Grant: Project Grant

Hundreds of millions of people world-wide are exposed to the natural element arsenic in their drinking water. This has resulted in a global public health crisis because arsenic causes cancer in humans and is correlated with other adverse health effects including diabetes and vascular disease. In Canada, arsenic "hot-spots" naturally exist with levels in well water potentially exceeding acceptable levels. As a waste product of industry (especially mining), arsenic is also a serious Canadian concern. While reducing human exposure should be a major priority, evidence suggests that humans are susceptible to arsenic-induced disease for decades following cessation of chronic exposure. Furthermore, in many regions, removing exposure is not economically feasible. Thus, strategies for the treatment and prevention of As-induced disease are necessary. Selenium is an essential trace element which is toxic in excess. Selenium reduces the toxic effects of arsenic in lab animals by increasing its elimination from the body. Low blood selenium levels in humans chronically exposed to arsenic have been associated with increased risk for arsenic-induced disease. Clinical trials for testing the ability of selenium tablets or selenium-enriched diets to prevent arsenic-induced disease have been initiated in arsenic-endemic regions. The study of how selenium modifies the toxicity of arsenic in human tissues has been largely ignored, despite marked differences in arsenic detoxification between humans and lab animals. Furthermore, selenium comes in many different chemical forms and the best form for supplementation and prevention of arsenic-induced disease is not known. The overall goal of this research is to understand the influence of different forms of selenium on arsenic metabolism and transport in human liver and red blood cells. Ultimately, this information is critical for optimizing human selenium supplementation and for the prevention and treatment of arsenic-induced disease.