焦炉工尿中多环芳烃羟基代谢产物与尿8-羟基脱氧鸟苷及外周血OGG1甲基化的关系

发布时间：2018-04-16 20:33

本文选题：多环芳烃 + 8-羟基脱氧鸟苷　；参考：《山西医科大学》2017年硕士论文

【摘要】：目的:1.探究职业多环芳烃(Polycyclic aromatic hydrocarboins,PAHs)暴露和生活习惯对焦炉作业工人尿中8-羟基脱氧鸟苷(8-hydroxydeoxyguanosine,8-OHdG)的影响及剂量反应关系。2.探讨职业多环芳烃暴露及生活习惯对焦炉工外周血OGG1甲基化水平的影响。方法:选取某焦化厂焦炉工365人作为接触组,水厂和物业管理144人作为对照组,利用调查问卷进行一般情况收集,通过高效液相色谱法检测研究对象晨尿中PAHs四种羟基代谢物尿2-NAP(2-hydroxynathalene,2-NAP)、2-FLU(2-hydroxyfluorene,2-FLU)、9-PHE(9-hydroxyphenanthrene,9-PHE)、1-羟基芘(1-hydroxypyrene,1-OHP)以及氧化损伤标志物8-OHd G水平。焦磷酸测序仪测定工人外周血OGG1基因4个位点甲基化水平。采用荧光实时定量PCR检测外周血OGG1表达水平。结果:1.接触组焦化厂区环境中PAHs和苯并[a]芘(Benzoapyrene,BaP)总量的中位数高于对照组厂区(P0.01)。接触组工人尿PAHs 4种羟基代谢物高于对照组(P0.01)。2.尿1-OHP、2-NAP、及ΣOH-PAHs高暴露组工人尿8-OHdG浓度高于中暴露组和低暴露组,差别具有统计学意义(P0.05);重度吸烟组工人尿8-OHdG浓度高于轻度吸烟组和不吸烟组,差别具有统计学意义(P0.05);重度饮酒组工人尿8-OHdG浓度高于轻度饮酒组和不饮酒组,差别具有统计学意义(P0.05)。多因素Logistic回归分析显示,在调整性别、饮酒、2-FLU、2-NAP、9-PHE混杂因素后,年龄、吸烟和尿1-OHP与尿8-OHdG的浓度增高密切相关,OR分别为1.39(95%CI:1.01-1.89),1.46(95%CI:1.05-2.03),1.68(95%CI:1.16-2.44)。且经趋势检验,尿8-OHdG高浓度的发生随着年龄、吸烟指数及尿1-OHP的增长而增加(P for trend0.05)。分析吸烟与尿1-OHP对尿8-OHdG浓度影响的交互作用,结果显示尿1-OHP高暴露伴随轻度或重度吸烟习惯的工人尿中出现高浓度8-OHd G的可能性分别是尿1-OHP低暴露且不吸烟工人的4.28倍(95%CI:1.32-13.86)和5.05倍(95%CI:1.63-15.67)。3.接触组工人外周血OGG1位点1、位点2、位点3、位点4及4个位点均值甲基化水平低于对照组(P0.05)。尿2-FLU高暴露组工人外周血OGG1位点均值低于中暴露组与低暴露组(0.00 vs 1.50 vs 2.11),(1.70 vs 1.82 vs 2.35),差别具有统计学意义(P0.05);经多元线性回归分析,结果显示,吸烟与工人外周血OGG1甲基化水平存在线性回归关系,随着吸烟暴露水平的升高,外周血OGG1位点3甲基化水平降低0.3%,外周血OGG1位点均值甲基化水平降低0.6%(P0.05)。结论:1.尿1-OHP和吸烟对焦炉工人尿8-OHdG浓度影响具有交互作用,吸烟的职业多环芳烃接触人群将导致机体更严重的DNA氧化损伤。2.吸烟高暴露可致工人外周血OGG1甲基化水平降低,在焦炉工人中进行控烟,对预防机体DNA氧化损伤具有重要意义。本课题为国家自然科学基金“组蛋白泛素化关键因子RING2在苯并(a)芘致细胞周期阻滞中的作用(编号: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).
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R13

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