Relationship between health effects and gene polymorphisms among people exposed to low level dioxins

我们计划在以下三个主题上进行研究。第一;二、二恶英暴露对基因表达影响的个体差异;二、氧化应激水平评价方法的建立;三、二恶英暴露与多环芳烃的交互作用.受试者是MSWIs和IWI的工人。采集血液样本，测量二恶英同系物的水平，并分析二恶英相关基因CYP 1A 1、CYP 1B 1和AhR以及氧化应激相关基因hOGG 1的表达水平。将各基因表达水平除以各二恶英同系物暴露水平，得到相应二恶英同系物暴露水平的基因表达强度指数（IGED）。IGED的分布呈单峰或双峰型。采用聚类分析将所有受试者分为2个亚组，即高诱导组（I）和低诱导组（II）。在一般人群水平上，血液二恶英水平与CYP 1A 1和CYP 1B 1之间存在相关性 ...更多信息 表达水平，且I组的相关性突出。从基因表达的角度来看，组I具有高敏感性，组II具有低敏感性二恶英暴露。我们可以从单个群体中分离出高敏感性群体，这对于进一步研究致病基因的多态性是很有价值的.尿中8-羟基脱氧鸟苷（8-OHdG）是一种氧化损伤的核苷，可能是DNA或核苷酸库的修复产物，是反映人体暴露于有害因素后氧化应激水平的有用指标。在使用该指数评估二恶英暴露引起的氧化应激之前，需要考虑导致方差的主要因素。本文首先研究了几种采样方法，并比较了它们的稳定性。结果表明，第二次晨尿与第一次晨尿相比，8-OHdG值稳定，尿量排泄率更稳定。然后研究了8-OHdG在不同温度下储存时的稳定性。在室温（25℃）下放置24小时无任何差异。此外，氧化应激水平随睡眠时间的变化而变化，其变化不是线性的，而是非线性的U型曲线.对可能接触二恶英和多环芳烃的城市生活垃圾焚烧厂和工业垃圾焚烧厂工人进行了健康影响调查。在轮班前采集血液和尿液样本，在轮班结束时采集尿液样本。血液二恶英，多环芳烃的尿液代谢产物，和氧化应激标记8-OH-dG在尿液中的同类物进行了测量。经多元回归分析，控制不同工厂和吸烟的影响，血液中二恶英水平与氧化应激水平无关。至于多环芳烃，萘的暴露水平，而不是芘的氧化应激有关。少

We planed our research on the following three themes. First; individual differences on the responses of gene expression to the dioxin exposure, second ; development of the methods to evaluate oxidative stress level, third; the interaction effect between the exposure to dioxins and to PAHs.1. Subjects were workers at MSWIs and an IWI. Blood samples were taken and the levels of dioxin congeners were measured and the expression levels of dioxin related genes CYP1A1, CYP1B1, and AhR and of an oxidative stress related gene hOGG1 were analyzed. Each gene expression level was divided by each dioxin congener level to get the index of gene expression strength per dioxin congener exposure level (IGED). Distributions of IGEDs showed simple peak or dual peaks. Whole subjects were split to 2 sub-groups using cluster analysis, those were high induction group (I) and low induction group (II). At the level of general population there were associations between blood dioxin levels and CYP1A1 and CYP1B1 … More expressions levels, and the relations were prominent in group I. From the view point of gene expressions, group I has high sensitivity and group II has low sensitivity to dioxin exposure. We could split high sensitivity group from single population which is quite valuable to make further study to clarify the responsible gene polymorphisms.2. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), which is an oxidatively damaged nucleoside and may be a repair product of DNA or nucleotide pool, is a useful index for oxidative stress level of human exposed to noxious factors. Before using this index to estimate oxidative stress induced by exposure to dioxin, it is needed to consider the major factors inducing the variances. We first studied several sampling methods and compared their stableness. The results showed that the second morning void will show stable 8-OHdG value compared to the first morning void, and excretion rate by urine volume was still more stable. We then studied the stableness of 8-OHdG in urine when stored in different temperatures. Leave at room temperature, which was 25℃, for 24 hours did not make any difference. Further more, oxidative stress level changed by sleeping time and the change was not linear but non-linear U shaped pattern.3. We surveyed on health effect of workers at MSWI and industrial waste incinerator, who have possible risk of exposure to dioxin and PAH. Blood and urine samples were taken before the work shift and urine samples were taken at the end of the work shift. Congeners of blood dioxin, urinal metabolites of PAHs, and an oxidative stress marker 8-OH-dG in urine were measured. By multiple regression analysis controlling the effects of different factory and smoking, blood dioxin level did not relate to oxidative stress level. Concerning the PAHs, exposure level of naphthalene but not of pyrene was related to oxidative stress. Less