Turan N, Waring R H, Ramsden D B
School of Biosciences, University of Birmingham, UK.
Mol Cell Endocrinol. 2005 Dec 1;244(1-2):15-9. doi: 10.1016/j.mce.2005.01.016. Epub 2005 Oct 11.
Sulphation is important in xenobiotic detoxification and in steroid and thyroid hormones synthesis, transport and metabolism. Potential endocrine disrupting actions of plasticisers were assessed by studying effects on cell viability, cell proliferation and expression of enzymes (cysteine dioxygenase, sulphite oxidase, PAPS synthase I and II) involved in the synthesis of the cofactor, PAPS, for steroid sulphotransferases. TE 671 cells were used to study the effects of exposure to alkylphenols and alkylphenolethoxylates, bisphenol A, bisphenol A methacrylate, alkyladipates, dialkyl phthalates and resorcinol. The lactate dehydrogenase assay and CellTiter 96) AQ(ueous) One Solution Cell Proliferation Assay were used to measure cytotoxicity and cell proliferation, respectively. Steady-state mRNA was assessed by semi-quantitative RT-PCR and real time RT-PCR. None of the compounds tested was cytotoxic in TE 671 cells, however, cell proliferation was significantly increased with 0.005-0.5 microM dioctyl phthalate, diisodecyl phthalate (DIP) and butylbenzyl phthalate (P<0.05, n = 4). Real time RT-PCR showed dose-dependent decreases in steady-state mRNA levels of all the enzymes studied (P<0.05, n = 4) with 0.005-0.5 microM octylphenol, bis (2-ethylhexyl) phthalate and DIP treatment. Endocrine disrupting effects of some plasticisers may be a consequence of modulation of expression of enzymes supplying PAPS for hormone sulphation.
硫酸化在异源物解毒以及类固醇和甲状腺激素的合成、运输与代谢过程中起着重要作用。通过研究增塑剂对细胞活力、细胞增殖以及参与合成类固醇磺基转移酶的辅因子3'-磷酸腺苷-5'-磷酸硫酸（PAPS）的酶（半胱氨酸双加氧酶、亚硫酸盐氧化酶、PAPS合酶I和II）表达的影响，评估了增塑剂潜在的内分泌干扰作用。采用TE 671细胞研究烷基酚和烷基酚聚氧乙烯醚、双酚A、甲基丙烯酸双酚A酯、己二酸酯、邻苯二甲酸二烷基酯和间苯二酚的暴露影响。乳酸脱氢酶测定法和CellTiter 96) AQ(ueous) One Solution细胞增殖测定法分别用于测量细胞毒性和细胞增殖。通过半定量逆转录聚合酶链反应（RT-PCR）和实时RT-PCR评估稳态mRNA。所测试的化合物在TE 671细胞中均无细胞毒性，然而，0.005 - 0.5微摩尔/升的邻苯二甲酸二辛酯、邻苯二甲酸二异癸酯（DIP）和邻苯二甲酸丁苄酯使细胞增殖显著增加（P<0.05，n = 4）。实时RT-PCR显示，用0.005 - 0.5微摩尔/升的辛基酚、邻苯二甲酸二（2-乙基己基）酯和DIP处理后，所有研究的酶的稳态mRNA水平呈剂量依赖性下降（P<0.05，n = 4）。一些增塑剂的内分泌干扰作用可能是调节为激素硫酸化提供PAPS的酶表达的结果。
