists observe a phenomenon in a laboratory and then try to apply it to the real world. In this case, researchers observed a real world phenomenon and then reproduced it in the laboratory to achieve a clearer understanding.
In 1980, researchers noticed an abnormally high number of children being born with congenital heart defects. Many of the children were born to mothers who lived in Southern Arizona, in just one zip code. In 1981 after drinking water wells contaminated with Trichloroethylene (TCE) were closed, the rate of heart defects decreased.

Epidemiological studies confirmed an association between women in their first trimester who were exposed to drinking water contaminated by TCE and an increased prevalence of heart defects in their children. Once the contaminated wells were closed, the rate of heart defects decreased, but researchers still didn't know exactly if and how TCE related to the malformations.

Initial experiments were performed as a collaboration between investigators in the Division of Pediatric Cardiology and the Department of Anatomy. Laboratory studies showed that high doses of TCE could produce heart defects, but these experiments were time consuming and costly. To answer one question of critical importance, whether exposure at levels of TCE found in the drinking water could produce heart defects, required a new approach. A research group focused on normal heart development was enlisted to look for changes produced by exposure to TCE.

TCE is our nation's most frequently detected contaminant in groundwater. A man-made substance used since the early 1950's for a variety of metal degreasing and cleaning operations, TCE also is used as a starting material for other man-made chemicals.

The current collaboration brings together faculty in the Superfund Basic Research Program at the UA College of Pharmacy's Center for Toxicology with investigators in the UA College of Medicine's Departments of Pediatric Cardiology, Pharmacology and Toxicology, and Cellular Biology and Anatomy. Funded by a grant from the National Institute of Environmental Health Sciences in association with the Environmental Protection Agency, the current research is headed by Principal Investigator Paula D. Johnson, DVM., and co-investigators Ornella Selmin, Ph.D., and Raymond Runyan, Ph.D.

Building on the previous TCE studies, the researchers are looking at the cellular and molecular mechanisms that lead to cardiac malformations.

"The heart develops first, so we know that a range of cardiac defects can occur very early in the first trimester," says Dr. Selmin. "Our studies show a correlation between TCE and heart defects, but we want to make a direct link between the two."

Investigators believe that the heart defects may potentially be attributed to disruptions in specific populations of cells in the developing heart. Researchers also want to know whether different doses of TCE may bring about different heart defects.

"The results will tell us more about how sensitive heart cells are to TCE exposure," says Dr. Selmin. "Each piece of the puzzle advances our knowledge of the basic processes of heart development and the role of TCE in the destruction of those processes."

The impact of these findings reaches far beyond one zip code in one Southern Arizona neighborhood. TCE is found in public and private drinking water supplies throughout the United States and the world. Understanding precisely how it can affect the human body directly benefits the global community.

"It's been an incredible collaboration from the beginning, taking a real world observation back to the lab to learn so much" says Dr. Selmin, who added her talents as a molecular and environmental toxicologist to the research in 1996.

"This really puts science to work for everyone."