Effects of structure on binding to the 2,3,7,8-TCDD receptor protein and AHH induction-halogenated biphenyls
The quantitative structure-activity relationships (QSARs) for polychlorinated biphenyl (PCB) congeners have been determined by comparing the EC/sub 50/ values for three in vitro test systems, namely, aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) induction in rat hepatoma H-4-II-E cells and competitive binding avidities to the rat cytosolic receptor protein (using 2,3,7,8-tetrachlorodibenzo-p-dioxin as a radioligand). For several PBC congeners that are in vivo inducers of rat hepatic microsomal AHH, there was a linear correlation between the -log EC/sub 50/ values for receptor and the -log EC/sub 50/ values for AHH (or EROD) induction; moreover, a comparable linear relationship was observed between the -log EC/sub 50/ values for AHH and EROD induction. Previous in vivo studies have shown that the most active PCB congeners 3,3',4,4'-tetra-, 3,4,4',5-tetra, 3,3',4,4',5-penta-, and 3,3',4,4',5,5'-hexachlorobiphenyl, cause many of the biologic and toxic effects reported for the highly toxic halogenated aryl hydrocarbon, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Moreover, the monoortho-substituted homologs of the four coplanar PCBs also elicit comparable in vivo biologic and toxic responses. It was evident from the QSARs for PCBs that there was an excellent correspondence between the in vivo and in vitro potencies of the individual PCB congeners. 81 references, 11 figures, 4 tables.
- Research Organization:
- Texas A and M Univ., College Station
- OSTI ID:
- 5885720
- Journal Information:
- Environ. Health Perspect.; (United States), Journal Name: Environ. Health Perspect.; (United States) Vol. 61; ISSN EVHPA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
AROMATICS
CATALYSIS
CELL CONSTITUENTS
CHEMICAL ACTIVATION
CHEMICAL BONDS
CHEMICAL REACTIONS
CHLORINATED AROMATIC HYDROCARBONS
CYTOCHROME OXIDASE
DIOXIN
DISEASES
ENZYME ACTIVITY
ENZYMES
HAEM DEHYDROGENASES
HALOGENATED AROMATIC HYDROCARBONS
HEPATOMAS
HETEROCYCLIC COMPOUNDS
HYDROXYLASES
IN VITRO
IN VIVO
LIGANDS
LIVER CELLS
MAMMALS
MATHEMATICS
MEMBRANE PROTEINS
MICROSOMES
NEOPLASMS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANOIDS
OXIDATION
OXIDOREDUCTASES
PHYSICAL PROPERTIES
PROTEINS
RATS
RECEPTORS
REGRESSION ANALYSIS
RODENTS
SOMATIC CELLS
STATISTICS
STRUCTURE-ACTIVITY RELATIONSHIPS
TOXICITY
VERTEBRATES