Studies on the role of the Ah receptor in hexachloro-benzene-induced porphyria
Many of the effects of hexachlorobenzene (HCB) resemble those of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), whose effects are initiated by its binding to the AH receptor, the regulatory gene product of the Ah locus. I investigated the ability of HCB to interact with the AH receptor and the involvement of this protein in HCB-induced porphyria. The induction of two cytochrome P450 isozymes regulated by the Ah locus was also examined in light of their possible role in the pathogenesis of HCB- and TCDD-induced porphyria. HCB competitively inhibited the in vitro specific binding of ({sup 3}H)-TCDD to the rat hepatic Ah receptor (K{sub I} = 2.1 {mu}M) without affecting the solubility of ({sup 3}H)TCDD. Following the administration of HCB to rats, the number of ({sup 3}H)TCDD specific binding sites was reduced by up to 40%. HCB induced cytochromes P450b, P450e, P450c, and P450d, confirming that it is a mixed-type P450 inducer. The presence of porphyria in mice was assessed by measuring urinary and hepatic porphyrins and hepatic uroporphyrinogen decarboxylase activity.
- Research Organization:
- Rochester Univ., NY (USA)
- OSTI ID:
- 7164257
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
CHLORINATED AROMATIC HYDROCARBONS
TOXICITY
DIOXIN
METABOLIC DISEASES
PATHOGENESIS
RECEPTORS
BIOLOGICAL FUNCTIONS
BIOCHEMICAL REACTION KINETICS
DECARBOXYLASES
ENZYME INDUCTION
LIVER
MICE
MIXED-FUNCTION OXIDASES
PORPHYRINS
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ANIMALS
AROMATICS
BODY
CARBON-CARBON LYASES
CARBOXY-LYASES
CARBOXYLIC ACIDS
DIGESTIVE SYSTEM
DISEASES
ENZYMES
FUNCTIONS
GENE REGULATION
GLANDS
HALOGENATED AROMATIC HYDROCARBONS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
LYASES
MAMMALS
MEMBRANE PROTEINS
ORGANIC ACIDS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
OXIDOREDUCTASES
OXYGENASES
PROTEINS
REACTION KINETICS
RODENTS
VERTEBRATES
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