Effects of Sulfur-containing Hydantoin Derivatives on Metabolism of Ehrlich Ascites Carcinoma

A number of structurally related hydantoins has been examined for their effects on the metabolic activities of Ehrlieh aseites carcinoma cells. 5-Ethylsulfinylmethylhydantoin [ESH] was a potent inhibitor of such activities. 5-Ethylsulfonylmethylhydantoin had less activity, and the other hydantoins tested were without effect. ESH was also a potent inhibitor of metabolism in Salk "altered" monkey heart cells cultured in vitro but was less effective with chick embryo. Amino acid incorporation into the proteins of Ehrlieh ascites carcinoma cells was the most sensitive to ESH of all metabolic activities examined, appreciable inhibition occurring at a concentration of 0.~ mM under aerobic conditions. The presence of mouse liver slices diminished the inhibitory activity of ESH on amino acid incorporation in Ehrlieh aseites cells, pointing to the breakdown of the hydantoin in the presence of liver. The presence of glutathione reversed the inhibitory action of ESt I on amino acid incorporation into the proteins of Ehrlieh ascites cells, indicating that the hydantoin may act by inactivation of enzymic thiol groups.