A metabolic link between arsenite and selenite:: The seleno-bis(S-glutathionyl) arsinium ion

Among the most startling observations in mammalian toxicology is that a lethal dose of selenium can be overcome by an otherwise lethal dose of arsenic. We report the molecular basis of this antagonism. Using X-ray absorption spectroscopy we have identified a new arsenic-selenium compound in the bile of rabbits injected with aqueous selenite and arsenite solutions. This compound contains equimolar arsenic and selenium and exhibits X-ray absorption spectra which are essentially identical with those of a synthetic species in solution which we have identified spectroscopically as the seleno-bis(S-glutathionyl) arsinium ion. The in vivo detection of this compound links the mammalian metabolism of arsenite, selenite, and sulfur. It provides a molecular basis for the antagonistic interaction between these metalloid compounds, and a potential explanation of the association of cancer with prolonged intake of inorganic arsenic in humans.