Chromosomal aberrations induced by 5-azacytidine combined with VP-16 (etoposide) in CHO-K1 and XRS-5 cell lines.

A P A Guimarães, F L Dias, R S Cardoso, S N Kronka, E T Sakamoto-Hojo
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引用次数: 5

Abstract

A cytogenetic study was carried out with 5-azacytidine (5-azaC) and etoposide (VP-16) in CHO-K1 and XRS-5 (mutant cells deficient for double-strand break rejoining) cell lines to verify the interaction effects of the drugs in terms of induction of chromosomal aberrations. 5-azaC is incorporated into DNA causing DNA hypomethylation, and VP-16 (inhibitor of topoisomerase II enzyme) is a potent clastogenic agent. Cells in exponential growth were treated with 5-azaC for 1 h, following incubation for 7 h, and posttreatment with VP16 for the last 3 h. In K1 cells, the combined treatments induced a significant reduction in the aberrations induced in the X and "A" (autosome) chromosomes, which are the main target for 5-azaC. However, in XRS-5 cells, the drug combination caused a significant increase in the aberrations induced in those chromosomes, but with a concomitant reduction in the randomly induced-aberrations. In addition, each cell line presented characteristic cell cycle kinetics; while the combined treatment induced an S-arrest in K1 cells, alterations in cell cycle progression were not found for XRS-5, although each drug alone caused a G2-arrest. The different cell responses presented by the cell lines may be explained on the basis of the evidence that alterations in chromatin structure caused by 5-aza-C probably occur to a different extent in K1 and XRS-5 cells, since the mutant cells present a typical hyper-condensed chromosome structure (especially the X- and "A" chromosomes), but, alternatively, 5-aza-C could induce reactivation of DNA repair genes in XRS-5 cells.

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5-氮扎胞苷联合VP-16(依托泊苷)诱导CHO-K1和XRS-5细胞系染色体畸变。
用5-氮杂胞苷(5-azaC)和依托opo苷(VP-16)在CHO-K1和XRS-5(缺乏双链断裂重新连接的突变细胞)细胞系中进行细胞遗传学研究,以验证药物在诱导染色体畸变方面的相互作用。5-azaC被并入DNA导致DNA低甲基化,VP-16(拓扑异构酶II酶抑制剂)是一种有效的致裂剂。指数生长的细胞用5-azaC处理1小时,然后孵育7小时,最后用VP16处理3小时。在K1细胞中,联合处理显著减少了X和a(常染色体)的畸变,这是5-azaC的主要靶点。然而,在XRS-5细胞中,药物组合导致这些染色体中诱导的畸变显著增加,但同时随机诱导的畸变减少。此外,每个细胞系都表现出特有的细胞周期动力学;虽然联合治疗诱导K1细胞s -阻滞,但XRS-5细胞周期进程未发现改变,尽管每种药物单独引起g2 -阻滞。细胞系表现出的不同细胞反应可能是基于以下证据,即K1和XRS-5细胞中5-aza-C引起的染色质结构改变可能在不同程度上发生,因为突变细胞呈现典型的超浓缩染色体结构(特别是X-和“a”染色体),但另一方面,5-aza-C可以诱导XRS-5细胞中DNA修复基因的再激活。
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