title: Disruption of thyroid hormone-mediated Xenopus laevis tadpole tail tip regression by hexabromocyclododecane (HBCD) and 2,2',3,3',4,4',5,5',6-nona brominated diphenyl ether (BDE206).
abstract: Thyroid hormone regulates amphibian metamorphosis, including the transformation of a tadpole into a froglet and regression of the tail. Xenopus laevis tadpole tail tips in organ culture (ex vivo) undergo regression when exposed to 3,3',5-triiodo-l-thyronine (T(3)) and interference by chemicals with this process was utilized as a bioassay to detect thyroid hormone disruption. In the present study the bioassay was further validated by investigating its response to compound induced T(3)-antagonism and - potentiation. Tadpole tail tips were exposed to two brominated flame retardants (BFRs) in presence or absence of T(3) at its EC(50) (20 nM). T(3)-induced tail tip regression was antagonized by 2,2',3,3',4,4',5,5',6-nona brominated diphenyl ether (BDE206) and potentiated by hexabromocyclododecane (HBCD) in a concentration dependent manner, which was consistent with results obtained with a in vitro T(3)-dependent proliferation bioassay termed the T-screen. Neither compound induced any effect in the absence of T(3). The results indicate that studying possible hormone disrupting effects of agonistic, antagonistic or potentiating compounds should include combined exposure with the natural hormone at around its EC(50) concentration. The results obtained with the tail tip exposures were in accordance with the T-screen predictions, and occurred at BFR-concentrations that were only 5-50 times those of T(3). The bioassay proved to be suitable not only for detecting T(3)-agonism, but also for antagonism and potentiation.
authors.affiliation: Wageningen University, Toxicology Section, 6703 HE, Wageningen, The Netherlands. merijn.schriks@wur.nl
authors.forename: Merijn
authors.initials: M
authors.lastname: Schriks
authors.forename: Elton
authors.initials: E
authors.lastname: Zvinavashe
authors.forename: J David
authors.initials: JD
authors.lastname: Furlow
authors.forename: Albertinka J
authors.initials: AJ
authors.lastname: Murk
mesh_terms: D000818:Animals; D055768:Halogenated Diphenyl Ethers; D006842:Hydrocarbons, Brominated / Q000009:adverse effects*; D066298:In Vitro Techniques; D007814:Larva; D010647:Phenyl Ethers / Q000009:adverse effects*; D013623:Tail / Q000187:drug effects*; D013963:Thyroid Hormones / Q000378:metabolism* / Q000494:pharmacology; D014284:Triiodothyronine / Q000378:metabolism / Q000494:pharmacology; D014982:Xenopus laevis / Q000502:physiology*
chemical_list: D055768:Halogenated Diphenyl Ethers; D006842:Hydrocarbons, Brominated; D010647:Phenyl Ethers; D013963:Thyroid Hormones; D014284:Triiodothyronine; C512044:2,2',3,3',4,4',5,5',6-nonabromodiphenyl ether; C089796:hexabromocyclododecane