The Effects of Arginine Deficiency on Lymphoma Cells

When L5178Y and L1210 mouse lymphosarcoma cells were incubated with rat or beef liver arginase there was up to 100% cell destruction in 24 hours. This was reversed specifically with arginine and partially with arginino-succinic acid, citrulline and ornithine. The concentration of arginine was critical; at 8 μmol/l the cells remained viable and reversible inhibition could be shown; below this level cells died. L5178Y cells were grown in medium containing from 0 to 80 μmol/l arginine for 24 hours then transferred to fresh medium for 24 hours. Viable cell counts and mitotic indices were determined, and cells were pulsed with (3)H-thymidine, (3)H-uridine, (14)C-leucine and (14)C-arginine at various times. Thymidine uptake was affected most and preceded parallel changes in viable cell numbers. It was concluded that arginine is required by these cells even in a "resting" state and despite some evidence for their capacity to utilize precursors, the tumour cells underwent rapid and extensive destruction when available arginine was severely depleted.