van den Dungen Myrthe W, Rijk Jeroen C W, Kampman Ellen, Steegenga Wilma T, Murk Albertinka J
Sub-department of Environmental Technology, Wageningen University, Bornse Weilanden 9, 6708 WG Wageningen, The Netherlands; Division of Human Nutrition, Wageningen University, Bomenweg 4, 6703 HD Wageningen, The Netherlands.
RIKILT - Institute of Food Safety, Wageningen UR, Akkermaalsbos 2, 6708 WB Wageningen, The Netherlands.
Toxicol In Vitro. 2015 Jun;29(4):769-78. doi: 10.1016/j.tiv.2015.03.002. Epub 2015 Mar 9.
Persistent organic pollutants (POPs) such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorobiphenyl (PCB) 126 and 153, perfluorooctanesulfonic acid (PFOS), hexabromocyclododecane (HBCD), 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), tributyltin (TBT), and methylmercury (MeHg) can be accumulated in seafood and then form a main source for human exposure. Some POPs have been associated with changes in steroid hormone levels in both humans and animals. This study describes the in vitro effects of these POPs and mixtures thereof in H295R adrenocortical carcinoma cells. Relative responses for 13 steroid hormones and 7 genes involved in the steroidogenic pathway, and CYP1A1, were analyzed. PFOS induced the most pronounced effects on steroid hormone levels by significantly affecting 9 out of 13 hormone levels measured, with the largest increases found for 17β-estradiol, corticosterone, and cortisol. Furthermore, TCDD, both PCBs, and TBT significantly altered steroidogenesis. Increased steroid hormone levels were accompanied by related increased gene expression levels. The differently expressed genes were MC2R, CYP11B1, CYP11B2, and CYP19A1 and changes in gene expression levels were more sensitive than changes in hormone levels. The POP mixtures tested showed mostly additive effects, especially for DHEA and 17β-estradiol levels. This study shows that some seafood POPs are capable of altering steroidogenesis in H295R cells at concentrations that mixtures might reach in human blood, suggesting that adverse health effects cannot be excluded.
持久性有机污染物（POPs），如2,3,7,8-四氯二苯并对二恶英（TCDD）、多氯联苯（PCB）126和153、全氟辛烷磺酸（PFOS）、六溴环十二烷（HBCD）、2,2',4,4'-四溴二苯醚（BDE-47）、三丁基锡（TBT）和甲基汞（MeHg），可在海产品中蓄积，进而成为人类接触的主要来源。一些持久性有机污染物与人类和动物体内类固醇激素水平的变化有关。本研究描述了这些持久性有机污染物及其混合物对H295R肾上腺皮质癌细胞的体外影响。分析了13种类固醇激素以及参与类固醇生成途径的7个基因和CYP1A1的相对反应。PFOS对类固醇激素水平的影响最为显著，在所检测的13种激素水平中有9种受到显著影响，其中17β-雌二醇、皮质酮和皮质醇的增幅最大。此外，TCDD、两种多氯联苯和TBT均显著改变了类固醇生成。类固醇激素水平的升高伴随着相关基因表达水平的增加。差异表达的基因有MC2R、CYP11B1、CYP11B2和CYP19A1，基因表达水平的变化比激素水平的变化更敏感。所测试的持久性有机污染物混合物大多表现为加和效应，尤其是对脱氢表雄酮和17β-雌二醇水平。本研究表明，一些海产品中的持久性有机污染物在人类血液中可能达到的混合物浓度下，能够改变H295R细胞中的类固醇生成，这表明不能排除对健康产生不良影响的可能性。
