In vitro estrogenicity of polybrominated diphenyl ethers, hydroxylated PDBEs, and polybrominated bisphenol A compounds.
By I. Meerts, R. Letcher, S. Hoving, G. Marsh, Åke Bergman, J. Lemmen, B. Burg, A. Brouwer. Environmental Health Perspectives, 2001
758 citations recorded by the source corpus.
Polybrominated diphenyl ethers (PBDEs) are used in large quantities as additive flame retardants in plastics and textile materials. PBDEs are persistent compounds and have been detected in wildlife and in human adipose tissue and plasma samples. In this study, we investigated the (anti)estrogenic potencies of several PBDE congeners, three hydroxylated PBDEs (HO-PBDEs), and differently brominated bisphenol A compounds in three different cell line assays based on estrogen receptor (ER)-dependent luciferase reporter gene expression. In human T47D breast cancer cells stably transfected with an estrogen-responsive luciferase reporter gene construct (pEREtata-Luc), 11 PBDEs showed estrogenic potencies, with concentrations leading to 50% induction (EC(50)) varying from 2.5 to 7.3 microM. The luciferase induction of the most potent HO-PBDE [2-bromo-4-(2,4,6-tribromophenoxy)phenol] exceeded that of estradiol (E(2)), though at concentrations 50,000 times higher. As expected, brominated bisphenol A compounds with the lowest degree of bromination showed highest estrogenic potencies (EC(50) values of 0.5 microM for 3-monobromobisphenol A). In an ER alpha-specific, stably transfected human embryonic kidney cell line (293-ER alpha-Luc), the HO-PBDE 4-(2,4,6-tribromophenoxy)phenol was a highly potent estrogen with an EC(50) < 0.1 microM and a maximum 35- to 40-fold induction, which was similar to E(2). In an analogous ER beta-specific 293-ER betas-Luc cell line, the agonistic potency of the 4-(2,4,6-tribromophenoxy)phenol was much lower (maximum 50% induction compared to E(2)), but EC(50) values were comparable. These results indicate that several pure PBDE congeners, but especially HO-PBDEs and brominated bisphenol A-analogs, are agonists of both ER alpha and ER beta receptors, thus stimulating ER-mediated luciferase induction in vitro. These data also suggest that in vivo metabolism of PBDEs may produce more potent pseudoestrogens.
Subfields: Cancer Research, Health, Toxicology and Mutagenesis
View Paper: https://www.semanticscholar.org/paper/f39681d2db0335769d8504804373caab6f583bde
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Cancer Research
In Health, Toxicology and Mutagenesis
Citations in the corpus
- Review of risk from potential emerging contaminants in UK groundwater. (2012, background): “Polybrominated diphenyl ether (PBDE) flame retardants have been found to bioaccumulate and have potential endocrine disrupting properties (Hooper and McDonald, 2000; Meerts et al., 2001; Rahman et al., 2001).”
- Fireproof killer whales (Orcinus orca): flame-retardant chemicals and the conservation imperative in the charismatic icon of British Columbia, Canada (2006, background): “In addition, there is evidence for other endocrine-disrupting influences for both PBDE parent congeners and some of their metabolites, including estrogenicity (Meerts et al. 2001).”
- In vitro molecular mechanisms of bisphenol A action. (2007, background): “genic activities and are able to bind to the ER! [141].”
- Brominated flame retardants: cause for concern? (2003, positive): “Meerts et al. (2001) has demonstrated in vitro that the binding affinity of TBBPA to TTR is greater than that of T4 (up to 10 times more potent than T4).”
- Large effects from small exposures. III. Endocrine mechanisms mediating effects of bisphenol A at levels of human exposure. (2006, background): “The effects of delivery of these EDCs to target cells by serum and its binding proteins changed the relative estrogenic activities of these two compounds and predicted that BPA would be more than 500-fold more active than octylphenol in endocrine disruption of the fetal mouse (21).”