Potapova G I, Khramtsova S N, Dmitrieva L V, Shapot V S
Laboratory of Tumor Biochemistry, All-Union Cancer Research Center, Academy of Medical Sciences, Moscow, USSR.
Neoplasma. 1987;34(4):453-67.
In thymocytes of C3HA mice carrying the transplantable and ortoaminoazotoluene induced hepatomas at the time of their intense growth a drastic decrease in adenosine deaminase activity set in and 3-4-fold augmentation of intracellular concentration of dATP and dGTP, potential inhibitors of ribonucleoside diphosphate reductase was observed, leading to the reduction of the DNA synthesis. The latter event was evidenced by a suppressed 14C-thymidine incorporation into thymocytes DNA in vitro, decreased thymidine kinase activity, intracellular dTTP and depletion of dCTP pools. Only in the terminal period of hepatocarcinogenesis (12 months) a 4-fold increase in the corticosterone serum concentration was observed. As for the mice carrying transplantable 22a hepatoma, serum hormone levels augmented 4-fold as early as 24 h after tumor implantation and thereafter kept increased two fold. An elevated activity of terminal deoxynucleotidyl transferase in mouse thymocytes has been shown to be characteristic of the late periods of tumor growth reflecting the arrest of the immature cortical thymocyte differentiation. By the time hepatomas emerged in the course of hepatocarcinogenesis in spleen T and B lymphocytes a significant drop in the activity of adenosine deaminase (3-4-fold) and purine nucleoside phosphorylase (2-8-fold) was noted--the events directly correlated with the weakening of cell immune functions. The disorders described were accompanied by the accumulation of dGTP in spleen T lymphocytes, dATP in B lymphocytes and inhibition of DNA synthesis, predominantly in T lymphocytes. In the latter instance the pool of dCTP was found to be depleted. In spleen T and B lymphocytes of mice carrying solid 22a hepatoma when the peak of its growth was reached (day 5) the rate of DNA synthesis dropped. Later on (from day 8 to the animal death), however, in spite of the suppression of immune function and the decrease in adenosine deaminase activity a drastic stimulation of DNA synthesis in spleen T and B lymphocytes was observed. The increase in spleen T suppressor activity in the course of intense growth of the both types of hepatomas coincided in the time with the stimulation of the CTP-dependent thymidine kinase isoenzyme activity in total T lymphocyte population of the same organ.
在携带可移植的邻氨基偶氮甲苯诱导肝癌且处于强烈生长阶段的C3HA小鼠的胸腺细胞中，腺苷脱氨酶活性急剧下降，同时观察到dATP和dGTP（核糖核苷二磷酸还原酶的潜在抑制剂）的细胞内浓度增加了3至4倍，导致DNA合成减少。后者通过体外14C-胸腺嘧啶核苷掺入胸腺细胞DNA受到抑制、胸苷激酶活性降低、细胞内dTTP以及dCTP池耗竭得以证明。仅在肝癌发生的末期（12个月），观察到血清皮质酮浓度增加了4倍。至于携带可移植22a肝癌的小鼠，血清激素水平在肿瘤植入后24小时就增加了4倍，此后一直保持两倍的增长。已表明小鼠胸腺细胞中末端脱氧核苷酸转移酶活性升高是肿瘤生长后期的特征，反映了未成熟皮质胸腺细胞分化的停滞。在肝癌发生过程中脾脏T和B淋巴细胞出现肝癌时，腺苷脱氨酶（3至4倍）和嘌呤核苷磷酸化酶（2至8倍）的活性显著下降——这些事件与细胞免疫功能减弱直接相关。上述紊乱伴随着脾脏T淋巴细胞中dGTP、B淋巴细胞中dATP的积累以及DNA合成的抑制，主要是在T淋巴细胞中。在后一种情况下，发现dCTP池耗竭。在携带实体22a肝癌的小鼠脾脏T和B淋巴细胞中，当肿瘤生长达到峰值（第5天）时，DNA合成速率下降。然而，后来（从第8天到动物死亡），尽管免疫功能受到抑制且腺苷脱氨酶活性降低，但仍观察到脾脏T和B淋巴细胞中DNA合成受到强烈刺激。在两种类型肝癌的强烈生长过程中，脾脏T抑制活性的增加在时间上与同一器官的总T淋巴细胞群体中CTP依赖性胸苷激酶同工酶活性的刺激相吻合。
