發(fā)布時(shí)間：2018-03-27 13:24

  本文選題：鎘離子　切入點(diǎn)：毒性　出處：《內(nèi)蒙古農(nóng)業(yè)大學(xué)》2017年碩士論文

【摘要】：鎘金屬污染對(duì)人類健康的影響一直備受關(guān)注。當(dāng)機(jī)體攝入鎘后會(huì)對(duì)組織和器官造成不同程度的急性和慢性損傷。大量文獻(xiàn)還報(bào)道了鎘毒性與癌癥的發(fā)生有關(guān)。但是,關(guān)于鎘的致癌機(jī)理卻一直未有定論。一般認(rèn)為,鎘通過(guò)破壞機(jī)體內(nèi)氧化還原平衡態(tài)間接損傷包括DNA在內(nèi)的細(xì)胞成分。此外,有實(shí)驗(yàn)表明體內(nèi)氧化還原態(tài)失衡會(huì)進(jìn)一步破壞DNA修復(fù)系統(tǒng),造成體內(nèi)DNA損傷的富集,增加基因突變。然而,關(guān)于鎘對(duì)DNA結(jié)構(gòu)的直接損傷卻鮮有報(bào)道。本文運(yùn)用分子動(dòng)力學(xué)和量子化學(xué)計(jì)算方法,研究了鎘離子和DNA雙鏈結(jié)構(gòu)的直接相互作用。我們發(fā)現(xiàn)鎘離子可以特異性地結(jié)合到DNA大溝中的胸腺嘧啶堿基上,破壞原有A-T堿基配對(duì)并形成一個(gè)新的錯(cuò)配結(jié)構(gòu)。通過(guò)量化計(jì)算得知該結(jié)合狀態(tài)是室溫穩(wěn)定的、不可逆的。這一錯(cuò)配結(jié)構(gòu)可導(dǎo)致單核苷酸多態(tài)性(SNP)從而引起DNA變性。從而提出了一種新的鎘離子直接破壞DNA結(jié)構(gòu)的結(jié)合狀態(tài)。這種結(jié)合不會(huì)造成DNA雙鏈的斷裂,因此不容易被實(shí)驗(yàn)檢測(cè)到。這一發(fā)現(xiàn)對(duì)實(shí)驗(yàn)中位點(diǎn)的發(fā)現(xiàn)提供了指導(dǎo),同時(shí)也有利于人們進(jìn)一步理解鎘的基因毒性。
[Abstract]:The effects of cadmium contamination on human health have been a matter of concern. When the body ingested cadmium, it causes varying degrees of acute and chronic damage to tissues and organs. A large number of literatures have also reported that cadmium toxicity is related to the occurrence of cancer. It is generally believed that cadmium indirectly damages the cellular components, including DNA, by destroying the redox equilibrium in the body. Some experiments have shown that the redox imbalance in vivo will further destroy the DNA repair system, lead to the enrichment of DNA damage in vivo and increase gene mutation. The direct damage of cadmium to DNA structure is seldom reported. In this paper, molecular dynamics and quantum chemistry methods are used. The direct interaction between cadmium ion and DNA double strand structure has been studied. We found that cadmium ion can bind specifically to the thymidine base in the large groove of DNA. The original A-T base pairs are destroyed and a new mismatch structure is formed. The quantitative calculation shows that the binding state is stable at room temperature. Irreversible. This mismatch structure can lead to the denaturation of DNA by single nucleotide polymorphism (SNPs). Therefore, a new cadmium ion directly destroys the binding state of DNA structure. This kind of binding does not result in the break of DNA double strand. Therefore, it is not easy to be detected by experiments. This discovery provides guidance for the discovery of sites in the experiment, and also helps people to further understand the genetic toxicity of cadmium.
【學(xué)位授予單位】：內(nèi)蒙古農(nóng)業(yè)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R114

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 古力;;謹(jǐn)防“鎘污染”事件再發(fā)生[J];現(xiàn)代職業(yè)安全;2009年11期

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本文編號(hào)：1671693