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作 者:陈小朋[1] 袁守军[2] 丁林茂[2] 傅学琦[1] 徐兰平[2] 田增月[2]
机构地区:[1]吉林大学生命科学学院,吉林长春130023 [2]军事医学科学院放射医学研究所药理毒理研究室,北京100850
出 处:《中国药理学与毒理学杂志》2003年第1期44-50,共7页Chinese Journal of Pharmacology and Toxicology
摘 要:目的 从整个细胞基因组表达变化的角度 ,研究沙利度胺 (Tha)对基因表达谱的影响 ,揭示发育毒性药物的致畸机制。方法 用载有 8192条基因的DNA微矩阵芯片 ,检测在 11.6μmol·L- 1的Tha作用4 2h后 ,HepG2细胞基因表达谱的变化。结果有 19条基因的表达有明显变化 ,其中 17条基因表达下调 ,2条基因表达上调。下调基因中有多条为转录调控和胚胎发育相关基因 ,上调的基因中有DNA修复相关基因和线粒体功能相关的基因。结论 Tha能影响若干基因转录和胚胎发育基因的表达 ,可能与其发育毒性机制相关 。AIM To study model cells-HepG2 cell′s responses to thalidomide(Tha) and reveal the possible mechanism of its teratogenesis through genomic-scale gene expression analysis. METHODS the effects of gene expression profiles of HepG2 cells exposed to Tha(11.6 μmol·L -1) 42 h were investigated with DNA microarray representing 8192 human genes. RESULTS There were nineteen genes whose expression had obvious change, seventeen of which were down-regulated, two up-regulated. Interestingly, a number of genes down-regulated by Tha were involved in modulation of transcription and embryo development, and the up-regulated genes were related to DNA repair ability and the function of mitochondria. CONCLUSION Tha can disturb genes expression of transcription and embryo development, which may be relate to its development toxicity mechanism.
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