While the correlation between arsenic exposure and cancer tumors such as those derived from bladder, lung and skin is well established, the molecular mechanisms driving this connection has remained unclear.
Using experimental data from cell cultures and results of epidemiologic studies, the researchers found that arsenic activates the Hedgehog signaling by decreasing the stability of the repressor form of GLI3, which is one of the transcription factors that regulate Hedgehog activity. Researchers also found high levels of arsenic exposure associated with high levels of Hedgehog activity.
Arsenic is a well-known environmental toxin and carcinogen. Studies to date have shown that individuals who live in arsenic contaminated areas of the world exhibit an elevated cancer rate. In many regions of the world, notably Taiwan, Bangladesh and Argentina, high levels of arsenic are detected in drinking water. Here in the United States arsenic concentrations above the current maximum contaminant level of 10 μg/L are often found in private, unregulated drinking water systems.
"Constitutive Hedgehog signaling has been implicated in a wide spectrum of solid tumors," said Anthony Capobianco, Ph.D., editorial board member of Cancer Research. "This group observed increased Hedgehog activity in a large set of human bladder tumors. Interestingly, they also detected a strong correlation between high-level Hedgehog activity and arsenic exposure in this cohort of bladder cancer patients, supporting their mechanistic findings."
"This report is the first to link arsenic exposure to activation of the signaling pathway and its potential mediator of arsenic-driven tumors," he said.
Citation: Fei et al., 'Activation of Hedgehog Signaling by the Environmental Toxicant Arsenic May Contribute to the Etiology of Arsenic-Induced Tumors', Cancer Research, February 2010; doi: 10.1158/0008-5472.CAN-09-2898
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