气候变化领域集成服务门户(CCPortal): Embryonic vascular disruption adverse outcomes: Linking high throughput signaling signatures with functional consequences

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DOI	10.1016/j.reprotox.2017.05.005
	Embryonic vascular disruption adverse outcomes: Linking high throughput signaling signatures with functional consequences
	Ellis-Hutchings, Robert G.1; Settivari, Raja S.1; McCoy, Alene T.1; Kleinstreuer, Nicole 2; Franzosa, Jill 3; Knudsen, Thomas B.3; Carney, Edward W.1
发表日期	2017-06-01
ISSN	0890-6238
卷号	70 页码:82-96
英文摘要	Embryonic vascular disruption is an important adverse outcome pathway (AOP) as chemical disruption of cardiovascular development induces broad prenatal defects. High throughput screening (HTS) assays aid AOP development although linking in vitro data to in vivo apical endpoints remains challenging. This study evaluated two anti-angiogenic agents, 5HPP-33 and TNP-470, across the ToxCastDB HTS assay platform and anchored the results to complex in vitro functional assays: the rat aortic explant assay (AEA), rat whole embryo culture (WEC), and the zebrafish embryotoxicity (ZET) assay. Both were identified as putative vascular disruptive compounds (pVDCs) in ToxCastDB and disrupted angiogenesis and embryo genesis in the functional assays. Differences were observed in potency and adverse effects: 5HPP-33 was embryolethal (WEC and ZET); TNP-470 produced caudal defects at lower concentrations. This study demonstrates how a tiered approach using HTS signatures and complex functional in vitro assays might be used to prioritize further in vivo developmental toxicity testing. (C) 2017 Elsevier Inc. All rights reserved.
英文关键词	5HPP-33;TNP-470;Embryo;Vascular disruption;ToxCast;Functional in vitro assay
语种	英语
WOS记录号	WOS:000403736500008
来源期刊	REPRODUCTIVE TOXICOLOGY
来源机构	美国环保署
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/58058
作者单位	1.Dow Chem Co USA, Toxicol & Environm Res & Consulting, 1803 Bldg, Midland, MI 48674 USA; 2.Interagency Ctr Evaluat Alternat Toxicol Methods, Natl Toxicol Program, Res Triangle Pk, NC 27711 USA; 3.US EPA, Natl Ctr Computat Toxicol, Off Res & Dev, Res Triangle Pk, NC 27711 USA
推荐引用方式 GB/T 7714	Ellis-Hutchings, Robert G.,Settivari, Raja S.,McCoy, Alene T.,et al. Embryonic vascular disruption adverse outcomes: Linking high throughput signaling signatures with functional consequences[J]. 美国环保署,2017,70:82-96.
APA	Ellis-Hutchings, Robert G..,Settivari, Raja S..,McCoy, Alene T..,Kleinstreuer, Nicole.,Franzosa, Jill.,...&Carney, Edward W..(2017).Embryonic vascular disruption adverse outcomes: Linking high throughput signaling signatures with functional consequences.REPRODUCTIVE TOXICOLOGY,70,82-96.
MLA	Ellis-Hutchings, Robert G.,et al."Embryonic vascular disruption adverse outcomes: Linking high throughput signaling signatures with functional consequences".REPRODUCTIVE TOXICOLOGY 70(2017):82-96.