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

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Duke Health News 919-660-1306

DURHAM, N.C. - 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.

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