Hot-spot mutations in the p53 gene of liver nodules induced in rats fed DL-ethionine with a methyl-deficient diet.
Hot-spot mutations in the p53 gene of liver nodules induced in rats fed DL-ethionine with a methyl-deficient diet.
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DOI：
10.1038/bjc.1997.329
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发表时间：
1997
影响因子：
8.8
通讯作者：
Lombardi B
中科院分区：
文献类型：
--
作者：
Tsujiuchi T;Yeleswarapu L;Konishi Y;Lombardi B
雄性F-344大鼠喂食含0.05% DL-乙醇的甲基缺乏L-氨基酸限定饲料15周。将从肝脏表面突出的结节从周围组织中分离出来，并将从结节中分离的多聚腺苷酸化RNA逆转录。通过聚合酶链反应扩增包含密码子120-290的p53基因区域，并对cDNA进行测序。在12只大鼠中的7只获得的结节中检测到突变。在所有7个病例中，都存在相同的两个点突变。第一个位于密码子246的第一个碱基，由C->T转换（C：G->T：A，Arg->Cys）组成;第二个位于密码子247的第二个碱基，由G->T颠换（G：C->T：A，Arg->Leu）组成。它的结论是，肝癌的致癌物质乙醇诱导特定的热点p53基因突变，这是在不同的网站上观察到的突变发生在大鼠单独喂养的肝癌甲基缺乏饮食。结果还首次证明了乙烯利对大鼠具有致突变性。
Male F-344 rats were fed for 15 weeks a methyl-deficient L-amino acid defined diet containing 0.05% DL-ethionine. Nodules protruding from the surface of the liver were dissected free of surrounding tissue, and polyadenylated RNA isolated from the nodules was reverse transcribed. The region of the p53 gene comprising codons 120-290 was amplified by the polymerase chain reaction, and cDNAs were sequenced. Mutations were detected in nodules obtained from 7 of 12 rats. In all seven cases, the same two point mutations were present. The first was at the first base of codon 246 and consisted of a C-->T transition (C:G-->T:A, Arg-->Cys), while the second was at the second base of codon 247 and consisted of a G-->T transversion (G:C-->T:A, Arg-->Leu). It is concluded that the hepatocarcinogen ethionine induces specific hot-spot p53 gene mutations; this is in contrast to the mutations at various sites previously observed to occur in rats fed a hepatocarcinogenic methyl-deficient diet alone. The results also provide the first evidence that ethionine is mutagenic in the rat.