Differential arginine dependence and the selective cytotoxic effects of activated macrophages for malignant cells in vitro.

Normal and neoplastic cells from 4 species (man, rat, mouse and hamster) were examined for their dependence on exogenous L-arginine in tissue culture. The malignant cells required a higher concentration of L-arginine in the medium than their normal counterparts (with similar doubling times) to maintain optimal proliferation. Complete arginine deprivation resulted in equal growth inhibition of normal and malignant cells, but more rapid cytolysis of the malignant cell. Deprivation of L-arginine, followed 24 h later by rescue with L-arginine, allowed normal cells to proliferate, but the reproductive capacity of the malignant cells was irreversibly impaired. Since the cytotoxic activity of LPS-activated macrophages was associated with the release of arginase and was abrogated by excess L-arginine, it is suggested that the biological basis for the selective effects of such macrophages may reside in the L-arginine dependence of the target cells.