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.

二恶英及其受管理法规的相关化合物由一组二恶英，二苯并呋喃和共浮PCB组成，因为它们以芳基氢化碳（AHR）依赖性方式施加毒性，通常表现为2,3,7,7,8,8-TCDD，最多的毒性毒性毒物中有毒性的毒性杂物替代了。实际上，人类会从环境中结合使用这些化合物，但可能的健康影响和这些同类物的毒性机制在很大程度上是未知的。在本研究中，我们将实验室啮齿动物暴露于TCDD和PCB中，研究了AHR依赖性和独立毒性的剂量反应关系，并进行了基因分析分析，以分子基础提供有关毒性机制的信息。我们发现的新观察结果是五倍。首先，仅剂量的TCDD非常低（50 ng/kg B.W.，P.O。）显着降低了学习绩效。其次，低剂量的PCB126（500 ng/kg b.w.，其剂量相当于50 ng teq/kg b.w.）的神经行为效应降低了学习绩效。第三，以2.0 mg/kg b.w.的剂量口服PCB153的大坝。在GD15上，学习表现有明显的干扰。第四，TCDD和PCB153的共同管理降低了显着的学习绩效。最后，在这项研究中，从相同的后代窝中提取RNA，并进行全球基因表达和分析分析，因此，叶酸受体1和前列腺素D2合酶的基因表达受到了极大的改变，以表明它们是单独暴露于TCDD或TCDD或PCB的指示器。