Abstract
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.
Highlights
Summary.- 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
The extracts of liver containing arginase or purified beef liver arginase were incubated at 38°C with various cells in culture; up to 100 % cell death was observed after 20 h with the usual number of cells 5 x 105
Similar results were obtained with L5178Y and L1210 mouse lymphoma cells, with the IRC rat monocytic leukaemia and the rat astrocytoma (Table I)
Summary
Summary.- 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 with arginine and partially with arginino-succinic acid, citrulline and ornithine. The concentration of arginine was critical; at 8 ,umol/l the cells remained viable and reversible inhibition could be shown; below this level cells died. In contrast to reports in the literature of reversible inhibition, arginase produced severe damage to all tumour cells examined. The incorporation of labelled substrates, and the cell viability were examined at various concentrations of arginine to ascertain the nature of the damage. A preliminary account of this work has been reported (Burton, 1969)
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