The promoter of the human sodium/iodide symporter responds to certain phthalate plasticisers
The promoter of the human sodium/iodide symporter responds to certain phthalate plasticisers
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DOI：
10.1016/j.mce.2005.06.009
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发表时间：
2005-12-01
影响因子：
4.1
通讯作者：
Loos, U
中科院分区：
文献类型：
--
作者：
Breous, E;Wenzel, A;Loos, U
苯-1,2-二甲酸（邻苯二甲酸）二酯（邻苯二甲酸酯）用于使塑料具有柔韧性，占塑料重量的 40%。人类接触邻苯二甲酸盐可能是通过摄入、吸入和皮肤途径，以及通过含有邻苯二甲酸盐的医疗器械的肠胃外接触。由于早期的形态学研究表明某些邻苯二甲酸盐会引起甲状腺功能亢进，因此我们认为研究六种主要邻苯二甲酸盐对钠/碘同向转运蛋白（NIS）转录活性的可能影响非常重要。邻苯二甲酸二异癸酯 (DIDP)、邻苯二甲酸丁苄酯 (BBP) 和邻苯二甲酸二辛酯 (DOP) 分别将人 NIS 启动子构建体的活性提高了 2.5 倍、2.6 倍和 2.4 倍。同样，这些邻苯二甲酸盐也增强了大鼠 NIS 内源 mRNA 的表达。 2倍。邻苯二甲酸二(2-乙基己基)酯 (DEHP) 和邻苯二甲酸二异壬酯 (DINP) 没有观察到影响，而邻苯二甲酸二丁酯 (DBP) 似乎对 hNIS 启动子有小丑般的调节作用。尽管 DIDP、BBP 和 DOP 对 NIS 基因转录的刺激作用不是很强，但这一发现非常重要，因为人类经常长期接触邻苯二甲酸酯增塑剂，其积累可能导致甲状腺功能亢进。 (c) 2005 Elsevier Ireland Ltd. 保留所有权利。
The diesters of benzene-1,2-dicarboxylic (phthalic) acid, the phthalates, are used to make plastics flexible and can comprise 40% of the weight of plastic. Human exposure to phthalates can occur via ingestion, inhalation and dermal routes, as well as through parenteral exposure from medical devices containing phthalates. Since earlier morphological studies showed that some phthalates induced thyroid hyperactivity, we thought it important to investigate possible effects of six major phthalates on the transcriptional activity of sodium/iodide symporter (NIS). Di-isodecyl phthalate (DIDP), benzyl butyl phthalate (BBP) and di-octyl phthalate (DOP) increased the activity of the human NIS promoter construct 2.5-, 2.6- and 2.4-fold, respectively. Likewise, these phthalates also enhanced the rat NIS endogenous mRNA expression ca. 2-fold. No effect was observed for bis-(2-ethylhexyl) phthalate (DEHP) and di-isononyl phthalate (DINP), whereas dibutyl phthalate (DBP) appeared to clown-regulate hNIS promoter. Although the demonstrated stimulation of NIS gene transcription by DIDP, BBP and DOP is not very strong, this finding is of great importance as humans are routinely exposed for long periods to phthalate plasticisers, the accumulation of which may contribute to thyroid hyperfunction. (c) 2005 Elsevier Ireland Ltd. All rights reserved.