Superfund Research Program

Halogenated Aromatics

Project Leader: Stephen H. Safe
Grant Number: P42ES004917
Funding Period: 1995 - 2000

Project-Specific Links

Final Progress Reports

Year:   1999 

Research during the past year has primarily focused on the endocrine-active chemicals and their responses in several bioassays. One study has focused on the activities on the pesticide methoxychlor and its metabolites. Researchers compared the activity of 2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), an estrogenic metabolite of methoxychlor, at estrogen receptor (ER ) and estrogen receptor (ER ). Human hepatoma cells (HepG2) were transiently transfected with either human or rat ER or ER plus an estrogen-responsive, complement 3-luciferase construct containing a complement 3 gene promoter sequence linked to a luciferase reporter gene. After transfection, cells were treated with various concentrations of HPTE in the presence (for detecting antagonism) or absence (for detecting agonism) of 17 -estradiol. HPTE was an ER agonist in HepG2 cells, with EC₅₀ values of approximately 5 x 10^-8 and 10^-8 M for human and rat ER , respectively. In contrast, HPTE had minimal agonist activity with either human or rat ER and almost completely abolished 17 -estradiol-induced ER -mediated activity. Moreover, HPTE behaved as an ER agonist and an ER antagonist with other estrogen-responsive promoters (ERE-MMTV and vtERE) in HepG2 and HeLa cells. This study demonstrated the complexity involved in determining the mechanism of action of endocrine-active chemicals that may act as agonists or antagonists through one or more hormone receptors.