Effect-directed analysis of endocrine-disrupting compounds in multi-contaminated sediment: identification of novel ligands of estrogen and pregnane X receptors

被引:65
作者
Creusot, Nicolas [1 ,2 ,3 ]
Budzinski, Helene [2 ,3 ]
Balaguer, Patrick [4 ]
Kinani, Said [1 ]
Porcher, Jean-Marc [1 ]
Ait-Aissa, Selim [1 ]
机构
[1] INERIS, Unite Ecotoxicol In Vitro & In Vivo, F-60550 Verneuil En Halatte, France
[2] Univ Bordeaux, EPOC, UMR 5805, F-33405 Talence, France
[3] CNRS, EPOC, UMR 5805, F-33405 Talence, France
[4] INSERM, U896, CRLC, IRCM,UM1, F-34298 Montpellier, France
关键词
EDCs; Emerging pollutants; Multi-contaminated sediment; Multi-step fractionation; DIOXIN-LIKE; SEINE ESTUARY; WATER SAMPLES; REPORTER; ALPHA; PHARMACEUTICALS; PESTICIDES; CHEMICALS; BIOASSAYS; BINDING;
D O I
10.1007/s00216-013-6708-5
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Effect-directed analysis (EDA)-based strategies have been increasingly used in order to identify the causative link between adverse (eco-)toxic effects and chemical contaminants. In this study, we report the development and use of an EDA approach to identify endocrine-disrupting chemicals (EDCs) in a multi-contaminated river sediment. The battery of in vitro reporter cell-based bioassays, measuring estrogenic, (anti)androgenic, dioxin-like, and pregnane X receptor (PXR)-like activities, revealed multi-contamination profiles. To isolate active compounds of a wide polarity range, we established a multi-step fractionation procedure combining: (1) a primary fractionation step using normal phase-based solid-phase extraction (SPE), validated with a mixture of 12 non-polar to polar standard EDCs; (2) a secondary fractionation using reversed-phase-based high-performance liquid chromatography (RP-HPLC) calibrated with 33 standard EDCs; and (3) a purification step using a recombinant estrogen receptor (ER) affinity column. In vitro SPE and HPLC profiles revealed that ER and PXR activities were mainly due to polar to mid-polar compounds, while dioxin-like and anti-androgenic activities were in the less polar fractions. The overall procedure allowed final isolation and identification of new environmental PXR (e.g., di-iso-octylphthalate) and ER (e.g., 2,4-di-tert-butylphenol and 2,6-di-tert-butyl-alpha-methoxy-p-cresol) ligands by using gas chromatography coupled with mass spectrometry with full-scan mode acquisition in mid-polar fractions. In vitro biological activity of these chemicals was further confirmed using commercial standards, with di-iso-octylphthalate identified for the first time as a potent hPXR environmental agonist.
引用
收藏
页码:2553 / 2566
页数:14
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