Chlorinated hydrocarbons: estrogens and antiestrogens.
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.
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Texas A&M University, College Station 77843-4466, USA.
Krishnan
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D000818:Animals; D001483:Base Sequence; D004965:Estrogen Antagonists / Q000633:toxicity*; D006801:Humans; D008969:Molecular Sequence Data; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology*
D004965:Estrogen Antagonists; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon