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 let hal 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 com pound 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 th e mammalian metabolism of arsenite, selenite, and sulfur. It provides a mol ecular basis for the antagonistic interaction between these metalloid compo unds, and a potential explanation of the association of cancer with prolong ed intake of inorganic arsenic in humans.