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A team of Dartmouth Medical School
(DMS) researchers has determined that low doses of arsenic disrupt the activity
of a hormone critical in development. The finding is further evidence that
arsenic at low doses (at levels found in U.S. drinking water in some areas) can
be harmful. The study appeared in the Oct. 26, 2007, online edition of the
journal Environmental Health
Perspectives (EHP), and it will be published in a forthcoming issue of
the journal.
 Jennifer Davey
and Joshua Hamilton (Photo by Joseph Mehling ’69)
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“Arsenic is a natural, yet pervasive, chemical in the environment; we can’t
seem to escape it,” says Joshua Hamilton, one
of the authors on this study and the director of the Center for Environmental Health Sciences
at Dartmouth and Dartmouth’s Superfund Basic Research Program on
Toxic Metals. “By learning how it adversely affects biological processes
and at what levels we should be concerned, we will hopefully someday be able to
mitigate its impact on human health.” Hamilton is also a professor of
pharmacology and toxicology at DMS.
Hamilton and his team, in previous work, have learned that arsenic at low
doses appears to suppress the ability of all critical steroid receptors,
including those for estrogen and testosterone, to respond to their normal
hormone signals. Chemicals that disrupt steroid hormone receptor signaling are
called endocrine disruptors. Arsenic can disrupt these hormone pathways at
extremely low doses equivalent to what many people in the U.S. have in their
drinking water.
This study set out to see whether arsenic can also disrupt the activity of
two hormone receptors that are involved in normal development—the retinoic acid
receptor and the thyroid hormone receptor, two important members of the larger
nuclear hormone receptor family. While the researchers studied the impact on
frog development, these two hormone receptors are also vital to human
development.
“I believe this is the first demonstration in an animal model that arsenic
actually disrupts a developmental process that is regulated by hormones, and it
does this at extremely low doses that are directly relevant to human exposures
of concern,” says Hamilton.
The work is funded by grants to Dartmouth from the National Institute of Environmental Health
Sciences, a component of the National Institutes of Health. Other
researchers on the paper include Jennifer C. Davey, Athena P. Nomikos, Manida
Wungjiranirun, Jenna R. Sherman, Liam Ingram, Cavus Batki, and Jean P.
Lariviere, all with, or formerly with, the Department of Pharmacology and
Toxicology at DMS.
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