【作者】 苏世标；

【导师】 童建；

【作者基本信息】 苏州大学 ， 卫生毒理学， 2006， 硕士

【摘要】 目的:从氧化损伤和基因甲基化的角度,研究氡暴露对靶细胞的早期生物学效应。寻找氡暴露人群的易感性标记物,从而为氡危害的早期预防提供基础资料。方法:(1)以染氡大鼠和中国核工业总公司721矿的91名铀矿工(其中50名井下铀矿工,24名地表铀矿工,17名行政办公工作人员)作为研究对象。将雄性Wistar大鼠随机分为对照组、低、中和高4个剂量组,每组5只。暴露组大鼠整体暴露于HD-3型多功能生态氡室,保持剂量率相对恒定。各组大鼠均于末次暴露后2~3h内采样检测。分析10年该铀矿的氡及其子体监测资料,找出最佳监测时段,在该时段内采用固体核径迹法对铀矿工氡累积暴露水平进行估测,再按与染氡大鼠累积暴露剂量相近的剂量分组。(2)测定各组职业人群与大鼠超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量,观察比较低、中和高剂量组和对照组SOD活性和MDA含量的差异。(3)用甲基化特异性PCR(MSP)检测大鼠气管-支气管上皮细胞中p16基因甲基化,探讨其与氡子体累积暴露剂量的相互关系;同时研究铀矿工痰细胞中p16基因和6-氧-甲基嘌呤-DNA甲基转移酶(MGMT)的甲基化,观察比较基因甲基化率的变化趋势与氡子体累积暴露剂量的关系。(4)利用片段性长度多态性聚合酶链反应(PCR-RFLP)检测谷胱甘肽-S-转移酶P1(GSTP1)基因多态,比较基因型分布与p16和MGMT基因甲基化的关系。结果:(1)5月和9月的氡浓度水平接近年平均浓度,平均平衡因子F=0.36。(2)职业流行病学调查结果表明,各组的一般特征如性别、民族、年龄、工龄、工时、居住史、家族遗传史在各组人群中的分布无统计学差异,表明各组均衡可比。(3)在对照组、低、中和高剂量职业氡暴露人群外周血中,SOD活性分别为(116.5±12.3)U/ml、(89.6±8.3)U/ml、(63.6±8.9) U/ml和40.9±7.6U/ml,MDA含量分别为(1.1±0.4)nmol/ml、(2.1±0.3)nmol/ml、(3.3±0.5)nmol/ml和(5.3±0.9)nmol/ml,各组间差别有统计学意义(P<0.05)。随着氡子体累积暴露剂量的增加,SOD活性逐渐降低, MDA含量逐渐升高。在对照组、低、中和高剂量吸入染氡大鼠外周血中, SOD活性分别为(1393.40±88.30)U/ml、(1198.60±132.44)U/ml、(1198.60±132.44)U/ml和(1098.60±50.90)U/ml,MDA含量分别为(0.53±0.13)nmol/ml、(1.89±0.13)nmol/ml、(2.38±0.12) nmol/ml和(2.88更多还原

【Abstract】 Objective: To study biological effect of radon on target cells of rats and uranium miner and seek for the early biomakers of oxidative stress damage and DNA methylation.Methods: (1) Twenty male Wistar rats were randomly divided into four groups, one control group and three experimental groups exposed to radon. Ninety one male uranium miners from a Chinese uranium mine in Jiangxi province were also divided into four groups according to the cumulative exposure dose similar with the rats (>120WLM, 60~120WLM, 30~60WLM , 2~30WLM ). (2)The monitoring data of radon and its daughters from 1995 to 2004 were used to calculate annual and months average radon concentration. Level of radon was monitored by the method of solid nuclear traces.(3) Activity of SOD and content of MDA in peripheral blood were observed to compare differences among the groups. (4) The methylations of p16 and MGMT gene were determined by MSP,and associated with radon cumulative dose. (5) Association of GSTP1genotype with methylation of MGMT and p16 gene in sputum of uranium miners was studied.Results: (1) Radon concentration in May and September could be representative of the annual average concentration with an equilibrium factor of 0.36. (2)The confounding factors such as age, length of service, work hours per day, cigarette smoking and alcohol consumption, habitation history, and family history of lung cancer were no statistic difference in four groups.(3)The activity of SOD in human peripheral blood of each group was (116.5±12.3)U/ml, (89.6±8.3)U/ml, (63.6±8.9) U/ml and (40.9±7.6)U/ml, and the result in rats of each group was (1393.40±88.30)U/ml, (1198.60±132.44)U/ml, (1198.60±132.44)U/ml and (1098.60±50.90)U/ml, respectively. The content of MDA in human peripheral blood in each group was (1.1±0.4)nmol/ml, (2.1±0.3)nmol/ml, (3.3±0.5)nmol/ml and (5.3±0.9)nmol/ml, and the result in rats of each更多还原