Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa , Ottawa, Ontario K1N 6N5, Canada.
Environ Sci Technol. 2012 Mar 6;46(5):2967-75. doi: 10.1021/es2043992. Epub 2012 Feb 16.
There are large differences in sensitivity to the toxic and biochemical effects of dioxins and dioxin-like compounds (DLCs) among vertebrates. Previously, we demonstrated that the difference in sensitivity between domestic chicken (Gallus gallus domesticus) and common tern (Sterna hirundo) to aryl hydrocarbon receptor 1 (AHR1)-dependent changes in gene expression following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is based upon the identities of the amino acids at two sites within the ligand binding domain of AHR1 (chicken--highly sensitive; Ile324_Ser380 vs common tern--250-fold less sensitive than chicken; Val325_Ala381). Here, we tested the hypotheses that (i) the sensitivity of other avian species to TCDD, 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), and 2,3,7,8-tetrachlorodibenzofuran (TCDF) is also determined by the amino acids at sites that are equivalent to sites 324 and 380 in chicken, and (ii) Ile324_Ala380 and Val324_Ser380 genotypes confer intermediate sensitivity to DLCs in birds. We compared ligand-induced transactivation function of full-length AHR1s from chicken, common tern, ring-necked pheasant (Phasianus colchicus; Ile324_Ala380) and Japanese quail (Coturnix japonica; Val324_Ala380), and three Japanese quail AHR1 mutants. The results support our hypothesis that avian species can be grouped into three general classes of sensitivity to DLCs. Both AHR1 genotype and in vitro transactivation assays predict in vivo sensitivity. Contrary to the assumption that TCDD is the most potent DLC, PeCDF was more potent than TCDD at activating Japanese quail (13- to 26-fold) and common tern (23- to 30-fold) AHR1. Our results support and expand previous in vitro and in vivo work that demonstrated ligand-dependent species differences in AHR1 affinity. The findings and methods will be of use for DLC risk assessments.
脊椎动物对二恶英和类二恶英化合物 (DLCs) 的毒性和生化效应的敏感性存在很大差异。此前，我们证明了鸡（Gallus gallus domesticus）和普通燕鸥（Sterna hirundo）对芳基烃受体 1 (AHR1) 依赖性基因表达变化的敏感性差异，这种差异是基于 AHR1 配体结合域中两个位点的氨基酸身份（鸡——高度敏感；Ile324_Ser380 与普通燕鸥——比鸡敏感 250 倍；Val325_Ala381）。在这里，我们检验了以下假设：(i) 其他鸟类对 TCDD、2,3,4,7,8-五氯二苯并呋喃 (PeCDF) 和 2,3,7,8-四氯二苯并呋喃 (TCDF) 的敏感性也由鸡中相当于第 324 和 380 位的氨基酸决定，以及 (ii) Ile324_Ala380 和 Val324_Ser380 基因型赋予鸟类对 DLCs 的中间敏感性。我们比较了来自鸡、普通燕鸥、环颈雉（Phasianus colchicus；Ile324_Ala380）和日本鹌鹑（Coturnix japonica；Val324_Ala380）的全长 AHR1 以及三种日本鹌鹑 AHR1 突变体的配体诱导的反式激活功能。结果支持我们的假设，即鸟类可以分为对 DLCs 敏感性的三个一般类别。AHR1 基因型和体外反式激活测定均预测体内敏感性。与 TCDD 是最有效的 DLC 的假设相反，PeCDF 对激活日本鹌鹑（13-26 倍）和普通燕鸥（23-30 倍）AHR1 的活性比 TCDD 更强。我们的结果支持并扩展了先前的体外和体内研究，这些研究表明 AHR1 亲和力存在物种依赖性的配体依赖性差异。这些发现和方法将对 DLC 风险评估有用。
