Suppression of amphibian metamorphosis by bisphenol A and related chemical substances
Suppression of amphibian metamorphosis by bisphenol A and related chemical substances
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DOI：
10.1248/jhs.52.160
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发表时间：
2006-04-01
影响因子：
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通讯作者：
Kashiwagi, A
中科院分区：
文献类型：
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作者：
Goto, Y;Kitamura, S;Kashiwagi, A
本研究旨在阐明塑料单体双酚A(BPA)及其相关化学物质对3，3‘，5-三碘甲腺原氨酸(T-3)诱导的无尾蝌蚪尾部退缩和自发退尾的影响。BPA和四溴双酚A(TBBPA)、四氯双酚A(TCBPA)和四甲基双酚A(TMBPA)可抑制T-3诱导的尾部回归。T-3处理的Rana rugosa蝌蚪尾巴显示出显著的凋亡特征，包括DNA片段化和梯形轮廓，而BPA、TBBPA、TCBPA和TMBPA处理的尾巴基本上很少或几乎没有片段化和梯形形成。双酚A及其相关化合物还能抑制受内源性循环甲状腺激素(TH)控制的热带林蛙自发变态。这些结果表明，双酚A及其相关化合物为TH拮抗剂。在携带含有TH反应元件(TrE)和TH受体(TR)βAI基因5‘上游启动子区域并与绿色荧光蛋白(EGFP)基因相连的质粒DNA的转基因非洲爪哇蝌蚪中，T-3诱导后肢有较强的EGFP表达，而T-3加BPA、TBBPA、TCBPA或TMBPA则抑制其表达，这表明BPA和相关化学物质都在阻止T-3与TrR结合，从而抑制了Trr介导的基因表达。
This investigation attempts to clarify the effects of the plastic monomer bisphenol A (BPA) and related chemicals on 3,3',5-triiodothyronine (T-3)-induced and spontaneous anuran tadpole tail regression. T-3-induced tail regression was found to be suppressed by BPA and tetrabromobisphenol A (TBBPA), tetrachlorobisphenol A (TCBPA), and tetramethylbisphenol A (TMBPA). T-3-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) beta AI gene linked to a green fluorescent protein (EGFP) gene, T-3 induced a strong EGFP expression in the hind limbs, while T-3 plus BPA, TBBPA, TCBPA or TMBPA Suppressed the expression, suggesting BPA and related chemicals all act in preventing the binding of T-3 to TR, resulting in inhibition of TR-mediated gene expression.