Gene expression profiles in mouse liver cells after exposure to different types of radiation
Gene expression profiles in mouse liver cells after exposure to different types of radiation
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DOI：
10.1269/jrr.07078
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发表时间：
2008-01-01
影响因子：
2
通讯作者：
Fukumoto, Manabu
中科院分区：
文献类型：
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作者：
Roudkenar, Mehryar Habibi;Li, Li;Fukumoto, Manabu
肝脏是由内照射引起的辐射致癌的靶器官之一。为了阐明包括Thorotrast在内的辐射诱导肝癌，我们提出了一种新的方法来研究内部暴露于α粒子的体内效应。采用硼中子俘获法，在体内分别照射小鼠肝脏库普弗细胞和内皮细胞，通过寡核苷酸芯片分析基因转录的变化。差异表达定义为与未辐照对照相比，上调表达量大于3倍，下调表达量小于1/3。在检测的6050个基因中，有68个与未辐照小鼠相比表现出差异表达。实时聚合酶链反应验证了微阵列分析的结果。暴露于x射线粒子和伽马射线中会产生不同的基因表达改变模式。基因表达谱显示，肝脏处于炎症状态，其特征是阳性急性期蛋白基因上调，而与暴露于辐射的靶细胞无关。与化学和生物肝毒物相比，辐射暴露的特点是金属硫蛋白I和血红素的诱导以及细胞色素p450的抑制。抗炎治疗有助于预防和保护放射性肝损伤。
The liver is one of the target organs of radiation-induced cancers by internal exposures. In order to elucidate radiation-induced liver cancers including Thorotrast, we present a new approach to investigate in vivo effects of internal exposure to alpha-particles. Adopting boron neutron capture, we separately irradiated Kupffer cells and endothelial cells in mouse liver in vivo and analyzed the changes in gene transcriptions by an oligonucleotide microarray. Differential expression was defined as more than 3-fold for up-regulation and less than 1/3 for under-regulation, compared with non-irradiated controls. Of 6,050 genes examined, 68 showed differential expression compared with non-irradiated mice. Real-time polymerase chain reaction validated the results of the microarray analysis. Exposure to (x-particles and gamma-rays produced different patterns of altered gene expression. Gene expression profiles revealed that the liver was in an inflammatory state characterized by up-regulation of positive acute phase protein genes, irrespective of the target cells exposed to radiation. In comparison with chemical and biological hepatotoxicants, inductions of Metallothionein I and Hemopexin, and suppressions of cytochrome P450s are characteristic of radiation exposure. Anti-inflammatory treatment could be helpful for the prevention and protection of radiation-induced hepatic injury.