Identification of vascular disruptor compounds by analysis in zebrafish embryos and mouse embryonic endothelial cells

Catherine W. McCollum; Javier Conde-Vancells; Charu Hans; Mercedes Vazquez-Chantada; Nicole Kleinstreuer; Tamara Tal; Thomas Knudsen; Shishir S. Shah; Fatima A. Merchant; Richard H. Finnell; Jan Åke Gustafsson; Robert Cabrera; Maria Bondesson

doi:10.1016/j.reprotox.2016.11.005

Identification of vascular disruptor compounds by analysis in zebrafish embryos and mouse embryonic endothelial cells

Catherine W. McCollum, Javier Conde-Vancells, Charu Hans, Mercedes Vazquez-Chantada, Nicole Kleinstreuer, Tamara Tal, Thomas Knudsen, Shishir S. Shah, Fatima A. Merchant, Richard H. Finnell, Jan Åke Gustafsson, Robert Cabrera, Maria Bondesson

Houston Methodist

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

To identify vascular disruptor compounds (VDCs), this study utilized an in vivo zebrafish embryo vascular model in conjunction with a mouse endothelial cell model to screen a subset of the U.S. Environmental Protection Agency (EPA) ToxCast Phase I chemical inventory. In zebrafish, 161 compounds were screened and 34 were identified by visual inspection as VDCs, of which 28 were confirmed as VDCs by quantitative image analysis. Testing of the zebrafish VDCs for their capacity to inhibit endothelial tube formation in the murine yolk-sac-derived endothelial cell line C166 identified 22 compounds that both disrupted zebrafish vascular development and murine endothelial in vitro tubulogenesis. Putative molecular targets for the VDCs were predicted using EPA's Toxicological Prioritization Index tool and a VDC signature based on a proposed adverse outcome pathway for developmental vascular toxicity.

Original language	English (US)
Pages (from-to)	60-69
Number of pages	10
Journal	Reproductive Toxicology
Volume	70
DOIs	https://doi.org/10.1016/j.reprotox.2016.11.005
State	Published - Jun 2017

Keywords

Angiogenesis
Mouse endothelial cells
Vascular development
Vascular disruptor compounds
Zebrafish

ASJC Scopus subject areas

Toxicology

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10.1016/j.reprotox.2016.11.005

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McCollum, C. W., Conde-Vancells, J., Hans, C., Vazquez-Chantada, M., Kleinstreuer, N., Tal, T., Knudsen, T., Shah, S. S., Merchant, F. A., Finnell, R. H., Gustafsson, J. Å., Cabrera, R., & Bondesson, M. (2017). Identification of vascular disruptor compounds by analysis in zebrafish embryos and mouse embryonic endothelial cells. Reproductive Toxicology, 70, 60-69. https://doi.org/10.1016/j.reprotox.2016.11.005

McCollum, CW, Conde-Vancells, J, Hans, C, Vazquez-Chantada, M, Kleinstreuer, N, Tal, T, Knudsen, T, Shah, SS, Merchant, FA, Finnell, RH, Gustafsson, JÅ, Cabrera, R & Bondesson, M 2017, 'Identification of vascular disruptor compounds by analysis in zebrafish embryos and mouse embryonic endothelial cells', Reproductive Toxicology, vol. 70, pp. 60-69. https://doi.org/10.1016/j.reprotox.2016.11.005

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title = "Identification of vascular disruptor compounds by analysis in zebrafish embryos and mouse embryonic endothelial cells",

abstract = "To identify vascular disruptor compounds (VDCs), this study utilized an in vivo zebrafish embryo vascular model in conjunction with a mouse endothelial cell model to screen a subset of the U.S. Environmental Protection Agency (EPA) ToxCast Phase I chemical inventory. In zebrafish, 161 compounds were screened and 34 were identified by visual inspection as VDCs, of which 28 were confirmed as VDCs by quantitative image analysis. Testing of the zebrafish VDCs for their capacity to inhibit endothelial tube formation in the murine yolk-sac-derived endothelial cell line C166 identified 22 compounds that both disrupted zebrafish vascular development and murine endothelial in vitro tubulogenesis. Putative molecular targets for the VDCs were predicted using EPA's Toxicological Prioritization Index tool and a VDC signature based on a proposed adverse outcome pathway for developmental vascular toxicity.",

keywords = "Angiogenesis, Mouse endothelial cells, Vascular development, Vascular disruptor compounds, Zebrafish",

author = "McCollum, {Catherine W.} and Javier Conde-Vancells and Charu Hans and Mercedes Vazquez-Chantada and Nicole Kleinstreuer and Tamara Tal and Thomas Knudsen and Shah, {Shishir S.} and Merchant, {Fatima A.} and Finnell, {Richard H.} and Gustafsson, {Jan {\AA}ke} and Robert Cabrera and Maria Bondesson",

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year = "2017",

month = jun,

doi = "10.1016/j.reprotox.2016.11.005",

language = "English (US)",

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AU - McCollum, Catherine W.

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AU - Hans, Charu

AU - Vazquez-Chantada, Mercedes

AU - Kleinstreuer, Nicole

AU - Tal, Tamara

AU - Knudsen, Thomas

AU - Shah, Shishir S.

AU - Merchant, Fatima A.

AU - Finnell, Richard H.

AU - Gustafsson, Jan Åke

AU - Cabrera, Robert

AU - Bondesson, Maria

PY - 2017/6

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KW - Angiogenesis

KW - Mouse endothelial cells

KW - Vascular development

KW - Vascular disruptor compounds

KW - Zebrafish

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Identification of vascular disruptor compounds by analysis in zebrafish embryos and mouse embryonic endothelial cells

Abstract

Keywords

ASJC Scopus subject areas

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