镉与大沟中胸腺嘧啶结合引起的DNA变性

发布时间：2018-03-27 13:24

本文选题：镉离子　切入点：毒性　出处：《内蒙古农业大学》2017年硕士论文

【摘要】：镉金属污染对人类健康的影响一直备受关注。当机体摄入镉后会对组织和器官造成不同程度的急性和慢性损伤。大量文献还报道了镉毒性与癌症的发生有关。但是,关于镉的致癌机理却一直未有定论。一般认为,镉通过破坏机体内氧化还原平衡态间接损伤包括DNA在内的细胞成分。此外,有实验表明体内氧化还原态失衡会进一步破坏DNA修复系统,造成体内DNA损伤的富集,增加基因突变。然而,关于镉对DNA结构的直接损伤却鲜有报道。本文运用分子动力学和量子化学计算方法,研究了镉离子和DNA双链结构的直接相互作用。我们发现镉离子可以特异性地结合到DNA大沟中的胸腺嘧啶碱基上,破坏原有A-T碱基配对并形成一个新的错配结构。通过量化计算得知该结合状态是室温稳定的、不可逆的。这一错配结构可导致单核苷酸多态性(SNP)从而引起DNA变性。从而提出了一种新的镉离子直接破坏DNA结构的结合状态。这种结合不会造成DNA双链的断裂,因此不容易被实验检测到。这一发现对实验中位点的发现提供了指导,同时也有利于人们进一步理解镉的基因毒性。
[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.
【学位授予单位】：内蒙古农业大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R114

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