Comparative in vitro transformation of the aromatic hydrocarbon receptor (AhR) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 3-methylcholanthrene (MC)

Conference · Wed Feb 26 04:00:00 EST 1992 · FASEB Journal (Federation of American Societies for Experimental Biology); (United States)

OSTI ID:7206292

Riddick, D S; Harper, P A; Okey, A B; Riddick, D S ^[1]

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1. Univ. of Toronto, Ontario (Canada)

The induction of CYP1A1 by halogenated (e.g. TCDD) and nonhalogenated (e.g. MC) aromatic hydrocarbons is mediated by the AhR. In cytosol prepared from the mouse hepatoma cell line Hepa-1, AhR bound TCDD with 3 to 4-fold greater affinity than MC, whereas TCDD was 960-fold more potent than MC as an inducer of aryl hydrocarbon hydroxylase (AHH) activity in cultured Hepa-1 cells. The objective of this study was to compare the potency and efficacy of TCDD and MC with respect to transformation of the cytosolic AhR to its DNA-binding form. Following incubation of Hepa-1 cytosol with TCDD or MC at 30 C for 4 h, the extent of AhR transformation was assessed by measuring interaction of the AhR-ligand complex with a {sup 32}P-labeled 26-bp oligonucleotide containing a single dioxin-responsive element (DRE) consensus sequence in a gel retardation assay. Concentration-response studies indicated that TCDD and MC did not differ significantly in AhR transformation potency, but MC displayed only about 70% of the efficacy of TCDD. In vitro transformation efficacy appears to be a determinant of AHH induction efficacy, but the small difference between TCDD and MC in transformation potency does not seem adequate to explain quantitatively the large difference in AHH induction potency displayed by these ligands.

• OSTI ID: 7206292
• Report Number(s): CONF-9204141--
• Conference Information: Journal Name: FASEB Journal (Federation of American Societies for Experimental Biology); (United States) Journal Volume: 6:4
• Country of Publication: United States
• Language: English

Related Subjects

3-METHYLCHOLANTHRENE
560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
AROMATICS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
COMPARATIVE EVALUATIONS
CONDENSED AROMATICS
DAYS LIVING RADIOISOTOPES
DIOXIN
DISEASES
DOSE-RESPONSE RELATIONSHIPS
EVALUATION
HEPATOMAS
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
IN VITRO
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGANDS
LIGHT NUCLEI
MAMMALS
MEMBRANE PROTEINS
METABOLISM
MICE
NEOPLASMS
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
POLYCYCLIC AROMATIC HYDROCARBONS
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
RODENTS
TRACER TECHNIQUES
TUMOR CELLS
VERTEBRATES