Project Summary (2000-2005)

The biochemical fate of inorganic arsenate and arsenite and their biotransformants are the major interest of this project. Elucidation of the fate of inorganic arsenic in mammals would be expected to lead to a better understanding of the mechanisms of chronic inorganic arsenic poisoning. Inorganic arsenic in the drinking water of millions of people has become a problem of global proportions. Populations are drinking water containing levels of arsenic that far exceed the maximum contamination levels established by World Health Organization and the United States EPA. Arsenic is a carcinogen for humans. Yet, how the human and other mammals process and detoxify the toxic inorganic forms of arsenic is still beset by conflicting reports, ambiguities and unknowns. This laboratory is studying the enzymes in the human body that modify the toxicity of arsenic species. Researchers are purifying these enzymes and studying their molecular mechanisms of action. Inhibitors of this process are being sought as a possible way to block conversion to any carcinogenic biotransformant. A compound of high concentration in the cell is glutathione and it is known to form complexes with arsenic species. Project investigators are studying these complexes to determine the role of glutathione in how arsenic species efflux the cell.