THE L-ARGININE DEPENDENT EFFECTOR MECHANISM IS INDUCED IN MURINE ADENOCARCINOMA CELLS BY CULTURE SUPERNATANT FROM CYTO-TOXIC ACTIVATED MACROPHAGES

Culture medium conditioned by incubation with murine cytotoxic activated macrophages causes release of iron-55 label from viable murine EMT-6 tumor cells as well as inhibition of DNA replication and aconitase activity. These metabolic changes occur in parallel with L-citrulline, nitrite, and nitrate synthesis from L-arginine by EMT-6 cells. Protein synthesis is required for activation this effector mechanism. Once the effector pathway is induced by EMT-6 cells in the presence of amino acids, L-arginine is the only amino acid required for its function. Arginase inihibits the effector mechanism, which is additional evidence for its specific L-arginine requirement. The results show induction, in a non-macrophage cell line, of a novel effector pathway which, in addition to other effects, inhibits cellular proliferation.