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Genomic Test Could Help Detect Radioactivity Exposure from Terrorist Attacks

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Duke Health News 919-660-1306

DURHAM, N.C. -- In the event of a nuclear or radiological
catastrophe -- such as a nuclear accident or a "dirty bomb" --
thousands of people would be exposed to radiation, with no way
of quickly determining how much of the deadly substance has
seeped inside their bodies. Scientists at Duke University
Medical Center have developed a new blood test to rapidly
detect levels of radiation exposure so that potentially
life-saving treatments could be administered to the people who
need them most.

There appears to be a critical window of 48 to 72 hours for
administering treatments aimed at halting the devastating
effects of radiation, said senior study investigator John
Chute, M.D., an associate professor of medicine in the Duke
Adult Bone Marrow and Stem Cell Transplant Program. But
existing tests for measuring radiation exposure take several
days and are not practical for testing large numbers of
patients at once.

"If a terrorist attack involving radioactive material were
to occur, hospitals might be overrun with people seeking
treatment, many of whom have actually been exposed and many of
whom are simply panicked," Chute said. "We have to be able to
efficiently screen a large number of people for radiation
exposure in order to respond effectively to a mass casualty
event."

The new test scans thousands of genes from a blood sample to
identify distinct genomic "signatures" reflecting varying
radiation doses. Patients can then be handled according to
whether they received no exposure to radiation, an intermediate
level of exposure that may respond to medical therapies or an
inevitably lethal dose.

The researchers published their findings April 3, 2007, in
the journal Public Library of Science (PLoS) Medicine. The
research was funded by the National Institute of Allergy and
Infectious Diseases.

High doses of radiation can damage or wipe out a person's
blood and immune systems, leading in some cases to bone marrow
failure accompanied by infections, bleeding and a potentially
heightened lifetime risk of cancer. Since the symptoms of
radiation exposure can take days or weeks to develop, it could
be difficult to identify individuals truly exposed without a
practical test to make this distinction, the researchers said.
Current treatments for radiation exposure aim to bolster the
blood and immune systems before the damage becomes too
severe.

Previous studies by researchers at the Duke Institute for Genome Sciences &
Policy
have used genomic technology to identify genes that
can predict prognosis and response to chemotherapy within
several types of cancers. In the current study, the Duke team
used a similar strategy to determine which genes change in
response to different levels of radiation exposure.

The researchers subjected mice to low, intermediate and high
doses of radiation and looked for the impact of each dose on
specific genes in the blood. They found that each dose resulted
in distinct profiles, or signatures, representing 75 to 100
genes that could be used to predict the degree of exposure.

They also analyzed blood from human patients receiving bone
marrow transplants who were treated with high doses of
radiation prior to transplant and found specific gene profiles
that distinguished the individuals that were exposed to
radiation from those that were not with an accuracy of 90
percent.

"The goal now is to refine this test to the point that if a
disaster were to occur, we could draw blood from thousands of
people and have results back in time for treatment to have
effect," said Joseph Nevins, Ph.D., a professor of molecular
genetics and a researcher at the Duke Institute for Genome
Sciences & Policy and co-investigator on the study.

These findings also could point to new treatments for
victims of a radiological catastrophe, said lead study
investigator Holly K. Dressman, Ph.D., an associate professor
of molecular genetics and a researcher at the Duke Institute
for Genome Sciences & Policy. "By identifying genes that
are major players in the response to radiation, we hope to
compile a list of future targets for protection against its
harmful effects."

The researchers are currently refining the test by looking
at the effects of time from exposure, gender, age and
additional genetic factors on the ability of the test to
predict radiation dose, Dressman said.

Other researchers participating in the study were Geoff S.
Ginsburg of the Duke Institute for Genome Sciences & Policy
and Garrett G. Muramoto, Nelson J. Chao, Sarah Meadows and Dawn
Marshall of the Duke Department of Medicine, Division of
Cellular Therapy.

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