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Inhibitory Effect of L-Asparaginase in Lymphocyte Transformation Induced by Phytohemagglutinin

First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan

The effect of Escherichia coli L-asparaginase on phytohemagglutinin (PHA)-induced transformation of human lymphocytes was studied. Transformation was remarkably suppressed by the enzyme when it was added to the culture not later than 24 hr after its initiation. The effective concentration was more than 0.2 i.u./tube. Guinea pig serum and L-ß-aspartohydroxamic acid, an L-asparagine analog, have a suppressive effect on lymphocyte transformation in this system. PHA-treated lymphocytes became sensitive to L-asparaginase 12 hr after the culture was started, while no L-asparagine dependency was detected at any stage of the culture. An addition of L-asparagine or L-glutamine to the culture system treated with both PHA and L-asparaginase at zero time caused the partial recovery of thymidine-³H uptake.

Thus, it is concluded that one of the mechanisms inhibiting PHA lymphocyte transformation by L-asparaginase is due to the deprivation of exogenous L-asparagine and L-glutamine from the tissue culture medium.

Received 6/ 2/69. Accepted 8/ 6/69.