Arsenic exposure has long been linked to cancer, but just how the toxic element triggers tumor growth has been unknown.

A new study, published online February 23 in the journal Cancer Research, describes for the first time the impact of arsenic on crucial signals among the body's cells—a potentially potent discovery for the 100 million people worldwide whose drinking water exceeds arsenic levels recommended by the World Health Organization.

The researchers, led by Dennis Liang Fei of the Department of Pharmacology and Toxicology at Dartmouth Medical School in Hanover, N.H., were tipped off by recent work that had shown that the Hedgehog protein signaling pathway (which plays a role in embryo development and likely some cancers) was often overactive in many of the same cancers to which arsenic has been tied—in particular bladder cancer.

Through study of cell cultures, tumors in mice and tumors from 265 bladder cancer patients, the team established that "arsenic is able to activate Hedgehog signaling," they noted in the paper describing the research. And "chronic activation of Hedgehog signaling by arsenic might contribute to the development of a subset of these tumors," they argued. 

They found that both acute and chronic low-levels of arsenic exposures led to the overactive signaling. And in studying the bladder cancer patients, the researchers discovered that "high levels of arsenic exposure are associated with high levels of Hedgehog activity."

This new knowledge will add "insight into the etiology of arsenic-induced human carcinogenesis," the researchers wrote. And though more questions remain, the findings might eventually be "relevant to millions of people exposed to high levels of arsenic."

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