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

Research output: Contribution to journalArticle

6 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. In conclusion, our screening approach identified 22 novel VDCs, some of which were active at nanomolar concentrations

Original languageEnglish (US)
Pages (from-to)60-69
Number of pages10
JournalReproductive Toxicology
Volume70
DOIs
StatePublished - Jun 2017

Keywords

  • Angiogenesis
  • Mouse endothelial cells
  • Vascular development
  • Vascular disruptor compounds
  • Zebrafish

ASJC Scopus subject areas

  • Toxicology

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