Cihák A, Seifertová M, Riches P
Cancer Res. 1976 Jan;36(1):37-42.
The administration of 5-azacytidine to rats resulted in enhancement of thymidine incorporation into liver DNA. Repeated doses of the drug caused a greater than 10-fold increase of thymidine incorporation. In 5-azacytidine-treated intact rats no changes in the activity of thymidine and thymidylate kinases were observed, whereas a marked depression of thymidine phosphorylase activity occurred. In intact animals the mitotic activity in the drug-treated livers changed slightly; however, 5-azacytidine administration before partial hepatectomy resulted in a dramatic increase of mitotic activity in 24-hr regenerating livers. In this case the observed increase in incorporation of thymidine was paralleled both by increased activity of thymidine and thymidylate kinases and by a decline in thymidine phosphorylase activity. The higher incorporation of radioactivity into liver DNA in intact rats pretreated with the drug can be accounted for, at least partially, by the lower cellular degradation of the injected radioactive thymidine used for labeling. In addition, alterations in the labeling and in the mitotic activity of hepatocytes and nonparenchymal cells caused by 5-azacytidine should be taken into consideration.
给大鼠施用5-氮杂胞苷会导致胸腺嘧啶核苷掺入肝脏DNA的量增加。重复给药会使胸腺嘧啶核苷掺入量增加10倍以上。在经5-氮杂胞苷处理的完整大鼠中，未观察到胸腺嘧啶核苷激酶和胸苷酸激酶的活性发生变化，而胸腺嘧啶核苷磷酸化酶的活性则显著降低。在完整动物中，药物处理的肝脏中的有丝分裂活性略有变化；然而，在部分肝切除术前施用5-氮杂胞苷会导致24小时再生肝脏中的有丝分裂活性显著增加。在这种情况下，观察到的胸腺嘧啶核苷掺入增加与胸腺嘧啶核苷激酶和胸苷酸激酶活性增加以及胸腺嘧啶核苷磷酸化酶活性下降同时出现。在用该药物预处理的完整大鼠中，肝脏DNA中放射性掺入量较高，这至少部分可以归因于用于标记的注射放射性胸腺嘧啶核苷的细胞降解较低。此外，还应考虑5-氮杂胞苷引起的肝细胞和非实质细胞标记及有丝分裂活性的改变。
