Oxidative damage to DNA and nucleotide and its prevention

DNA和核苷酸的氧化损伤及其预防

基本信息

批准号：
12213137
负责人：
KASAI Hiroshi
金额：
$ 25.54万
依托单位：
University of Occupational and Environmental Health
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12213137/
关键词：
8-OH-dG OGG1 MTH1 Orf135 2-OH-ATP 8-Cl-dGTP 8-ヒドロキシデオキシグアノシン Fpg Orf17 6価クロム酸化損傷 5-OH-CTP 8-ヒドロキシグアニン 8-クロル-dGTP 2-OH-dATP クロロゲン酸 4NQO 3'-methyl-4-DAB

项目摘要

Following results were obtained during 5 years. 1) Ribonucleotide 2-OH-ATP was efficiently hydrolyzed by human MTH1 protein ; 2) After administration of azo dye, 3'-methyl-4-dimethylaminoazobenzen to mice and rats, 8-OH-dG in DNA and its repair activity in liver were increased. These results suggested that oxidative stress is involved in the liver carcinogenesis ; 3) 8-Chloro-dGTP, a hypochlorous acid-modified nucleotide, is hydrolyzed by hMTH1, the human MutT homolog ; 4) 8-hydroxyguanine leves in DNA, its repair activity, and hOGG1 and hMTH1 mRNA expression in human lung alveolar epithelial cells were induced by crocidolite asbestos treatment ; 5) The oxidized pyrimidine ribonucleotide, 5-hydroxy-CTP, was hydrolyzed efficiently by the Escherichia coli recombinant Orf135 protein ; 6) Acute arsenite treatment induced 8-hydroxyguanine formation in DNA and inhibition of repair activity in cultured human cells ; 7) A new automated method to analyze urinary 8-hydroxydeoxyguanosine by a high-performance liquid chromatography-electrochemical detector system was developed ; 8) In the liver of 3'-methyl-4-dimethylamino-azobenzene-treated mouse, a smaller, 32-kDa 8-oxoguanine DNA glycosylase was detected ; 9) During caspase-dependent apoptosis, a mouse OGG1 fragment was detected. A relationship between Oxidative DNA damage and apoptosis was suggested.

5年间取得了以下成果。 1) 核糖核苷酸2-OH-ATP被人MTH1蛋白高效水解； 2)给小鼠和大鼠施用偶氮染料3'-甲基-4-二甲基氨基偶氮苯后，DNA中的8-OH-dG及其在肝脏中的修复活性增加。这些结果表明氧化应激参与了肝癌的发生； 3) 8-Chloro-dGTP，一种次氯酸修饰的核苷酸，被人类 MutT 同源物 hMTH1 水解； 4)青石棉处理诱导人肺泡上皮细胞中DNA中8-羟基鸟嘌呤的水平、其修复活性以及hOGG1和hMTH1 mRNA表达； 5) 氧化型嘧啶核糖核苷酸5-羟基-CTP被大肠杆菌重组Orf135蛋白高效水解； 6) 急性亚砷酸盐处理诱导DNA中8-羟基鸟嘌呤的形成并抑制培养的人体细胞的修复活性； 7) 开发了高效液相色谱-电化学检测系统自动分析尿8-羟基脱氧鸟苷的新方法； 8) 在3'-甲基-4-二甲氨基-偶氮苯处理的小鼠肝脏中，检测到较小的32-kDa 8-氧代鸟嘌呤DNA糖基化酶； 9) 在半胱天冬酶依赖性细胞凋亡过程中，检测到小鼠 OGG1 片段。提出了氧化 DNA 损伤和细胞凋亡之间的关系。