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氟代二碘烷在 MCF-7 细胞、H295R 细胞和斑马鱼胚胎试验中的雌激素效应。

Estrogenic effects of fluorinated diiodine alkanes in MCF-7 cells, H295R cells and zebrafish embryo assays.

机构信息

National Shanghai Center for New Drug Safety Evaluation and Research, China State Institute of Pharmaceutical Industry, Shanghai, 201203, China.

出版信息

J Appl Toxicol. 2019 Jul;39(7):945-954. doi: 10.1002/jat.3783. Epub 2019 Mar 4.

Abstract

Fluorinated diiodine alkanes (FDIAs), important industrial intermediates in the synthesis of various perfluorinated compounds, which are distributed widely in wildlife and humans. Recent studies showed that FDIAs had in vitro estrogenic effects. However, to date, little information is available regarding the in vivo estrogenic effects of FDIAs and the mechanisms are unclear. In this study, a combination of in vitro and in vivo assays was used to investigate the estrogenic effects of FDIAs. We tested the in vitro estrogenic effects and estrogen receptor-related gene expression via MCF-7 cell assay. The hormone level of estradiol and the expression of estrogenic synthesis genes were measured in the H295R cell assay. Finally, the in vivo effects of FDIAs on development and estrogen-related gene expression were assessed in the zebrafish embryos assay. The results demonstrated that FDIAs could exhibit estrogenic activity through inducing cell proliferation (1.6-6.7-fold of the control) and estrogen receptor alpha gene expression (1.07-1.39-fold of the control), altering estradiol production (1.14-1.22-fold of the control) and the major estrogenic synthesis gene expression of CYP19 (1.22-1.31-fold of the control), disrupting the estrogen-related genes (esr1 and cyp19b) levels in zebrafish (1.52-2.99-fold and 2.95-5.00-fold of the control for esr1 and cyp19b, respectively). The current findings indicated the potential estrogenic effects of FDIAs and provided novel information for human risk assessment.

摘要

全氟碘烷(FDIAs)是各种全氟化合物合成中的重要工业中间体,广泛分布于野生动物和人类体内。最近的研究表明,FDIAs 具有体外雌激素效应。然而,迄今为止,关于 FDIAs 的体内雌激素效应及其机制的信息很少。在这项研究中,采用体外和体内相结合的方法来研究 FDIAs 的雌激素效应。我们通过 MCF-7 细胞检测来检测 FDIAs 的体外雌激素效应和雌激素受体相关基因表达。通过 H295R 细胞检测来测量雌二醇激素水平和雌激素合成基因的表达。最后,通过斑马鱼胚胎检测来评估 FDIAs 对发育和雌激素相关基因表达的体内影响。结果表明,FDIAs 可以通过诱导细胞增殖(对照的 1.6-6.7 倍)和雌激素受体α基因表达(对照的 1.07-1.39 倍)、改变雌二醇的产生(对照的 1.14-1.22 倍)和主要雌激素合成基因 CYP19 的表达(对照的 1.22-1.31 倍)来发挥雌激素活性,干扰斑马鱼中雌激素相关基因(esr1 和 cyp19b)的水平(esr1 和 cyp19b 分别为对照的 1.52-2.99 倍和 2.95-5.00 倍)。这些发现表明 FDIAs 具有潜在的雌激素效应,并为人类风险评估提供了新的信息。

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