Duke to Study Superfund Chemicals' Impacts on Biological Systems and Environment

Duke University Medical Center
Wednesday, 31 May 2000

Researchers at Duke University's environment, medical and engineering schools will join forces to study how chemicals regulated under the U.S. Superfund program affect the biology of reproduction and development as well as how these toxins interact with soils and water at contaminated sites.

Approved for more than $6 million in funding over five years through the National Institute of Environmental Health Sciences, the new Duke University Superfund Basic Research Center will address "an area of enormously growing concern for such chemicals in the environment," said principal investigator and center director Richard DiGiulio in an interview.

"More and more we're recognizing that the early stages in the lives of humans and other organisms are particularly sensitive," said DiGiulio, a professor of environmental toxicology at Duke's Nicholas School of the Environment.

"Everyone thinks that Superfund research is about the identification and cleanup of chemicals at Superfund locations," added Theodore Slotkin, a Duke Medical Center professor of pharmacology, cancer biology and psychiatry who is the center's co-principal investigator. "This is a really different approach: the issue of biological effects and underlying mechanisms."

Slotkin noted that many chemicals listed under the Superfund act, which provides funds to contain and remove hazardous chemicals from abandoned plants and dumpsites, are also "compounds that are in everyday use, such as common insecticides."

One example to be intensely studied is chlorpyrifos, a widely used organophosphate insecticide that, while considered less of a threat to humans and the environment than older types like DDT, may have been underinvestigated to know its true impact, Slotkin said. He noted that a recent study commissioned by the U.S. Environmental Protection Agency identified the presence of organophosphates in the urine of school children, presumably the result of environmental exposure.

The Duke center's investigators will study the effects of such compounds on the developing brain, as well as on the growth and differentiation of other cells and tissues, by enlisting the aid of two aquatic animals: zebrafish and killifish.

Fast-growing zebrafish go through embryonic development in just three days, and researchers have developed a number of transgenic varieties that can produce fluorescent proteins in response to changes in organs and systems such as might be induced by Superfund chemicals. And, because some zebrafish breeds are quite transparent, researchers can view the effects of these changes in living animals.

"If you wanted to do research with humans or other mammals, it would be nice if you had some magic microscope that would allow you to watch all the events occurring as the embryo was developing," said Elwood Linney, a professor of microbiology and professor of the environment who will provide the transgenic fish as head of the center's "research core."

"If we make transgenic fish that express the right fluorescent protein, we can see that, we can capture it in time and in three dimensions, and then use computer technology to reconstruct the changing pattern of gene expression," he said.

Zebrafish are native to India's Ganges River and thus may not be environmentally relevant to U.S. waters. So DiGiulio's lab also will evaluate how Superfund chemicals affect growth and development in killifish, "a very common estuarine species that is a major part of the food chain in North Carolina and other East Coast estuaries," he said.

The fish studies will in turn help Slotkin's team investigate the effects of Superfund chemicals on the brain development of laboratory rodents, which serve as mammalian research surrogates for humans.

"One of the big problems you have with compounds whose long-term effects on development are unknown is knowing what to look for," Linney said. "There are thousands of things you could look for, but no one has the time to explore all of those."

Using fast-breeding fish populations to learn when damage occurs and what biological processes are affected "allows us to immediately select the right end points in a mammalian system," he added. "There are event and developments that are common to all vertebrate systems, whether they're fish or humans."

Jonathan Freedman, a Nicholas School assistant professor of environmental toxicology, will use both zebrafish and cultured mammalian cells to evaluate how selected Superfund chemicals may alter specific genetics mechanisms that control early growth.

Dharni Vasudevan, a Nicholas School assistant professor of environmental chemistry, will team up with Zbigniew Kabala, an associate professor of civil and environmental engineering at Duke's Pratt School of Engineering, to study how lesser-studied chemicals like chlorpyrifos might change and migrate over time at actual Superfund sites at Plymouth and Washington, N.C.

As part of that work, the pair and their students have already begun evaluating whether a commercially available tracer dye called Rhodamine WT, which unlike hazardous chemicals is EPA-approved for injection into the ground, can mimic the behavior of the actual Superfund toxins in those sites' soils and underlying drainage channels. The center's "outreach core," headed by Marie Lynn Miranda, a Nicholas School associate professor for the practice of environmental policy, will work toward disseminating the results of the research, as well as assessing exposure risks more generally in North Carolina and nationally.

For more information, or to contact Duke University Medical Center, see their website at: www.mc.duke.edu