Uridine as the only alternative to pyrimidine de novo synthesis in rat T lymphocytes

Abstract

Concanavalin A-induced proliferation of rat T-lymphocytes is completely inhibited by 10 −5 M pyrazofurin, a potent inhibitor of pyrimidine de novo synthesis, as judged by cell viability and [ 3H]thymidine incorporation. Proliferation is completely restored by 5 × 10 −5 M uridine. Cytidine, deoxycytidine, deoxyuridine and thymidine 10 × 10 −5 M each, fail to re-establish proliferation but produce an isotropic dilution of [ 3H]thymidine uptake in DNA. Bases (cytosine, uracil and thymine) neither restore proliferation nor induce isotopic dilution. The unexpected inability of cytidine to reverse de novo pyrimidine synthesis inhibition suggests a lack of cytidine deaminase activity in rat T-lymphocytes. This is confirmed by a direct sensitive radioisotopic assay (<0.001 nmol.min −1.10 −6 cells).