Different mutation patterns of mitochondrial DNA displacement-loop in hepatocellular carcinomas induced by N-nitrosodiethylamine and a choline-deficient L-amino acid-defined diet in rats
Different mutation patterns of mitochondrial DNA displacement-loop in hepatocellular carcinomas induced by N-nitrosodiethylamine and a choline-deficient L-amino acid-defined diet in rats
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DOI：
10.1016/j.bbrc.2007.07.175
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发表时间：
2007-10-12
影响因子：
3.1
通讯作者：
Tsujiuchi, Toshifumi
中科院分区：
文献类型：
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作者：
Onishi, Mariko;Sokuza, Yui;Tsujiuchi, Toshifumi
通过对线粒体DNA(MtDNA)置换环(D-loop)突变的研究，阐明外源性和内源性大鼠肝癌发生的不同变化。我们用N-亚硝基二乙胺(DEN)和胆碱缺乏的L氨基酸饲料诱发大鼠肝细胞癌。从DEN诱导的10个肝癌细胞和CDAA饮食诱导的10个肝癌细胞中提取DNA。采用聚合酶链式反应-单链构象多态分析和核苷酸测序的方法检测线粒体DNA D-loop突变。在DEN诱发的10例肝癌中，有5例(50%)检测到突变。5个突变中有4个是位于15707、15717、15930和16087位的G/C到A/T转换，以及1个位于15559位的T/A到C/G转换。相比之下，在CDAA饮食诱导的10例肝癌中未发现突变。这些结果表明，在DEN诱导的大鼠肝癌细胞中，mtDNA D-loop发生突变，而CDAA饮食诱导的大鼠肝细胞中mtDNA D-loop突变，提示mtDNA D-loop是外源性大鼠肝癌发生的靶点。(C)2007 Elsevier Inc.保留所有权利。
Mutations of the mitochondria DNA (mtDNA) displacement loop (D-loop) were investigated to clarify different changes of exogenous and endogenous liver carcinogenesis in rats. We induced hepatocellular carcinomas (HCCs) in rats with N-nitrosodiethylamine (DEN) and a choline-deficient L-amino acid-defined (CDAA) diet. DNAs were extracted from 10 HCCs induced by DEN and 10 HCCs induced by the CDAA diet. To identify mutations in mtDNA D-loop, polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis, followed by nucleotide sequencing, was performed. Mutations were detected in 5 out of 10 HCCs (50%) induced by DEN. Four out of 5 mutations were G/C to A/T transitions at positions 15707, 15717, 15930, and 16087, and one T/A to C/G transition at position 15559. By contrast, no mutations were found in 10 HCCs induced by the CDAA diet. These results demonstrated that mutations in mtDNA D-loop occur in rat HCCs induced by DEN but not by the CDAA diet, suggesting that mtDNA D-loop is a target of exogenous liver carcinogenesis in rats. (C) 2007 Elsevier Inc. All rights reserved.