Correlations of dihydropyrimidine dehydrogenase, thymidine phosphorylase and thymidine kinase activities in strongly and weakly malignant cultured murine neuroblastoma cells
Correlations of dihydropyrimidine dehydrogenase, thymidine phosphorylase and thymidine kinase activities in strongly and weakly malignant cultured murine neuroblastoma cells
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强、弱恶性培养的鼠神经母细胞瘤细胞中二氢嘧啶脱氢酶、胸苷磷酸化酶和胸苷激酶活性的相关性
DOI：
10.1002/ijc.2910430528
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发表时间：
1989
影响因子：
6.4
通讯作者：
M. Tuchman
中科院分区：
文献类型：
--
作者：
C. Williams;M. Tuchman
在A/J小鼠中自发产生的C-1300神经母细胞瘤肿瘤在该小鼠品系中得以维持。在培养的C-1300小鼠神经母细胞瘤（MNB）中发现了两种不同的细胞群：（1）圆形的“神经母细胞样”细胞，在悬浮液中生长（附着不良），当注射到A/J小鼠中时具有高度恶性行为（T1细胞）;和（2）扁平的“上皮样”细胞，良好附着于表面，对接种的动物显示出低恶性（T2细胞）。用放射色谱法测定了两种MNB细胞系中嘧啶代谢酶胸苷磷酸化酶（TP）、二氢嘧啶脱氢酶（DPD）和胸苷激酶（TK）的活性。TP和DPD在T2（弱恶性）细胞的细胞质中的酶活性比T1（强恶性）细胞的酶活性高15倍，而在任一细胞系中的平均TP/DPD活性比为16。TP和DPD活性水平随着T2细胞培养中生长时间的增加而增加，而在T1细胞中没有看到这种增加。最大TK活性在两种细胞系中相似，但随着细胞密度的增加，T2细胞中的TK活性下降更快。TP和DPD的酶活性水平与MNB细胞的肿瘤表达呈负相关，但TK的酶活性水平与MNB细胞的肿瘤表达无关。在MNB细胞中观察到的嘧啶代谢酶模式可能导致T1细胞中胸苷池增加，而这种条件下，TK活性受到抑制时，有利于T2细胞中胸腺嘧啶的生成。
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.