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

受行政监管的二恶英及其相关化合物由一组二恶英、二苯并呋喃和共面多氯联苯化合物组成，因为它们以芳烃（AhR）依赖的方式发挥毒性，如典型的2,3,7,8- tcdd所示，它是这类化合物中毒性最大的同系物。实际上，人类从环境中以组合形式接触到这些化合物，但接触这些同系物组合可能产生的健康影响和毒性机制在很大程度上是未知的。本研究将TCDD和PCB联合暴露于实验室啮齿动物，研究ahr依赖性和独立毒性的剂量-反应关系，并进行基因谱分析，从分子基础上提供毒性机制信息。我们发现的新观察结果是五倍的。首先，极低剂量的TCDD （50 ng/kg b.w., p.o.）会显著降低学习成绩。其次，低剂量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表现。第三，在GD15时口服剂量为2.0 mg/kg b.w.的PCB153对幼鼠的学习表现有明显的干扰。第四，TCDD和PCB153联合使用显著降低学习成绩。最后，在本研究中，从同一窝子代中提取RNA，并进行全局基因表达和谱分析，结果表明叶酸受体1和前列腺素D2合成酶的基因表达显著改变，表明它们分别是TCDD单独暴露或TCDD加PCB暴露的指标。

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.