TY - JOUR
T1 - Identification of vascular disruptor compounds by analysis in zebrafish embryos and mouse embryonic endothelial cells
AU - McCollum, Catherine W.
AU - Conde-Vancells, Javier
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
N1 - Funding Information:
We thank Sharanya Maanasi Kalasekar for help with making figures. This work was supported by grants from the Environmental Protection Agency (grant numbers R834289 and R83516301), the National Institute of Environmental Health Sciences of the National Institutes of Health (grant number P30ES023512 and contract number HHSN273201500010C), the Robert A Welch Foundation (grant number E-0004) and the Emerging Technology Fund of Texas under Agreement300-9-1958. The content is solely the responsibility of the authors and does not necessarily reflect the views of the funding agencies.
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2017/6
Y1 - 2017/6
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Mouse endothelial cells
KW - Vascular development
KW - Vascular disruptor compounds
KW - Zebrafish
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U2 - 10.1016/j.reprotox.2016.11.005
DO - 10.1016/j.reprotox.2016.11.005
M3 - Article
C2 - 27838387
AN - SCOPUS:85006847195
VL - 70
SP - 60
EP - 69
JO - Reproductive Toxicology
JF - Reproductive Toxicology
SN - 0890-6238
ER -