【摘要】：有機(jī)物種類繁多,應(yīng)用廣泛,因此常被用于人類生活資料中作為各種主、副材料,例如在衣食住行方面分別各有以下應(yīng)用：衣物染料、食品添加劑、車輛燃料、日用品著色劑、增塑劑等等,而有機(jī)物被用作生活資料的同時也會在另一方面成為污染物,并引起相關(guān)影響人類生活的問題,例如：機(jī)動車尾氣污染、食品安全問題、氣候異常等等�？梢哉f在生活環(huán)境中處處都會接觸到各類有機(jī)物,對人類健康產(chǎn)生威脅。目前,各類環(huán)境中有機(jī)污染物與腫瘤相關(guān)疾病的關(guān)系被各領(lǐng)域廣泛關(guān)注。癌癥是基因引起的疾病,與人類相關(guān)的腫瘤相關(guān)DNA來源于原癌基因和抑癌基因。原癌基因參與促進(jìn)細(xì)胞成長、進(jìn)行有絲分裂,是致癌基因的前體,而抑癌基因則負(fù)責(zé)抑制細(xì)胞生長或是調(diào)控細(xì)胞分裂。當(dāng)調(diào)控細(xì)胞生長的基因發(fā)生損壞或突變時,細(xì)胞失去控制,進(jìn)行持續(xù)生長發(fā)展成為腫瘤。 本文選取了三類有機(jī)污染物：多環(huán)芳烴衍生物類(簡稱PAHs,包括1-羥基芘、1-氨基芘、1-芘丁醇、1-芘丁胺)；多氯聯(lián)苯類(簡稱PCBs,包括三氯聯(lián)苯、四氯聯(lián)苯、五氯聯(lián)苯、六氯聯(lián)苯)；內(nèi)分泌干擾物(三氯生(TCS)、雙酚A(BPA)),分別與兩種腫瘤相關(guān)基因啟動子區(qū)DNA(抑癌基因p53和原癌基因C-myc),運(yùn)用多種譜學(xué)方法和聚丙烯酰胺凝膠電泳手段在分子水平上研究其相互作用機(jī)制,并探求不同結(jié)構(gòu)(官能團(tuán)種類、官能團(tuán)長度、官能團(tuán)位置及分子平面性)對不同序列DNA的作用影響。主要結(jié)論為：(1)PAHs的短鏈取代基可增加共軛π鍵的離域化程度,使其易與DNA堿基對之間發(fā)生偶極作用,而長鏈取代基可使分子極性增加,利于嵌插復(fù)合物的穩(wěn)定性；-OH取代PAHs主要以溝槽和嵌插模式與DNA作用,-NH2取代PAHs主要以靜電和嵌插模式與DNA作用；而對于同類取代基的PAHs與DNA的結(jié)合能力,短鏈取代強(qiáng)于長鏈取代；PAHs與p53DNA親合力比C-myc DNA更強(qiáng)。(2)PCBs主要通過嵌插作用和靜電作用與2種DNA結(jié)合,PCBs本身的類平面性提供了嵌插作用的可能性,且C1原子使PCBs具有正的靜電勢從而與DNA存在靜電作用,雙重作用使PCBs對DNA結(jié)構(gòu)產(chǎn)生影響。(3)TCS部分嵌插入雙螺旋DNA的溝區(qū),且對p53相關(guān)DNA表現(xiàn)出更強(qiáng)的結(jié)合能力,且引起DNA雙螺旋結(jié)構(gòu)發(fā)生改變；雙酚A與人類腫瘤相關(guān)DNA的作用為嵌插和靜電作用,其結(jié)合能夠影響雙螺旋結(jié)構(gòu)并使得雙螺旋DNA含量減少。
[Abstract]:Organic compounds are widely used in many kinds of living materials, such as clothing, food, food and transportation. They are used as clothing dyes, food additives, vehicle fuels, daily necessities coloring agents. Plasticizers and so on, while organic matter is used as a means of living, it will also become a pollutant on the other hand, and cause related problems affecting human life, such as motor vehicle exhaust pollution, food safety problems, climate anomalies, etc. It can be said that in the living environment everywhere will be exposed to all kinds of organic matter, which is a threat to human health. At present, the relationship between various kinds of environmental organic pollutants and tumor-related diseases has been widely concerned. Cancer is a disease caused by genes. Human tumor-related DNA is derived from proto-oncogenes and tumor suppressor genes. Proto-oncogenes are involved in promoting cell growth and mitosis, and are precursors of oncogenes, while tumor suppressor genes are responsible for inhibiting cell growth or regulating cell division. When the gene that regulates cell growth is damaged or mutated, the cell loses control and continues to grow into a tumor. In this paper, three kinds of organic pollutants were selected: polycyclic aromatic derivatives (PAHs,) including 1-hydroxy pyrene, 1-aminopyrene, 1-pyrene butanol, 1-pyrene butylamine; Polychlorinated biphenyls (PCBs, for short including trichlorinated biphenyls, tetrachlorinated biphenyls, pentachlorinated biphenyls, hexachlorobenzenes); Endocrine disruptors (trichlorogenic (TCS), bisphenol A (BPA), and two kinds of tumor-associated gene promoter region DNA (suppressor gene p53 and proto-oncogene C-myc), respectively. Various spectroscopic methods and polyacrylamide gel electrophoresis were used to study the interaction mechanism at the molecular level, and to find out the different structures (functional groups, length of functional groups). The effect of functional group location and molecular planarity on the action of different sequences of DNA. The main conclusions are as follows: (1) the short chain substituents of PAHs can increase the degree of delocalization of conjugated 蟺 bonds and make it easy to interact with the DNA base pairs, while the long chain substituents can increase the molecular polarity and facilitate the stability of the intercalated complexes; -OH replaces PAHs mainly by groove and intercalation mode with DNA,-NH2 replaces PAHs by electrostatic and intercalation mode with DNA, and for PAHs and DNA of the same substituent, short chain is stronger than long chain. The affinity of PAHs to p53DNA is stronger than that of C-myc DNA. (2) PCBs binds to two kinds of DNA mainly through intercalation and electrostatic interaction. PCBs itself provides the possibility of intercalation. Moreover, C1 atom makes PCBs have positive electrostatic potential and has electrostatic interaction with DNA, and double action makes PCBs influence the structure of DNA. (3) TCS partially inserts the furrow region of double helix DNA, and shows stronger binding ability to p53 related DNA. The double helix structure of DNA was changed. The interaction between bisphenol A and human tumor-related DNA is intercalation and electrostatic interaction, which can affect the double helix structure and decrease the content of double helix DNA.
【學(xué)位授予單位】：南京師范大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R114

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