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首页> 外文期刊>Journal of biochemical and molecular toxicology >Identification of phenobarbitone-modulated genes in mouse liver by differential display.
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Identification of phenobarbitone-modulated genes in mouse liver by differential display.

机译:差分显示鉴定小鼠肝脏苯溴醌调制基因。

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The molecular basis of how rodent nongenotoxic hepatocarcinogens such as phenobarbitone cause liver-tumor formation is poorly understood. An early effect of phenobarbitone exposure is to induce hepatocyte proliferation transiently, and there is evidence that this may be important for subsequent tumor development. In this investigation, we have used the differential display reverse transcriptase polymerase chain reaction technique to analyze differential gene expression in male C57B1/10J mouse liver during the mitogenic phase of the phenobarbitone response. Seventy-seven putative differentially expressed cDNAs were isolated by differential display, and 13 of them were subsequently confirmed as being differentially expressed (both increased and decreased by phenobarbitone). Seven of the cDNAs were homologous to known mouse or human genes (carboxylesterase, coagulation factor X, amine N-sulphotransferase, human protein disulphide isomerase-related protein, cytochrome c oxidase subunit IV, golgin-245, thioredoxin reductase, betaine-homocysteine methyl transferase) and the remainder were novel. The expression pattern of the sulphotransferase was further characterized, and in mouse liver it was found to be significantly induced by phenobarbitone and not by five other rodent nongenotoxic hepatocarcinogens. In summary, the technique has enabled the identification of previously uncharacterized genes whose expression patterns are differentially altered by phenobarbitone in the mouse liver.
机译:如何啮齿类毒性肝癌如苯丙酮导致肝脏肿瘤形成的分子基础。苯丙糖酮暴露的早期效果是瞬时诱导肝细胞增殖,并且有证据表明这对随后的肿瘤发育可能是重要的。在该研究中,我们使用了差异显示逆转录酶聚合酶链反应技术来分析苯巴西酮响应的促致态阶段的雄性C57B1 / 10J小鼠肝中的差动基因表达。通过差异显示分离七十七个推定的差异表达的CDNA,随后将其中13个被证实为差异表达(苯吡酮均增加和降低)。七个CDNA与已知的小鼠或人类基因同源(羧基酶,凝血因子X,胺N-砜异构酶相关蛋白,细胞色素C氧化酶亚基IV,Golgin-245,硫氧化嘧啶还原酶,甜菜碱 - 同型半胱氨酸甲基转移酶)和其余的是新颖的。硫转移酶的表达模式进一步表征,并且在小鼠肝脏中,发现由苯巴西酮显着诱导,而不是由其他5个其他啮齿动物的Nongenotoxic肝癌。总之,该技术使得先前没有表达模式的鉴定,其表达模式在小鼠肝脏中的苯吡酮差异地改变。

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