Uridine Fluxes in Healthy Proliferating T-Lymphocytes, Molt-3 T-ALL Cell-Line Cells and Differentiated Molt-3 Cells

Abstract

Knowledge of transformation associated differences in pyrimidine nucleotide metabolism of human leukemic cells, compared to healthy counterparts can be a rational basis for development of new antileukemic drugs. Peripheral blood cells of patients with acute lymphoblastic leukemia (ALL) contain increased amounts of guanine-, uracil- and cytosine- nucleotides and uridinediphosphate bound sugars with a changed composition. Moreover, the same deviations have also been found in the human ALL cell-line of T-lymphoblastic origin MOLT-3. Comparison of pyrimidine nucleotide synthesis from labeled precursors by MOLT-3 cells and growth-stimulated T-lymphocytes (TL’s), showed that CTP-synthetase ‘overactivity’ could cause the increase in cytosine nucleotides found in the malignant cell-line cells². Uridine fluxes by pulse-chase experiments in living cells with emphasis on CTP-synthetase activity and differences herein between MOLT-3 cells, TL’s and differentiated resting MOLT-3 cells, were performed to get a better insight in the fluxes and the role of CTP-synthetase.