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Title: Estrogen receptor- and aryl hydrocarbon receptor-mediated activities of a coal-tar creosote

Abstract

A coal-tar creosote was examined for estrogen receptor (ER)- and aryl hydrocarbon receptor (AhR)-mediated activity using a battery of mechanistically based assays. In vitro, creosote was found to bind to the mouse ER, bind to the human sex hormone-binding globulin, and elicit partial agonist activity in reporter gene assays in transiently transfected MCF-7 cells. Based on competitive binding to the mouse ER, creosote contains approximately 165 mg/L of estradiol-equivalents. Creosote effectively transformed the AhR in vitro and induced a Cyplal-regulated luciferase reporter gene in transiently transfected Hepa 1c1c7 cells. Based on dose-response curves, creosote contains approximately 730 mg/L of dioxin-equivalents. Creosote did not exhibit any AhR-mediated antiestrogenic activity in vitro. In vivo, creosote significantly induced liver pentoxyresorufin O-depentylation and ethoxyresorufin-O-deethylation (EROD) in a dose-dependent manner in ovariectomized (OVX) ICR mice, but did not increase uterine weight wet or vaginal cornification, due possibly to AhR-mediated antiestrogenic activity. In OVX DBA/2 mice, a strain less responsive to AhR ligands, creosote induced liver EROD to a lesser extent, but still did not show an increase in uterine wet weight or vaginal cornification. These results demonstrate that coal-tar creosote exhibits AhR- and ER-mediated activity in vitro, but its dioxinlike activity may suppress estrogenic responsesmore » in vivo.« less

Authors:
; ; ; ; ; ;
Publication Date:
Research Org.:
Michigan State Univ., East Lansing, MI (US)
OSTI Identifier:
20067666
Alternate Identifier(s):
OSTI ID: 20067666
Resource Type:
Journal Article
Journal Name:
Environmental Toxicology and Chemistry
Additional Journal Information:
Journal Volume: 19; Journal Issue: 5; Other Information: PBD: May 2000; Journal ID: ISSN 0730-7268
Country of Publication:
United States
Language:
English
Subject:
01 COAL, LIGNITE, AND PEAT; CREOSOTE; ESTROGENS; RECEPTORS; COAL TAR; BIOASSAY; ENZYME INDUCTION; OXIDOREDUCTASES

Citation Formats

Fielden, M.R., Wu, Z.F., Sinal, C.J., Jury, H.H., Bend, J.R., Hammond, G.L., and Zacharewski, T.R. Estrogen receptor- and aryl hydrocarbon receptor-mediated activities of a coal-tar creosote. United States: N. p., 2000. Web. doi:10.1897/1551-5028(2000)019<1262:ERAAHR>2.3.CO;2.
Fielden, M.R., Wu, Z.F., Sinal, C.J., Jury, H.H., Bend, J.R., Hammond, G.L., & Zacharewski, T.R. Estrogen receptor- and aryl hydrocarbon receptor-mediated activities of a coal-tar creosote. United States. doi:10.1897/1551-5028(2000)019<1262:ERAAHR>2.3.CO;2.
Fielden, M.R., Wu, Z.F., Sinal, C.J., Jury, H.H., Bend, J.R., Hammond, G.L., and Zacharewski, T.R. Mon . "Estrogen receptor- and aryl hydrocarbon receptor-mediated activities of a coal-tar creosote". United States. doi:10.1897/1551-5028(2000)019<1262:ERAAHR>2.3.CO;2.
@article{osti_20067666,
title = {Estrogen receptor- and aryl hydrocarbon receptor-mediated activities of a coal-tar creosote},
author = {Fielden, M.R. and Wu, Z.F. and Sinal, C.J. and Jury, H.H. and Bend, J.R. and Hammond, G.L. and Zacharewski, T.R.},
abstractNote = {A coal-tar creosote was examined for estrogen receptor (ER)- and aryl hydrocarbon receptor (AhR)-mediated activity using a battery of mechanistically based assays. In vitro, creosote was found to bind to the mouse ER, bind to the human sex hormone-binding globulin, and elicit partial agonist activity in reporter gene assays in transiently transfected MCF-7 cells. Based on competitive binding to the mouse ER, creosote contains approximately 165 mg/L of estradiol-equivalents. Creosote effectively transformed the AhR in vitro and induced a Cyplal-regulated luciferase reporter gene in transiently transfected Hepa 1c1c7 cells. Based on dose-response curves, creosote contains approximately 730 mg/L of dioxin-equivalents. Creosote did not exhibit any AhR-mediated antiestrogenic activity in vitro. In vivo, creosote significantly induced liver pentoxyresorufin O-depentylation and ethoxyresorufin-O-deethylation (EROD) in a dose-dependent manner in ovariectomized (OVX) ICR mice, but did not increase uterine weight wet or vaginal cornification, due possibly to AhR-mediated antiestrogenic activity. In OVX DBA/2 mice, a strain less responsive to AhR ligands, creosote induced liver EROD to a lesser extent, but still did not show an increase in uterine wet weight or vaginal cornification. These results demonstrate that coal-tar creosote exhibits AhR- and ER-mediated activity in vitro, but its dioxinlike activity may suppress estrogenic responses in vivo.},
doi = {10.1897/1551-5028(2000)019<1262:ERAAHR>2.3.CO;2},
journal = {Environmental Toxicology and Chemistry},
issn = {0730-7268},
number = 5,
volume = 19,
place = {United States},
year = {2000},
month = {5}
}