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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.
Amber et al. (Mon,) studied this question.