Estrogenic potential of halogenated derivatives of nonylphenol ethoxylates and carboxylates.
Halogenated derivatives of nonylphenol and of its alkylates are generated during drinking water disinfection and treatment procedures. In this paper we analyze the potential of these compounds to interact with the estrogen receptor and to activate hormone-regulated gene promoters. We used the recombinant yeast assay (RYA) and the human breast cancer cell MCF7 proliferation assay for both estrogenic and antiestrogenic activities and the enzyme-linked receptor assay to examine in vitro binding to the receptor. Many nonylphenol derivatives were very weak estrogens in our functional tests when compared to nonylphenol while retaining a substantial affinity for the estrogen receptor in vitro. Antiestrogenicity tests demonstrated that brominated nonylphenol and most of the carboxylated compounds studied here behaved as estrogenic antagonists in the RYA. We also detected an increased cytotoxicity for the carboxylated derivatives in both yeast and mammalian cells. We conclude that derivatization may mask the apparent estrogenicity of nonylphenol, but the resulting compounds still represent a potential hazard since they are still able to bind the estrogen receptor and to influence the physiological response to estrogens. Our results also illustrate the advantage of combining different methods to assay estrogenicity of unknown substances.
García-Reyero
Natàlia
N
Institut de Biologia de Barcelona, Consejo Superior de Investigaciones Científicas, Jordi Girona, 18, 08034 Barcelona, Spain.
Requena
Vanessa
V
Petrovic
Mira
M
Fischer
Birgit
B
Hansen
Peter-Diedrich
PD
Díaz
Alfredo
A
Ventura
Francesc
F
Barceló
Damià
D
Piña
Benjamin
B
D001667:Binding, Competitive; D001681:Biological Assay; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D005026:Ethylene Glycols / Q000378:metabolism; D006801:Humans; D006846:Hydrocarbons, Halogenated / Q000378:metabolism* / Q000633:toxicity; D008024:Ligands; D011960:Receptors, Estrogen / Q000378:metabolism*; D018675:Toxicity Tests; D014407:Tumor Cells, Cultured; D018508:Water Purification; D015003:Yeasts; D001616:beta-Galactosidase
D004967:Estrogens; D005026:Ethylene Glycols; D006846:Hydrocarbons, Halogenated; D008024:Ligands; D011960:Receptors, Estrogen; C021754:terics; D001616:beta-Galactosidase