Mechanism of action of toxic halogenated aromatics

Journal Article · Fri Feb 01 00:00:00 UTC 1985 · Environ. Health Perspect.; (United States)

DOI:https://doi.org/10.2307/3429884· OSTI ID:5384616

Vickers, A E.M.; Sloop, T C; Lucier, G W

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related halogenated aromatic hydrocarbons are a highly toxic class of environmental contaminants, as evidenced by numerous cases of accidental poisonings of human and animal populations and their extreme toxic potency in laboratory animals. The proposed model for the mechanism of action of TCDD and related compounds is analogous to that of the stereoid hormones, which modulate gene expression through a receptor mechanism. In the steroid receptor model, the compound enters the cell cytoplasm where it acts as a specific ligand, binding selectively to a high affinity receptor protein. Bound to the appropriate ligand, the receptor concentrates in the nucleus where its increased association with chromatin leads to altered gene expression. This model has been useful in characterizing the Ah receptor; however, it does not provide a unifying hypothesis for all biochemical and toxic effects associated with exposure to halogenated aromatic hydrocarbons. Several findings suggest that a primary factor in determining TCDD toxicity might be tissue and species specific factors that control the actions of Ah receptor(s) in target tissues. Furthermore, numerous mechanisms might be involved. Clarifying the mechanism(s) for TCDD toxicity would enhance our ability to predict human health consequences to toxic halogenated aromatic hydrocarbons and would provide a more rational basis for risk analysis.

• Research Organization: National Institutes of Health, Research Triangle Park, NC
• DOE Contract Number: NONE
• OSTI ID: 5384616
• Journal Information: Environ. Health Perspect.; (United States), Journal Name: Environ. Health Perspect.; (United States) Vol. 59; ISSN EVHPA
• Country of Publication: United States
• Language: English

Related Subjects

560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
560306 -- Chemicals Metabolism & Toxicology-- Man-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AROMATICS
BIOLOGICAL MODELS
BODY
CHLORINATED AROMATIC HYDROCARBONS
DIGESTIVE SYSTEM
DIOXIN
GLANDS
HALOGENATED AROMATIC HYDROCARBONS
HAZARDS
HEALTH HAZARDS
HETEROCYCLIC COMPOUNDS
LABORATORY ANIMALS
LIVER
LYMPHATIC SYSTEM
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PHARMACOLOGY
RISK ASSESSMENT
THYMUS
TOXICITY