Cikryt P, Josephy P D
Institute of Toxicology and Pharmacology, University of Würzburg, F.R.G.
Chem Biol Interact. 1989;72(1-2):57-64. doi: 10.1016/0009-2797(89)90017-3.
The binding of benzidine, 3,3'-dichlorobenzidine (3,3'-Cl2BZ), and the asymmetrically-substituted chlorinated benzidines 3,5-dichlorobenzidine (3,5-Cl2BZ) and 3,5,3'-trichlorobenzidine (Cl3BZ) to the rat hepatic cytosolic aromatic hydrocarbon (Ah) receptor was measured, in order to assess the mechanism of P-450I induction by 3,3'-Cl2BZ. Cl3BZ is the most mutagenic benzidine derivative in the Ames assay. Binding affinity to the Ah receptor protein was determined by displacement of labelled 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) from the receptor, measured with the sucrose density gradient centrifugation technique. The rank order of affinities and the apparent inhibitor constants were: Cl3BZ (4 microM) greater than 3,5-Cl2BZ (8.4 microM) greater than 3,3'-Cl2BZ (10 microM). Benzidine did not displace TCDD from the receptor protein. 4-Aminobiphenyl a structural link between the benzidine and biphenyl series competed weakly with TCDD. The 50% inhibition concentration was about 150 microM. The results are consistent with the hypothesis that the induction of P-450 enzymes by 3,3'-Cl2BZ in vivo is mediated by the Ah receptor.
为评估3,3'-二氯联苯胺（3,3'-Cl2BZ）诱导P-450I的机制，测定了联苯胺、3,3'-二氯联苯胺（3,3'-Cl2BZ）以及不对称取代的氯化联苯胺3,5-二氯联苯胺（3,5-Cl2BZ）和3,5,3'-三氯联苯胺（Cl3BZ）与大鼠肝脏胞质芳烃（Ah）受体的结合情况。Cl3BZ是艾姆斯试验中最具致突变性的联苯胺衍生物。通过蔗糖密度梯度离心技术，测定标记的2,3,7,8-四氯二苯并对二恶英（TCDD）从受体上的置换情况，从而确定与Ah受体蛋白的结合亲和力。亲和力的排序和表观抑制常数为：Cl3BZ（4 microM）＞3,5-Cl2BZ（8.4 microM）＞3,3'-Cl2BZ（10 microM）。联苯胺不能从受体蛋白上置换TCDD。4-氨基联苯是联苯胺和联苯系列之间的结构联系物，它与TCDD的竞争较弱。50%抑制浓度约为150 microM。这些结果与以下假设一致，即3,3'-Cl2BZ在体内诱导P-450酶是由Ah受体介导的。
