The L-arginine dependent effector mechanism is induced in murine adenocarcinoma cells by culture supernatant from cytotoxic 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, nitrate, and nitrate synthesis from L-arginine by EMT-6 cells. Protein synthesis is required for activation of this effector mechanism. Once the effector pathway is induced in EMT-6 cells in the presence of amino acids, L-arginine is the only amino acid required for its function. Arginase inhibits 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.