TY - JOUR
T1 - Structure-dependent Ah receptor agonist activities of chlorinated biphenylenes
AU - Khan, Shaheen
AU - Konstantinov, Alex
AU - Chittim, Brock
AU - McAlees, Alan
AU - Yeo, Brian
AU - Safe, Stephen
N1 - Funding Information:
The financial assistance of the National Institutes of Health (ES04176 and ES09106) and the Texas Agricultural Experiment Station is gratefully acknowledged.
PY - 2006/10
Y1 - 2006/10
N2 - 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 (pDRE3) 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 ∼ 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.
AB - 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 (pDRE3) 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 ∼ 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.
KW - Ah receptor
KW - MCF-7
KW - Polychlorinated biphenylenes
KW - ZR-75
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U2 - 10.1016/j.tiv.2006.04.003
DO - 10.1016/j.tiv.2006.04.003
M3 - Article
C2 - 16759834
AN - SCOPUS:33745997736
SN - 0887-2333
VL - 20
SP - 1234
EP - 1237
JO - Toxicology in Vitro
JF - Toxicology in Vitro
IS - 7
ER -