Mutagenicity of a unique 8-oxoguanine in a human Ha-ras sequence in mammalian cells.
Mutagenicity of a unique 8-oxoguanine in a human Ha-ras sequence in mammalian cells.
复制标题
哺乳动物细胞中人类 Ha-ras 序列中独特的 8-氧代鸟嘌呤的致突变性。
DOI：
10.1093/carcin/16.11.2779
复制
发表时间：
1995
期刊：
影响因子：
4.7
通讯作者：
Gentil,A
中科院分区：
文献类型：
--
作者：
LePage,F;Margot,A;Grollman,AP;Sarasin,A;Gentil,A
使用单链穿梭载体在哺乳动物细胞中研究了 DNA 中独特的 8-氧代鸟嘌呤残基的加工。将在密码子 12 的第一个 (G1) 或第二个鸟嘌呤 (G2) 上携带病变的人 Ha-ras 片段插入穿梭质粒中。染色体外 DNA 在动物细胞中复制、提取并用于转化细菌以进行扩增和个体化。细菌克隆的 DNA 测序表明 8-氧代鸟嘌呤的体内诱变能力约为 4%。 8-氧代鸟嘌呤的存在不会极大地影响后代的存活。位于G1或G2位置的8-氧代鸟嘌呤诱导的突变频率之间没有观察到显着差异。大多数针对病变水平的突变是 G 到 T 的颠换。这些碱基取代分别诱导 P21ras 蛋白中甘氨酸变为半胱氨酸 (G1) 或缬氨酸 (G2)。这些突变可能有助于原癌基因的激活，导致自发性肿瘤发生。
The processing of a unique 8-oxoguanine residue in DNA has been studied in mammalian cells using a single-stranded shuttle vector. A fragment of human Ha-rascarrying the lesion on the first (G1) or the second guanine (G2) of codon 12 was inserted in a shuttle plasmid. Extrachromosomal DNA is replicated in animal cells, extracted and used to transform bacteria to be amplified and individualized. DNA sequencing of bacterial clones showed the mutagenic potency of 8-oxoguaninein vivoto be ∼4%. The presence of the 8-oxoguanine does not greatly affect survival of the progeny. No significant difference was observed between the mutation frequencies induced by 8-oxoguanine located either at the G1 or G2 position. The majority of the mutations, targeted at the lesion level, are G to T transversions. These base substitutions induced respectively glycine to cysteine (G1) or valine (G2) change in the P21rasprotein. These mutations may contribute to activation of the protooncogene, leading to spontaneous tumorigenesis.