The homocysteine derivative, S-methylthio-DL-homocysteine (SMETH) was synthesized and found to be cytotoxic to L1210 cells in culture. Its cytotoxicity was increased in the presence of leucine, which interferes with glutamine utilization as an energy source. A working hypothesis is presented which describes the interaction of homocysteine, formed by intracellular disulfide reduction of SMETH, with adenosine, formed by intracellular dephosphorylation of ATP. This mechanism may be applicable for development of chemotherapy of slowly growing or latent tumors.
