Differential metabolism of thymidine in human lymphoid and melanoma cells in vitro

Four potentially key enzyme activities of thymidine metabolism were examined in 4 human cell lines differing widely in sensitivity to thymidine. Two melanoma cells showed intermediate sensitivity to thymidine compared with highly sensitive T-lymphoid cells and relatively resistant B-lymphoid cells. Thymidine kinase activity varied modestly among the 4 cell lines; while thymidine phosphorylase activity was markedly higher in extracts of both melanoma cells and B-cells. dTMP phosphatase activity was markedly higher in extracts of melanoma cells compared to both T- and B-cells. The rate of dTTP degradation in intact cells was appreciably higher in the B-cells compared to both melanoma cells and T-cells. It is possible that elevated levels of thymidine phosphorylase activity account for decreased sensitivity to thymidine, and that enhanced dTTP catabolic activity imparts additional resistance.