Small polydispersed circular DNA (spcDNA) in human cells: Association with genomic instability
Small polydispersed circular DNA (spcDNA) in human cells: Association with genomic instability
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DOI：
10.1038/sj.onc.1200917
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发表时间：
1997-02-27
期刊：
影响因子：
8
通讯作者：
Lavi, S
中科院分区：
文献类型：
--
作者：
Cohen, S;Regev, A;Lavi, S
小多分散环状DNA（spcDNA）被认为与遗传不稳定的细胞有关。然而，到目前为止，定性和定量研究一直受到限制，由于缺乏有效的检测和分析方法。我们开发了一个二维（2-D）中性-中性凝胶电泳分析的鉴定，表征和定量的spcDNA。使用这种方法，我们建立了spcDNA的遗传和诱导的基因组不稳定性在人类细胞中，在体外和体内的关系。在遗传不稳定的细胞和组织中发现spcDNA的量增加。在肿瘤细胞系（HeLa）和肿瘤组织（结肠癌）以及来源于患有基因组不稳定性疾病Fanconi贫血的患者的成纤维细胞中检测到spcDNA。我们未能在遗传稳定的正常人成纤维细胞中检测到spcDNA。然而，在用起始致癌物MNNG处理后，观察到spcDNA的诱导。根据线粒体DNA（mtDNA）标准品定量spcDNA的水平。根据这些发现，我们讨论了spcDNA作为标记和基因组不稳定性的增强子的可能作用。
Small Polydispersed Circular DNA (spcDNA) was suggested to be associated with genetically unstable cells. However, until now, qualitative and quantitative research has been limited due to the lack of efficient methods for detection and analysis. We developed a two-dimensional (2-D) neutral-neutral gel electrophoresis assay for the identification, characterisation and quantitation of spcDNA. Using this method, we established the relation of spcDNA to genetic and induced genomic instability in human cells, both in vitro and in vivo. Enhanced amounts of spcDNA were found in genetically unstable cells and tissues. spcDNA was detected in a tumor cell-line (HeLa) and in tumor tissue (colon carcinoma) as well as in fibroblasts derived from patients suffering from the genomic instability disease, Fanconi's Anemia. We failed to detect spcDNA in the genetically stable normal human fibroblasts. However, following treatment with the initiating carcinogen MNNG, an induction of spcDNA was observed. The level of spcDNA was quantified according to mitochondrial DNA (mtDNA) standards. In light of these findings, we discuss the possible role of spcDNA as a marker and an enhancer of genomic instability.