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

受到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，因为它们以芳基烃（AhR）依赖性方式发挥毒性，典型的表现是2,3,7,8-TCDD，该组化合物中毒性最强的同系物。事实上，人类会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产生的影响和毒性机制在很大程度上尚不清楚。在本研究中，我们将实验室啮齿动物暴露于TCDD和PCB的组合中，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，以提供分子基础上毒性机制的信息。我们发现的新观察结果有五重。首先，单独使用极低剂量的 TCDD（50 ng/kg b.w.，口服）会显着降低学习成绩。其次，低剂量 PCB126（500 ng/kg b.w.，其剂量相当于 50 ng TEQ/kg b.w.）的神经行为影响降低了学习表现。第三，以 2.0 mg/kg b.w. 的剂量口服 PCB153 的母鼠。 GD15 的学习表现有明显障碍。第四，TCDD 和 PCB153 的共同给药显着降低了学习成绩。最后，在本研究中，从同一窝后代中提取 RNA，并进行整体基因表达和谱分析，结果，叶酸受体 1 和前列腺素 D2 合酶的基因表达发生显着改变，表明它们分别是单独暴露于 TCDD 或 TCDD 加 PCB 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.