抗肿瘤药物5-氮杂胞苷处理后培养的CHO细胞中DNA拓扑异构酶水平升高。

Cytobios Pub Date : 1999-01-01
J Piñero, M López-Baena, T Ortiz, S Mateos, F Cortés
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引用次数: 0

摘要

用胞苷类似物5-氮杂胞苷(5-azaC)处理培养的中国仓鼠卵巢(CHO)细胞,结果与先前在其他初级或已建立的哺乳动物细胞系中进行的研究结果一致,导致染色体广泛去致密化,并将正常晚复制的异染色质的复制时间转移到更早的复制时间。DNA拓扑异构酶(主要是topo I)参与转录,据报道5-azaC的低甲基化作用导致沉默基因的表达。这种转录的增加是否与topo I和topo II水平的增加以及拓扑异构酶活性的增强相平行,已经在这项工作中进行了研究。结果似乎表明,拓扑异构酶的相对数量和它们的活性在经过长时间的胞苷类似物治疗后比在未治疗的对照组中观察到的要增强。这些观察结果可能对抗肿瘤治疗具有重要意义。
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Increased levels of DNA topoisomerases in cultured CHO cells treated with the antitumour drug 5-azacytidine.

Cultured Chinese hamster ovary (CHO) cells were treated with the cytidine analogue 5-azacytidine (5-azaC) which, in good agreement with results previously described from studies carried out in other primary or established mammalian cell lines, resulted in extensive chromosome decondensation and a shift in the time of replication of normally late-replicating heterochromatin to earlier replication. DNA topoisomerases (mainly topo I) have been involved in transcription, and the hypomethylating effect of 5-azaC reportedly results in the expression of silenced genes. Whether such an increase in transcription is paralleled by increased levels of both topo I and topo II, as well as by an enhancement in the topoisomerase activities, has been investigated in this work. The results seem to suggest that both the relative amount of topoisomerases and their activities are enhanced after a protracted treatment with the cytidine analogue over those observed in untreated controls. These observations could be significant for antitumour therapy.

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