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镉暴露大鼠三个不同常见脆性位点(D6mit3、D9mit2 和 D15Mgh1)处微卫星不稳定性。

Microsatellite instability at three microsatellite loci (D6mit3, D9mit2 and D15Mgh1) located in different common fragile sites of rats exposed to cadmium.

机构信息

Zoology Department, Cairo University, Egypt.

出版信息

Mutat Res. 2010 Feb;696(2):160-6. doi: 10.1016/j.mrgentox.2010.01.007. Epub 2010 Jan 25.

DOI:10.1016/j.mrgentox.2010.01.007
PMID:20100592
Abstract

Cadmium (Cd) is a non-essential element and is a widespread environmental pollutant. Exposure to cadmium can result in cytotoxic, carcinogenic and mutagenic effects. Mutagenesis is an indicative of genetic instability and can be assayed using microsatellites instability. The aim of the present study is to investigate; based on the rat model, the effects of oral acute (single 8.8mg/kg BW, 1/10 LD(50)) and sub-chronic (2.93mg/kg BW, 1/30 LD(50), for 4 weeks) doses of cadmium chloride on microsatellite instability at D6mit3, D9mit2 and D15Mgh1 loci, which are located in three different common fragile sites (6q21, 9q32-q33 and 15p14, respectively), within rat genome. In the acute study, no microsatellite instability (MSI) was observed in all the three tested loci (D6mit3, D9mit2 and D15Mgh1). In the sub-chronic study, the MSI were observed in the three studied loci and was in the form of deletion of 2-3bp or addition of 3-6bp. These finding may indicate the sensitivity of microsatellite sequences located at the fragile sites and the sensitivity of the simple sequence repeats (SSRs) assay for the detection of small variations in DNA sequence. However, additional chronic toxicological trials are needed in order to assess genotoxic effects of chronic exposure to Cd.

摘要

镉(Cd)是非必需元素,也是一种广泛存在的环境污染物。接触镉会导致细胞毒性、致癌和致突变作用。突变是遗传不稳定性的指标,可以使用微卫星不稳定性来检测。本研究的目的是基于大鼠模型,研究氯化镉的急性(单次 8.8mg/kg BW,1/10 LD(50))和亚慢性(2.93mg/kg BW,1/30 LD(50),4 周)剂量对 D6mit3、D9mit2 和 D15Mgh1 微卫星不稳定性的影响,这些基因位于大鼠基因组中的三个不同的常见脆弱位点(分别为 6q21、9q32-q33 和 15p14)。在急性研究中,在所有三个测试的基因座(D6mit3、D9mit2 和 D15Mgh1)中均未观察到微卫星不稳定性(MSI)。在亚慢性研究中,三个研究基因座均观察到 MSI,表现为 2-3bp 的缺失或 3-6bp 的添加。这些发现可能表明位于脆弱位点的微卫星序列的敏感性和简单重复序列(SSRs)分析对 DNA 序列微小变化的检测敏感性。然而,需要进行额外的慢性毒性试验,以评估慢性接触 Cd 的遗传毒性作用。

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