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.
D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D008545:Melanoma / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism* / Q000494:pharmacology; D013937:Thymidine Kinase / Q000378:metabolism; D013939:Thymidine Phosphorylase / Q000378:metabolism; D013942:Thymine Nucleotides / Q000378:metabolism; D014543:Uridine Phosphorylase / Q000378:metabolism
D013942:Thymine Nucleotides; D014543:Uridine Phosphorylase; D013939:Thymidine Phosphorylase; D013937:Thymidine Kinase; D010744:Phosphoric Monoester Hydrolases; C024157:thymidine 5'-triphosphate; D013936:Thymidine