Arsenic and Endocrines: New Study Suggests Disruption
Josephson, Julian, Environmental Health Perspectives
Chronic low-level human exposure to arsenic is associated with increased cancer risk. Epidemiologic studies of exposed populations in Asia and South America have shown a significant increase in the risk of skin, lung, liver, and bladder cancers, yet arsenic's carcinogenic mechanism remains unknown. Chronic exposure to arsenic also is associated with elevated risks of type 2 diabetes mellitus and vascular disease. In this issue, Ronald Kaltreider, Joshua Hamilton, and colleagues from Dartmouth Medical School in Hanover, New Hampshire, may have uncovered a clue to a central mechanism behind arsenic's myriad adverse health effects [EHP 109:245-251].
Low-level exposure to arsenic in drinking water is widespread in the United States and elsewhere. In New Hampshire, for instance, where 40% of the population's water supply comes from private wells, as much as 8% of the state (one-fifth of all private well users) may be exposed to arsenic concentrations between the U.S. Environmental Protection Agency's proposed standard of 10 parts per billion and the current standard of 50 parts per billion. At industrial sites and toxic waste sites--including over 70% of all Superfund waste sites--arsenic is usually found in combination with many other toxic chemicals, and it can leach into groundwater and find its way into drinking water.
The current study follows up on previous research that found that arsenic affects expression of the well-characterized phosphoenolpyruvate carboxykinase gene in rat liver cancer cells, reducing its responsiveness to hormone signals. Working in Hamilton's laboratory, which studies the effects of toxic metals on gene expression, Kaltreider and colleagues studied three sets of rat liver cancer cells. The first set was treated with various noncytotoxic concentrations of arsenite solution. The second was treated with a synthetic glucocorticoid hormone called dexamethasone (Dex). The third was treated with both arsenite and Dex. Glucocorticoids mediate a large array of effects. Among them are blood glucose regulation, vascular function, cell differentiation, and apoptosis, all of which are key functions in systems affected by arsenic exposure. …