本文選題：多環(huán)芳烴 + 8-羥基脫氧鳥苷�。� 參考：《山西醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:1.探究職業(yè)多環(huán)芳烴(Polycyclic aromatic hydrocarboins,PAHs)暴露和生活習(xí)慣對(duì)焦?fàn)t作業(yè)工人尿中8-羥基脫氧鳥苷(8-hydroxydeoxyguanosine,8-OHdG)的影響及劑量反應(yīng)關(guān)系。2.探討職業(yè)多環(huán)芳烴暴露及生活習(xí)慣對(duì)焦?fàn)t工外周血OGG1甲基化水平的影響。方法:選取某焦化廠焦?fàn)t工365人作為接觸組,水廠和物業(yè)管理144人作為對(duì)照組,利用調(diào)查問卷進(jìn)行一般情況收集,通過高效液相色譜法檢測(cè)研究對(duì)象晨尿中PAHs四種羥基代謝物尿2-NAP(2-hydroxynathalene,2-NAP)、2-FLU(2-hydroxyfluorene,2-FLU)、9-PHE(9-hydroxyphenanthrene,9-PHE)、1-羥基芘(1-hydroxypyrene,1-OHP)以及氧化損傷標(biāo)志物8-OHd G水平。焦磷酸測(cè)序儀測(cè)定工人外周血OGG1基因4個(gè)位點(diǎn)甲基化水平。采用熒光實(shí)時(shí)定量PCR檢測(cè)外周血OGG1表達(dá)水平。結(jié)果:1.接觸組焦化廠區(qū)環(huán)境中PAHs和苯并[a]芘(Benzoapyrene,BaP)總量的中位數(shù)高于對(duì)照組廠區(qū)(P0.01)。接觸組工人尿PAHs 4種羥基代謝物高于對(duì)照組(P0.01)。2.尿1-OHP、2-NAP、及ΣOH-PAHs高暴露組工人尿8-OHdG濃度高于中暴露組和低暴露組,差別具有統(tǒng)計(jì)學(xué)意義(P0.05);重度吸煙組工人尿8-OHdG濃度高于輕度吸煙組和不吸煙組,差別具有統(tǒng)計(jì)學(xué)意義(P0.05);重度飲酒組工人尿8-OHdG濃度高于輕度飲酒組和不飲酒組,差別具有統(tǒng)計(jì)學(xué)意義(P0.05)。多因素Logistic回歸分析顯示,在調(diào)整性別、飲酒、2-FLU、2-NAP、9-PHE混雜因素后,年齡、吸煙和尿1-OHP與尿8-OHdG的濃度增高密切相關(guān),OR分別為1.39(95%CI:1.01-1.89),1.46(95%CI:1.05-2.03),1.68(95%CI:1.16-2.44)。且經(jīng)趨勢(shì)檢驗(yàn),尿8-OHdG高濃度的發(fā)生隨著年齡、吸煙指數(shù)及尿1-OHP的增長(zhǎng)而增加(P for trend0.05)。分析吸煙與尿1-OHP對(duì)尿8-OHdG濃度影響的交互作用,結(jié)果顯示尿1-OHP高暴露伴隨輕度或重度吸煙習(xí)慣的工人尿中出現(xiàn)高濃度8-OHd G的可能性分別是尿1-OHP低暴露且不吸煙工人的4.28倍(95%CI:1.32-13.86)和5.05倍(95%CI:1.63-15.67)。3.接觸組工人外周血OGG1位點(diǎn)1、位點(diǎn)2、位點(diǎn)3、位點(diǎn)4及4個(gè)位點(diǎn)均值甲基化水平低于對(duì)照組(P0.05)。尿2-FLU高暴露組工人外周血OGG1位點(diǎn)均值低于中暴露組與低暴露組(0.00 vs 1.50 vs 2.11),(1.70 vs 1.82 vs 2.35),差別具有統(tǒng)計(jì)學(xué)意義(P0.05);經(jīng)多元線性回歸分析,結(jié)果顯示,吸煙與工人外周血OGG1甲基化水平存在線性回歸關(guān)系,隨著吸煙暴露水平的升高,外周血OGG1位點(diǎn)3甲基化水平降低0.3%,外周血OGG1位點(diǎn)均值甲基化水平降低0.6%(P0.05)。結(jié)論:1.尿1-OHP和吸煙對(duì)焦?fàn)t工人尿8-OHdG濃度影響具有交互作用,吸煙的職業(yè)多環(huán)芳烴接觸人群將導(dǎo)致機(jī)體更嚴(yán)重的DNA氧化損傷。2.吸煙高暴露可致工人外周血OGG1甲基化水平降低,在焦?fàn)t工人中進(jìn)行控?zé)?對(duì)預(yù)防機(jī)體DNA氧化損傷具有重要意義。本課題為國(guó)家自然科學(xué)基金“組蛋白泛素化關(guān)鍵因子RING2在苯并(a)芘致細(xì)胞周期阻滯中的作用(編號(hào):81273041)”。
[Abstract]:Purpose 1.To investigate the effects of occupational polycyclic aromatic hydrocarboins (PAHs) exposure and living habits on 8-hydroxydeoxyguanosine 8-hydroxydeoxyguanosine 8-OHdG in the urine of workers exposed to coke oven.To investigate the effects of occupational polycyclic aromatic hydrocarbons (PAHs) exposure and life habits on OGG1 methylation in peripheral blood of coke oven workers.Methods: 365 coke oven workers in a coking plant were selected as contact group and 144 in water plant and property management as control group.Four hydroxyl metabolites of PAHs, 2-NAPN 2-hydroxynathathaleneI, 2-FLUU 2-hydroxyfluorenene-2-fluorophane 9-hydroxyphenanthrene9-hydroxyphenanthrene9-pHEne1-hydroxypyrene1-OHP1, and the oxidative damage marker 8-OHd G, were determined by high performance liquid chromatography (HPLC).The methylation level of 4 loci of OGG1 gene in peripheral blood of workers was determined by pyrosequencing apparatus.Fluorescence real-time quantitative PCR was used to detect the expression of OGG1 in peripheral blood.The result is 1: 1.The median of total PAHs and benzo [a] pyrene Benzoapyrene Bap in the exposed group was higher than that in the control group.The urinary PAHs 4 hydroxyl metabolites in the exposed workers were higher than those in the control group (P 0.01). 2.The urinary 8-OHdG concentration in urinary 1-OHPnAP2-NAPand 危 OH-PAHs high exposure group was higher than that in moderate exposure group and low exposure group, the difference was statistically significant (P 0.05), and the urinary 8-OHdG concentration in heavy smoking group was higher than that in mild smoking group and non-smoking group.The concentration of urinary 8-OHdG in heavy drinking group was higher than that in mild drinking group and non-drinking group, and the difference was statistically significant (P 0.05).The incidence of high concentration of 8-OHdG in urine increased with the increase of age, smoking index and urinary 1-OHP.To analyze the interaction between smoking and urinary 1-OHP on urinary 8-OHdG concentration.The results showed that the incidence of high concentration of 8-OHd G in urine of workers with mild or severe smoking habit was 4.28 times than that of workers with low exposure to urinary 1-OHP and non-smoking workers (95 CI: 1.32-13.86) and 5.05 times of 95% CI: 1.63-15.670.3.The results showed that the incidence of high concentration of 8-OHd G in urine of workers with mild or severe smoking habit was 4.28 times than that of non-smoking workers.The mean methylation levels of OGG1 loci 1, 2, 3, 4 and 4 in the exposed group were lower than those in the control group (P 0.05).The mean value of OGG1 locus in peripheral blood of high exposure group of urinary 2-FLU was lower than that of moderate exposure group and low exposure group (P 0.05).There was a linear regression relationship between smoking and the level of OGG1 methylation in peripheral blood of workers. With the increase of exposure level of smoking, the level of methylation of OGG1 locus 3 in peripheral blood decreased by 0.3%, and the mean methylation level of OGG1 locus in peripheral blood decreased by 0.6% (P 0.05).Conclusion 1.Urinary 1-OHP and smoking have interaction effect on urinary 8-OHdG concentration of coke oven workers. Occupational polycyclic aromatic hydrocarbons (PAHs) exposed to smoking will lead to more serious oxidative damage of DNA. 2.High exposure to smoking can reduce the level of OGG1 methylation in peripheral blood of workers. Smoking control in coke oven workers is of great significance in preventing DNA oxidative damage.This paper is about the role of RING2, a key factor of histone ubiquitin, in cell cycle arrest induced by benzo (a) pyrene (No.: 81273041).
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R13

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本文編號(hào)：1760473