Radiation-induced gene expression profile of human cells deficient in 8-hydroxy-2′-deoxyguanine glycosylase
Radiation-induced gene expression profile of human cells deficient in 8-hydroxy-2′-deoxyguanine glycosylase
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DOI：
10.1002/ijc.21392
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发表时间：
2006-03-01
影响因子：
6.4
通讯作者：
Chaudhry, MA
中科院分区：
文献类型：
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作者：
Chaudhry, MA
人OGG1基因编码一种DNA糖基酶，参与氧化损伤DNA中8-羟基-2‘-脱氧鸟嘌呤(8-OH-DG)的碱基切除修复。在缺乏这种活性的情况下，细胞内8-OH-DG水平会累积，对细胞可能是有害的。为了在特定的DNA修复缺陷背景下评估8-氧鸟嘌呤糖基酶(OGG1)在细胞防御机制中的作用，我们开始研究电离辐射后OGG1缺陷的人KG-I细胞中碱基切除修复基因和其他不参与碱基切除途径的细胞基因的表达模式。由于Arg229Gln的纯合突变，Kg-I细胞失去了OGG1活性。观察照射后4、8、12、24小时细胞基因表达的变化。利用DNA微阵列技术对大规模基因表达谱进行评估。基因表达分析鉴定了一些电离辐射响应基因，其中包括几个新基因。辐射诱导的基因诱导或抑制有两个高峰：一个在8小时，另一个在24小时。总体而言，下调基因的数量高于上调基因的数量。在辐射后8小时，下调基因的数量最多。确定了与细胞、生理、发育和细胞外过程相对应的基因。辐射诱导基因数量最多的是信号转导类基因，其次是转录和应激反应基因。微阵列基因表达数据通过相对定量RT-PCR进行独立验证。令人惊讶的是，参与辐射诱导的DNA损伤的碱基切除修复的基因中没有一个显示出变化的表达。(C)2005年Wiley-Liss，Inc.
The human OGG1 gene encodes a DNA glycosylase that is involved in the base excision repair of 8-hydroxy-2'-deoxyguanine (8-OH-dG) from oxidatively damaged DNA. Cellular 8-OH-dG levels accumulate in the absence of this activity and could be deleterious for the cell. To assess the role of 8-oxoguanine glycosylase (OGG1) in the cellular defense mechanism in a specific DNA repair defect background, we set out to determine the expression pattern of base excision repair genes and other cellular genes not involved in the base excision pathway in OGG1-deficient human KG-I cells after ionizing radiation exposure. KG-I cells have lost OGG1 activity due to a homozygous mutation of Arg229Gln. Gene expression alterations were monitored at 4, 8, 12 and 24 hr in 2 Gy irradiated cells. Large-scale gene expression profiling was assessed with DNA microarray technology. Gene expression analysis identified a number of ionizing radiation-responsive genes, including several novel genes. There were 2 peaks of radiation-induced gene induction or repression: one at 8 hr and the other at 24 hr. Overall the number of downregulated genes was higher than the number of upregulated genes. The highest number of downregulated genes was at 8 hr postirradiation. Genes corresponding to cellular, physiologic, developmental and extracellular processes were identified. The highest number of radiation-induced genes belonged to the signal transduction category, followed by genes involved in transcription and response to stress. Microarray gene expression data were independently validated by relative quantitative RT-PCR. Surprisingly, none of the genes involved in the base excision repair of radiation-induced DNA damage showed altered expression. (c) 2005 Wiley-Liss, Inc.