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Low Doses Of Arsenic Have Broad Impact On Hormone Activity – Says A Researc

ormal hormones to activate their specific receptor, as most other endocrine disruptors do," says Hamilton, who is also a professor of pharmacology and toxicology at Dartmouth Medical School. "Nor does it affect the ability of the hormone-activated receptor to move to the nucleus of the cell or to bind to DNA to initiate gene expression. Yet, somehow arsenic still strongly affects the ability of these hormone-activated receptors to regulate gene expression. There's still a lot more to learn."

The study also looked into the effects of different levels of arsenic on these receptors. At very low doses (comparable to what is found in drinking water at the current and previous U.S. regulatory limits, in the range of 5-50 ppb) arsenic enhances hormone-stimulated gene expression, by two- to three-fold. At slightly higher doses (in the range of 50-200 ppb, commonly found in drinking water from contaminated wells in New Hampshire and elsewhere in the U.S.) arsenic has the exact opposite effect, strongly and almost completely inhibiting hormone-stimulated gene expression by these receptors. This non-conventional dose-response suggests that arsenic might have very different biological effects at the lower and higher doses.

"Elucidating these complex biological effects of arsenic on hormone signaling at different doses will be critical to our overall understanding of how arsenic influences human health, and should be considered as an important component of determining the overall disease risk of people who are exposed to arsenic in their drinking water, " says Hamilton.

The work is funded by grants to Dartmouth collaborators Hamilton and Bodwell from the National Institute of Environmental Health Sciences, a component of the National Institutes of Health. Both researchers are members of the NIEHS-funded Superfund Basic Research Program at Dartmouth and Dartmouth's Center for Environmental Health Sciences. Co-authors on the study include Julie A. Go
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