Identification of vascular disruptor compounds by analysis in zebrafish embryos and mouse embryonic endothelial cells.
Reprod Toxicol
; 70: 60-69, 2017 06.
Article
en En
| MEDLINE
| ID: mdl-27838387
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.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Sistema Cardiovascular
/
Células Endoteliales
/
Desarrollo Embrionario
/
Contaminantes Ambientales
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Reprod Toxicol
Asunto de la revista:
EMBRIOLOGIA
/
MEDICINA REPRODUTIVA
/
TOXICOLOGIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos