Structure-dependent Ah receptor agonist activities of chlorinated biphenylenes

Toxicol In Vitro. 2006 Oct;20(7):1234-7. doi: 10.1016/j.tiv.2006.04.003. Epub 2006 May 3.

Abstract

Polychlorinated biphenylenes (PCBP) have been identified as combustion by-products that bind the aryl hydrocarbon receptor (AhR) and exhibit 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-like activity. This study investigates the Ah-responsiveness of 2,3,6,7-tetrachlorobiphenylene (2,3,6,7-CBP), 2,3,6-CBP, 2,3-CBP and 2-CBP in breast cancer cells. MCF-7 or ZR-75 cells were treated with different concentrations (1-100 nM) of the compounds alone to determine their activity as inducers of CYP1A1 protein expression or luciferase activity in cells transfected with a construct (pDRE(3)) containing three tandem dioxin responsive elements (DREs) linked to a luciferase reporter gene. In both assays, the order of potency was 2,3,6,7-CBP>2,3,6-CBP>2,3-CBP approximately 2-CBP, and 2,3,6,7-CBP and TCDD were equipotent. Similar results were also observed in an antiestrogenic assay in MCF-7 cells, confirming the high AhR agonist activity of 2,3,6,7-CBP in breast cancer cells.

Publication types

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

MeSH terms

  • Blotting, Western
  • Cell Line, Tumor
  • Cytochrome P-450 CYP1A1 / metabolism
  • Dose-Response Relationship, Drug
  • Estradiol / pharmacology
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism
  • Gene Expression / drug effects
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • Polychlorinated Biphenyls / chemistry
  • Polychlorinated Biphenyls / pharmacology*
  • Polychlorinated Dibenzodioxins / analogs & derivatives
  • Polychlorinated Dibenzodioxins / pharmacology
  • Receptors, Aryl Hydrocarbon / agonists*
  • Structure-Activity Relationship
  • Time Factors
  • Transfection

Substances

  • 2,3,6,7-tetrachlorobiphenylene
  • 2,3,6-trichlorobiphenylene
  • 2,3-dichlorobiphenylene
  • Estrogen Receptor alpha
  • Polychlorinated Dibenzodioxins
  • Receptors, Aryl Hydrocarbon
  • Estradiol
  • Polychlorinated Biphenyls
  • Luciferases
  • Cytochrome P-450 CYP1A1