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The profiling of gene expression evoked by co-exposure to dioxin and polychlorinated biphenyl.

共同暴露于二恶英和多氯联苯引起的基因表达谱。

基本信息

批准号：
15201014
负责人：
TOHYAMA Chiharu
金额：
$ 18.55万
依托单位：
The University of Tokyo (2005-2006)National Institute for Environmental Studies (2003-2004)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2006
项目状态：
已结题

项目摘要

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.

受行政监管的二恶英及其相关化合物是由二恶英、二苯并呋喃和共面多氯联苯组成的一组化合物，因为它们以依赖芳烃(AhR)的方式发挥毒性，典型的表现为2，3，7，8-TCDD，这是这组化合物中毒性最大的同系物。事实上，人类是从环境中接触到这些化合物的组合，但这些同系物的组合可能对健康造成的影响和毒性机制在很大程度上是未知的。在本研究中，我们将TCDD和多氯联苯联合暴露于实验室啮齿动物，研究了AHR依赖和独立毒性的剂量-反应关系，并进行了基因图谱分析，从分子基础上提供了毒性机制的信息。我们发现的新观察结果有五个方面。首先，单独服用非常低剂量的TCDD(50 ng/kg B.W.，P.O.)显著降低了学习成绩。第二，小剂量PCB126(500 ng/kg体重，相当于50 ng TEQ/kg体重)对神经行为的影响。降低了学习成绩。第三，灌胃给予PCB153 2.0 mg/kg体重剂量的水坝。GD15有明显的学习成绩障碍。第四，TCDD和PCB153联合使用会显著降低学习成绩。最后，在本研究中，从同一窝后代中提取RNA，并进行全局基因表达和图谱分析，结果叶酸受体1和前列腺素D2合成酶的基因表达发生了显著变化，表明它们分别是单独接触TCDD或TCDD+多氯联苯的指标。