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

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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