Correlations of dihydropyrimidine dehydrogenase, thymidine phosphorylase and thymidine kinase activities in strongly and weakly malignant cultured murine neuroblastoma cells

Abstract

The C‐1300 neuroblastoma tumor which arises spontaneously in the A/J mouse has been maintained in this mouse strain. Two different cell populations have been recognized in cultured C‐1300 mouse neuroblastoma (MNB): (1) round, “neuroblast‐like” cells, growing in suspension (poorly attached), that have a highly malignant behavior when injected into the A/J mouse (T1 cells); and (2) flat, “epithelioid” cells that attach well to surfaces and show low malignancy towards the inoculated animals (T2 cells). The specific activities of the pyrimidine metabolizing enzymes thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD) and thymidine kinase (TK) were examined in both MNB cell lines by a new radiochromatographic method. Enzymatic activities of TP and DPD in the cytosols of T2 (weakly malignant) cells were up to 15 times higher than those of T1 (strongly malignant) cells, whereas the mean TP/DPD activity ratio was 16 in either cell line. TP and DPD activity levels increased with time of growth in culture in T2 cells while no such increase was seen in the T1 cells. Maximal TK activity was similar in both cell lines but dropped more rapidly in the T2 cells as cell densities increased. The enzymatic activity levels of TP and DPD but not of TK correlated inversely with neoplastic expression of MNB cells. The observed patterns of pyrimidine metabolizing enzymes in MNB cells could result in an increased thymidine pool in T1 cells whenever TK activity is suppressed, whereas such conditions would favor the generation of thymine in the T2 cells.