Distinguishing mode of action of compounds inducing craniofacial malformations in zebrafish embryos to support dose-response modeling in combined exposures

Harm J. Heusinkveld,Willem G. Schoonen,Hennie M. Hodemaekers,Ananditya Nugraha, Jan-Jaap Sirks, Vivianne Veenma, Carina Sujan,Jeroen L.A. Pennings,Paul F. Wackers,Luca Palazzolo,Ivano Eberini,Emiel Rorije,Leo T.M. van der Ven

Reproductive Toxicology（2020）

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摘要

•Discernable gene expression profiles for MOAs of reference compounds.•GE profiles of unknown compounds can be matched with reference profiles.•MOAs were supported by ToxCast in vitro assays and by molecular docking.•qPCR proved a valuable tool for identification of compound MOAs.•Distinction of MOAs supports modeling of combined exposures.

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关键词

AhR,CAG,CED20,Cyp26,Cyp51,EFSA,EGF,HDAC,hpf,HPT-axis,MOA,MOE,PFOS,PPARα,qPCR,RA,RAR,RXR,TCDD,TGFbeta,TR,VPA

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