Chlorinated hydrocarbons: estrogens and antiestrogens.

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related compounds bind to the intracellular aryl hydrocarbon (Ah) receptor and induce a diverse spectrum of biochemical and toxic responses. Ah receptor agonists also modulate several endocrine pathways, and research in several laboratories has shown that TCDD and related compounds inhibit estrogen (E2)-induced responses in the rodent mammary and uterus and in human breast cancer cell lines. The mechanisms of interaction between the TCDD- and E2-induced signaling pathways are complex and some of the inhibitory effects may be related to 5'-flanking inhibitory-dioxin responsive elements (i-DREs) in target genes. The antiestrogenic and antitumorigenic activity of Ah receptor agonists has been used to prepare a series of relatively non-toxic alkyl polychlorinated dibenzofurans which have clinical potential for treatment of mammary cancer.

• Authors: S Safe, V Krishnan
• Journal: Toxicology letters (Toxicol Lett) Vol. 82-83 Pg. 731-6 (Dec 1995) ISSN: 0378-4274 [Print] Netherlands
• PMID: 8597135 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S., Review)

Chemical References

• Estrogen Antagonists
• Polychlorinated Dibenzodioxins
• Receptors, Aryl Hydrocarbon

Topics

• Animals
• Base Sequence
• Estrogen Antagonists (toxicity)
• Humans
• Molecular Sequence Data
• Polychlorinated Dibenzodioxins (toxicity)
• Receptors, Aryl Hydrocarbon (physiology)