The polybrominated diphenyl ether mixture DE-71 is mildly estrogenic

Area of Science:

• Environmental Science
• Toxicology
• Endocrinology

Background:

• Polybrominated diphenyl ethers (PBDEs) are prevalent environmental contaminants.
• PBDEs are suspected endocrine disruptors with potential estrogenic activity.

Purpose of the Study:

• To evaluate the estrogenic potential of the PBDE mixture DE-71.
• To investigate DE-71's effects on estrogen-sensitive cell lines and in vivo mouse models.

Main Methods:

• Utilized MCF-7 breast cancer cell proliferation assays.
• Employed ovariectomized mice to assess reproductive tract trophic effects.
• Administered DE-71 via subcutaneous injection or oral gavage, alone or with estradiol, for 3 or 34 days.
• Measured liver weights and cytochrome P450 enzyme activities.

Main Results:

• DE-71 stimulated MCF-7 cell proliferation, an effect blocked by antiestrogen.
• DE-71 cotreatment modulated estradiol's effects in MCF-7 cells and potentiated uterine weight increase in mice.
• In vivo, DE-71's estrogenic effects on uterine epithelial height and vaginal epithelial thickness varied by administration route, duration, and mouse strain (BALB/c vs. C57BL/6).
• DE-71 increased liver weight across different mouse models, independent of estrogen receptor-alpha.
• Oral DE-71 administration increased hepatic CYP1A and CYP2B activities, while subcutaneous administration primarily increased CYP2B.

Conclusions:

• DE-71 exhibits weak estrogenic activity.
• The estrogenicity of DE-71 in mice is dependent on the route and duration of exposure.
• BALB/c mice are more sensitive to DE-71's effects on estrogen target tissues compared to C57BL/6 mice.
• DE-71-induced liver weight increase occurs independently of estrogen receptor-alpha.