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

A coal-tar creosote was examined for estrogen receptor (ER)- and aryl hydro carbon 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 activit y 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 vi tro and induced a Cyp1a1-regulated luciferase reporter gene in transiently transfected Hepa 1c1c7 cells. Based on dose-response curves, creosote conta ins approximately 730 mg/L of dioxin-equivalents. Creosote did not exhibit any AhR-mediated antiestrogenic activity in vitro. In vivo, creosote signif icantly induced liver pentoxyresorufin O-depentylation and ethoxyresorufin- O-deethylation (EROD) in a dose-dependent manner in ovariectomized (OVX) IC R mice, but did not increase uterine weight wet or vaginal cornification, d ue possibly to AhR-mediated antiestrogenic activity. In OVX DBA/2 mice, a s train less responsive to AhR ligands, creosote induced liver EROD to a less er extent, but still did not show an increase in uterine wet weight or vagi nal cornification. These results demonstrate that coal-tar creosote exhibit s AhR- and ER-mediated activity in vitro, bur its dioxinlike activity may s uppress estrogenic responses in vivo.