The effects of phenylalanine ammonia-lyase on leukemic lymphocytes in vitro.

Phenylalanine ammonia-lyase, which irreversibly deaminates phenylalanine and tyrosine, markedly inhibited the growth of human leukemic and murine L5178Y lymphoblasts in vitro but had a negligible effect on resting (nondividing) normal lymphocytes. These studies also demonstrated that phenylalanine ammonia-lyase inhibited DNA synthesis in leukemic cells at least as effectively as did asparaginase. Furthermore, neither cinnamic acid, coumaric acid and ammonia, the products of phenylalanine and tyrosine deamination, nor inactivated phenylalanine ammonia-lyase affected the growth of the lymphoblasts. These results suggest that phenylalanine ammonia-lyase inhibited cell division by depriving these rapidly dividing cells of phenylalanine and tyrosine.