Johns Hopkins chemists have discovered a new way to
sabotage DNA's ability to reproduce, a finding that could
eventually lead to the development of new anti-cancer drugs
and therapies.
The method could enable future doctors to target
treatment more precisely, rather than directing
chemotherapeutic medication or radiation to tumors through
a scattershot approach, said Marc Greenberg, a
chemistry
professor in the Zanvyl Krieger School of Arts and
Sciences, who presented his team's findings on March 14 at
the 229th American Chemical Society Meeting in San
Diego.
"What we did was to identify a way to create a very
damaged form of DNA that is often more deadly to the cell
than other types of damage," Greenberg said. "That's how
many anti-tumor medications — medications such as
mitomycin c — work: They kill off tumors by linking
up with the cancer cells' DNA and sticking its genetic code
together so it dies. Our discovery takes that a step
further, establishing that there is a way to efficiently
create this type of damage by modifying the DNA itself."
In the lab, Greenberg and his team used organic
chemistry to create a synthetic, double-stranded DNA with
special chemical characteristics and exposed it to long
wavelength light that selectively switches on the DNA
damage process.
He said that the synthetic DNA is very similar to that
which is produced when cells are exposed to radiation, with
one exception: Greenberg's team's DNA was damaged at only
one place on its chain, allowing the researchers to study
it and learn about that particular chemical pathway in
detail.
"Exposing DNA to radiation is like hitting a fine
piece of crystal stemware with a hammer. It shatters, and
looking for a particular chemical pathway is like looking
for a needle in a haystack," the chemist explained. "What
we did was more like carrying out a precision attack. It
let us get a closer look."
The team's work was funded by the National Institute
of General Medical Sciences at the National Institutes of
Health.
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