本文關鍵詞：DNA氧化損傷修復基因HOGG1低表達細胞株的建立及其應用研究　出處：《四川大學》2005年博士論文　論文類型：學位論文

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【摘要】：DNA損傷與修復一直是毒理學和腫瘤學研究的熱點,在眾多DNA損傷中,以自由基(free radical)引起的DNA氧化損傷(oxidative DNA damage)研究最多,被認為是啟動和促進腫瘤發(fā)生最為重要的因素。大量研究表明:活性氧(reactive oxygen species,ROS)自由基可以直接攻擊生物大分子DNA,誘發(fā)DNA鏈斷裂和多種形式的堿基修飾。在各種DNA氧化損傷中,以鳥嘌呤8位碳原子的氧化最常見,其氧化產(chǎn)物8-羥基-脫氧鳥嘌呤(7,8-dihydro-8-oxoguanine,8-OHdG)在體內(nèi)形成后較為穩(wěn)定、易于檢測,被公認為DNA氧化損傷的生物標志物(biomarker)。此外,8-OHdG最特征、最具生物學意義的危害是:DNA鏈中的鳥嘌呤G被氧化成8-OHdG后可導致DNA鏈空間構(gòu)象的改變,在DNA合成時8-OHdG優(yōu)先或等效率地與腺嘌呤A配對,從而導致DNA鏈G:C→T:A顛換,該顛換在腫瘤形成中發(fā)生最早,常見于癌基因ras和抑癌基因p53中,故此突變被認為與腫瘤的發(fā)生發(fā)展、機體細胞的老化和某些退行性疾病的發(fā)生都具有密切的關系。 人體細胞中,特異性切除和修復8-OHdG的酶是8-羥基鳥嘌呤DNA糖苷酶(human 8-oxoguanine DNA glycosylase,簡稱HOGG1),具有切除DNA雙鏈中與堿基C配對的8-OHdG的作用,從而恢復基因組中正常的G∶C配對,在維持基因組穩(wěn)定和腫瘤預防上具有舉足輕重的作用,編碼該蛋白的基因hOGG1于1997年成功克隆。 人群流行病學研究顯示:hOGG1基因在不同人群存在遺傳多態(tài)性,并與癌癥易感性密切相關,其突變或缺失將增加個體罹患腫瘤的風險。
[Abstract]:DNA damage and repair has been a hotspot in toxicology and oncology, in numerous DNA injury by free radicals (free, radical) DNA caused oxidative damage (oxidative DNA damage) of the most, is thought to initiate and promote tumorigenesis of the most important factors. A large number of studies have demonstrated that reactive oxygen species (reactive oxygen, species ROS), free radicals can attack the biological macromolecules DNA induced DNA strand breaks and base modification in various forms. In a variety of oxidative DNA damage, the most common of the 8 carbon atom of guanine oxidation, the oxidation products of 8- hydroxy desoxyguanosine (7,8-dihydro-8-oxoguanine, 8-OHdG) in the body after the formation of relatively stable, easy to detect that is recognized as a biomarker of oxidative DNA damage (biomarker). In addition, the characteristics of 8-OHdG, the most harmful biological significance is: DNA in the chain of guanine G by oxygen into 8-OHdG can lead to DNA chain Between the conformational change in the synthesis of DNA 8-OHdG and other priority or efficiently paired with adenine A, resulting in DNA chain G:C to T:A transversion, the transversion in tumor formation in the earliest, common in cancer gene Ras and tumor suppressor gene p53, this mutation is considered with the occurrence and development of tumor, are there is a close relationship between occurrence of cellular aging and certain degenerative diseases.
In human cells, specific excision and repair of 8-OHdG enzyme is 8- oxoguanine DNA glycosylase (human 8-oxoguanine DNA glycosylase, referred to as HOGG1), with DNA double chain excision and base pairing of C 8-OHdG, thus restoring G: normal genome C pairing, plays an important role in maintaining genomic stability and the prevention of cancer, hOGG1 gene encoding the protein was successfully cloned in 1997.
Epidemiological studies show that hOGG1 gene is polymorphic in different populations, and is closely related to cancer susceptibility. Mutation or deletion will increase the risk of cancer.

【學位授予單位】：四川大學
【學位級別】：博士
【學位授予年份】：2005
【分類號】：R346

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本文編號：1390479