A Dartmouth Medical School research team recently pinpointed the protein mechanism used by arsenic to activate the growth of bladder, lung and skin cancers, according DMS professor of community and family medicine Margaret Karagas, the leader of the study.
The team also included principal investigator David Robbins, a former DMS professor of pharmacology and toxicology, and first author Dennis Liang Fei, a DMS doctoral student.
Karagas and her team determined that arsenic whose presence is associated with higher rates of cancer can activate a secreted protein known as Hedgehog, according to a DMS press release. The protein plays an important role in embryonic pattern formation and adult tissue homeostasis. When exposed to an external stimulus like arsenic, the Hedgehog protein can activate the growth of tumors in mammals.
In an effort to understand what Karagas called a "global health issue" in an interview with The Dartmouth, the team combined experimental information from cell cultures with results obtained through studies of populations exposed to arsenic.
"My interest from an epidemiologic standpoint and [Robbins'] expertise on Hedgehog signaling research created a collaboration of bench science and population science," Karagas said. "This study exemplifies how interdisciplinary work can lead to new scientific discoveries."
Previous studies have found a correlation between environmental arsenic and the development of bladder, lung and skin cancer in humans, according to a DMS press release. Karagas and her team hypothesized that the correlation was related to arsenic's role in the Hedgehog protein's signalling pathway, she said.
Higher rates of cancer have been detected in areas of the world including Taiwan, Bangladesh and Argentina where unusually high levels of arsenic are found in natural drinking water, according to the press release. By consuming natural water, millions of people are exposed to arsenic, Karagas said, adding that the full effects of this exposure are still not entirely known.
Although arsenic exposure is most extreme in other countries, high environmental arsenic levels are also a locally relevant issue because abnormal levels of arsenic have been detected in private New Hampshire wells, Karagas said. Arsenic concentrations of more than 10 grams per liter commonly contaminate wells and other forms of private, unregulated drinking water throughout the United States, according to the DMS release.
Expanding research about the effects of arsenic exposure may help "determine whether the current standards for maximum arsenic levels are really safe, and might also encourage people to have their private water systems tested," Karagas said.
Karagas' next research project will explore the consequences of arsenic exposure on fetal development and pregnant women, she said. The National Institute for Environmental Health Sciences and the U.S. Environmental Protection Agency recently gave Karagas funding for the venture, she said.
