Shinmura K, Kohno T, Kasai H, Koda K, Sugimura H, Yokota J
Biology Division, National Cancer Center Research Institute, Tokyo.
Jpn J Cancer Res. 1998 Aug;89(8):825-8. doi: 10.1111/j.1349-7006.1998.tb00635.x.
DNA glycosylase, encoded by the hOGG1 gene, repairs 8-hydroxyguanine (oh8Gua), which is an oxidatively damaged mutagenic base. To clarify whether the DNA repair activity of hOGG1 protein is involved in gastric carcinogenesis, we examined 9 gastric cancer cell lines and 35 primary gastric cancers for mutations and genetic polymorphisms of the hOGG1 gene by polymerase chain reaction-single strand conformation polymorphism analysis. A G-to-A transition was detected in a gastric cancer cell line, MKN1. This nucleotide change caused the conversion of the amino acid from Arg to His at codon 154, which is located in a domain highly conserved among human, mouse, and yeast OGG1 proteins. No mutation was detected in primary gastric cancers. We compared the distribution of the polymorphic alleles associated with enzymatic activity (hOGG1-Ser326 vs. hOGG1-Cys326) between 35 gastric cancer patients and 42 healthy individuals. Although the frequency of the Cys326 allele, associated with low enzymatic activity, in gastric cancer patients was a little higher than that in healthy individuals, the difference did not reach statistical significance. These results suggest that low hOGG1 activity due to mutations and genetic polymorphisms is involved in the development of only a small subset of gastric cancers.
由hOGG1基因编码的DNA糖基化酶可修复8-羟基鸟嘌呤（oh8Gua），它是一种氧化损伤的诱变碱基。为了阐明hOGG1蛋白的DNA修复活性是否参与胃癌发生，我们通过聚合酶链反应-单链构象多态性分析检测了9种胃癌细胞系和35例原发性胃癌中hOGG1基因的突变和基因多态性。在胃癌细胞系MKN1中检测到一个G到A的转换。这种核苷酸变化导致位于人、小鼠和酵母OGG1蛋白高度保守结构域的第154密码子处的氨基酸从精氨酸转换为组氨酸。在原发性胃癌中未检测到突变。我们比较了35例胃癌患者和42例健康个体中与酶活性相关的多态性等位基因（hOGG1-Ser326与hOGG1-Cys326）的分布。虽然与低酶活性相关的Cys326等位基因在胃癌患者中的频率略高于健康个体，但差异未达到统计学意义。这些结果表明，由于突变和基因多态性导致的hOGG1活性降低仅参与一小部分胃癌的发生。
