Inhibition of thymidine and basic amino acid metabolism in P1798 lymphosarcoma by L-asparaginase.

In vivo metabolism of lysine and arginine is markedly inhibited (p < 0.025) in P1798 lymphosarcoma within 1 hr after intraperitoneal injection of 1 unit of Escherichia coli L-asparaginase II. Two hr after treatment, there is substan tial inhibition of thymidine transport but no effect on incorporation of thymidine. None of these effects were observed in the L-asparaginase-resistant subline of the tumor. The inhibition of lysine transport and incorporation was maximal (40%) 1hr after treatment was given, while the effect on arginine metabolism increased with time. Since the course of inhibition of transport and incorporation almost coincide, the initial effect is probably on the transport. Alterations of the plasma membranes of the tumor are suggested, but it is not known whether such lesions are caused by a direct action of L-asparaginase on the cells or are the result of a general systemic effect in the animal.