| Co-Investigator(Kenkyū-buntansha) |
YONEMOTO Junzo National Institute for Environmental Studies, Research Center for Environmental Risk, Dupty Director, 環境リスク研究センター, 副センター長 (30072664)
AOKI Yasunobu National Institute for Environmental Studies, Research Center for Environmental Risk, Leader, 環境リスク研究センター, 室長 (20159297)
OHSAKO Seiichiro The University of Tokyo, Graduate School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (00274837)
NISHIMURA Noriko National Institute for Environmental Studies, Research Center for Environmental Risk, Senior Researcher, 環境リスク研究センター, 主任研究員 (10097800)
KAKEYAMA Masaki The University of Tokyo, Graduate School of Medicine, Assistant Professor, 大学院医学系研究科, 助手 (30353535)
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| Research Abstract |
Dioxin and its related compounds that are under administrative regulation are comprised of a group of compounds of dioxins, dibenzofurans and coplanar PCBs because they exert toxicities in an arylhydrocarbon (AhR)-dependent manner, as typically shown by 2,3,7,8-TCDD, the most toxic congener among this group compounds. In reality, humans are exposed to these compounds in combination from the environment, but possible health effects and the mechanism of toxicities exposed combinations of these congeners are largely unknown. In the present study, we exposed laboratory rodents to TCDD and PCB in combination, studied dose-response relationship of AhR-dependent and independent toxicities and carried out gene profiling analysis to provide information on the toxicity mechanism on a molecular basis. The new observations we found are five-fold. First, a very low dose of TCDD alone (50 ng/kg b.w., p.o.) significantly decreased learning performance. Second, neurobehavioral effects of a low dose of PCB126 (500 ng/kg b.w., the dose of which is equivalent to 50 ng TEQ/kg b.w.) decreased the learning performance. Third, dams that were administered PCB153 orally at a dose of 2.0 mg/kg b.w. on GD15 had marked disturbance in learning performance. Fourth, co-administration of TCDD and PCB153 decreased significant learning performance. Lastly, in this study, RNA was extracted from the same litter of offspring, and subjected to global gene expression and profiling analyses, and as a result, gene expression of folate receptor 1 and prostaglandin D2 synthase were remarkably altered to suggest that they are indicators for exposure to TCDD alone or TCDD plus PCB, respectively.
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