Molecular mechanisms of 2,3,7,8-tetrachlorodibenzo-p-dioxin cardiovascular embryotoxicity

Drug Metab Rev. 2006;38(1-2):261-89. doi: 10.1080/03602530600570099.

Abstract

2,3,7,8 Tetrachlorodibenzo-p-dioxin (TCDD) and related planar halogenated aromatic hydrocarbons are widespread environmental contaminants and potent developmental toxicants. Hallmarks of embryonic exposure include edema, hemorrhage, and mortality. Recent studies in zebrafish and chicken have revealed direct impairment of cardiac muscle growth that may underlie these overt symptoms. TCDD toxicity is mediated by the aryl hydrocarbon receptor, but downstream targets remain unclear. Oxidative stress and growth factor modulation have been implicated in TCDD cardiovascular toxicity. Gene expression profiling is elucidating additional pathways by which TCDD might act. We review our understanding of the mechanism of TCDD embryotoxicity at morphological and molecular levels.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Cardiovascular Abnormalities / chemically induced*
  • Cardiovascular Abnormalities / pathology
  • Embryo, Mammalian / physiology
  • Humans
  • Polychlorinated Dibenzodioxins / chemistry
  • Polychlorinated Dibenzodioxins / toxicity*
  • Reactive Oxygen Species / metabolism
  • Receptors, Aryl Hydrocarbon / drug effects
  • Structure-Activity Relationship
  • Teratogens / chemistry
  • Teratogens / toxicity*
  • Toxicogenetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Polychlorinated Dibenzodioxins
  • Reactive Oxygen Species
  • Receptors, Aryl Hydrocarbon
  • Teratogens
  • Vascular Endothelial Growth Factor A