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J.Health Sci., 52(2), 160-168, 2006
Suppression of Amphibian Metamorphosis by Bisphenol A and Related Chemical Substances
Yasushi Goto,a Shigeyuki Kitamura,*, b Keiko Kashiwagi,a Ken Oofusa,c Osamu Tooi,d Katsutoshi Yoshizato,e Jin Sato,a Shigeru Ohta,b and Akihiko Kashiwagia
aInstitute for Amphibian Biology, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashihiroshima 739-8526, Japan, bGraduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan, cProPhoenix Company Limited, Hiroshima Techno Plaza, 3-13-26 Kagamiyama, Higashihiroshima 739-0046, Japan, dBiotechnology Research Laboratory, Towa Kagaku Co., Ltd., 3-13-26 Kagamiyama, Higashihiroshima 739-0046, Japan, and eLaboratory of Developmental Biology, Department of Biological Science, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Hiashihiroshima 739-8526, Japan
This investigation attempts to clarify the effects of the plastic monomer bisphenol A (BPA) and related chemicals on 3,3',5-triiodothyronine (T3)-induced and spontaneous anuran tadpole tail regression. T3-induced tail regression was found to be suppressed by BPA and tetrabromobisphenol A (TBBPA), tetrachlorobisphenol A (TCBPA), and tetramethylbisphenol A (TMBPA). T3-treated Rana rugosa tadpole tails displayed marked apoptotic features, including DNA fragmentation and ladder-like profiles, as opposed to essentially little or no fragmentation and ladder formation for BPA, TBBPA, TCBPA and TMBPA-treated tails. BPA and related compounds also inhibited Silurana tropicalis spontaneous metamorphosis controlled by endogenous circulating thyroid hormone (TH). These results indicate that BPA and related compounds are TH antagonists. In transgenic Xenopus laevis tadpoles carrying plasmid DNA containing TH response element (TRE) and 5'-upstream promoter region of the TH receptor (TR) bA1 gene linked to a green fluorescent protein (EGFP) gene, T3 induced a strong EGFP expression in the hind limbs, while T3 plus BPA, TBBPA, TCBPA or TMBPA suppressed the expression, suggesting BPA and related chemicals all act in preventing the binding of T3 to TR, resulting in inhibition of TR-mediated gene expression.
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