Molecular properties of the aryl hydrocarbon (Ah) receptor /
| Main Author: | |
|---|---|
| Other Authors: | , , |
| Format: | Thesis Book |
| Language: | English |
| Published: |
1991.
|
| Subjects: | |
| Online Access: | Link to OAKTrust copy |
| Abstract: | Tritiated PCDD and PCDF congeners were synthesized and the kinetics of their association with the Wistar rat and C57BL/6 mouse hepatic cytosolic Ah receptor was determined. The affinities of these congeners for the Ah receptor as determined by conventional Scatchard plot analysis varied from 5 to 9 nM in the rat and from 1 to 9 nM in the mouse. The temperature-dependent rate of association of these ligands with the Ah receptor was studied and the competing thermal inactivation of the unbound receptor was determined. The equilibrium dissociation constants were obtained as the ratio of the rate constants for dissociation and formation, of the receptor-ligand complexes The results of the kinetic studies in the rat showed that: 1) 2,3,7,-TrCDD and 1,2,7,8-TCDF bound significantly more slowly to the Ah receptor than the other radioligands at all temperatures and this paralleled the lower biochemical and toxic potencies of the congeners; 2) the Kd values obtained kinetically were in the pM range; and 3) the ligands with the highest biochemical and toxic potencies showed the highest affinity for the Ah receptor. The MCF-7, T47-D, MDA-MB-231, and HS578 transformed human breast cancer cell lines were treated with [3H]-2,3,7,8-TCDD and the cytosolic and nuclear Ah receptor-complexes were isolated. The velocity sedimentation S values for the cytosolic and nuclear complexes were in the 9 to 10 S and 5.5 to 7 S range, respectively. Gel permeation column chromatography of the Ah receptor-complexes were also determined and the elution profiles and estimated molecular weights of the cytosolic and nuclear receptor-complexes from the human breast cancer cells were similar to those reported for rodent Ah receptor-complexes. Using [125I]-2,3,-dibromo-7-iododibenzo-p-dioxin (IDBrDD), the cytosolic Ah receptor-complex was identified in six of the 35 primary mammary tumors. The comparative properties of the cytosolic Ah receptor-complexes in primary tumors and transformed cell lines exhibit both similarities and differences. The results confirm the variability of human Ah receptor-complexes which are comparable to the interspecies differences in the properties of the Ah receptor from the rat and mouse. |
|---|---|
| Item Description: | Typescript (photocopy). Vita. "Major subject: Toxicology." |
| Physical Description: | xiii, 148 leaves : illustrations ; 29 cm |
| Bibliography: | Includes bibliographical references. |