Department of Biology, Woods Hole Oceanographic Institution, Woods Hole, MA 02543, USA.
Aquat Toxicol. 2010 Nov 1;100(3):238-45. doi: 10.1016/j.aquatox.2010.07.021. Epub 2010 Jul 23.
Persistent organic pollutants such as halogenated aromatic hydrocarbons (HAHs) biomagnify in food webs and accumulate to high concentrations in top predators like odontocete cetaceans (toothed whales). The most toxic HAHs are the 2,3,7,8-substituted halogenated dibenzo-p-dioxins and furans, and non-ortho-substituted polychlorinated biphenyls (PCBs), which exert their effects via the aryl hydrocarbon receptor (AHR). Understanding the impact of HAHs in wildlife is limited by the lack of taxon-specific information about the relative potencies of toxicologically important congeners. To assess whether Toxic Equivalency Factors (TEFs) determined in rodents are predictive of HAH relative potencies in a cetacean, we used beluga and mouse AHRs expressed in vitro from cloned cDNAs to measure the relative AHR-binding affinities of ten HAHs from five different structural classes. The rank order of mean IC(50)s for competitive binding to beluga AHR was: TCDD<TCDF<PCB-126<PCB-169<PCB-77<PCB-81⋘PCB-156∼PCB-128<PCB-105<PCB-118. The rank order of mean IC(50)s for binding to the mouse AHR was TCDD<TCDF<PCB-126<PCB-169<PCB-81<PCB-77<PCB-156≪PCB-128∼PCB-105∼PCB-118. K(i) values for binding of HAHs to beluga and mouse AHRs were highly correlated (r(2)=0.96). Comparison of K(i) values suggested that the beluga AHR had a higher affinity than the mouse AHR for most of the HAHs tested, consistent with the ∼2-fold higher [(3)H]TCDD binding affinity determined previously. These results are consistent with the World Health Organization mammalian TEFs for non- and mono-ortho PCB congeners. The comparatively high HAH binding affinities of the beluga AHR relative to those of an AHR from a dioxin-responsive mouse suggests that beluga, and perhaps cetaceans in general, may be particularly sensitive to the toxic effects of AHR agonists. Further study is warranted in order to more fully address this important question affecting protected and endangered species.
持久性有机污染物，如卤代芳烃（HAHs），在食物网中生物放大，并在齿鲸等顶级捕食者中积累到高浓度。最有毒的 HAHs 是 2,3,7,8-取代的卤代二苯并-p-二恶英和呋喃，以及非邻位取代的多氯联苯（PCBs），它们通过芳烃受体（AHR）发挥作用。由于缺乏关于毒理学上重要同系物相对效力的特定分类群信息，因此对野生动物中 HAHs 的影响的了解受到限制。为了评估在啮齿动物中确定的毒性等效因子（TEFs）是否可预测鲸类动物中 HAHs 的相对效力，我们使用体外从克隆 cDNA 表达的白鲸和小鼠 AHR 来测量来自五个不同结构类别的十种 HAHs 的相对 AHR 结合亲和力。对竞争结合白鲸 AHR 的平均 IC50 的排序顺序为：TCDD<TCDF<PCB-126<PCB-169<PCB-77<PCB-81<PCB-156∼PCB-128<PCB-105<PCB-118。对结合小鼠 AHR 的平均 IC50 的排序顺序为：TCDD<TCDF<PCB-126<PCB-169<PCB-81<PCB-77<PCB-156≪PCB-128∼PCB-105∼PCB-118。HAHs 与白鲸和小鼠 AHR 结合的 K(i) 值高度相关（r(2)=0.96）。比较 K(i) 值表明，与测试的大多数 HAHs 相比，白鲸 AHR 对 HAHs 的亲和力更高，这与先前确定的约 2 倍更高的[(3)H]TCDD 结合亲和力一致。这些结果与世界卫生组织非和单-邻位 PCB 同系物的哺乳动物 TEFs 一致。与来自对二恶英有反应的小鼠的 AHR 相比，白鲸 AHR 对 HAHs 的相对较高的结合亲和力表明，白鲸，也许一般来说，鲸类可能对 AHR 激动剂的毒性作用特别敏感。为了更充分地解决这个影响受保护和濒危物种的重要问题，进一步的研究是必要的。
