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Reprod Toxicol ; 70: 116-125, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-27915012

RESUMO

Vasculogenesis and angiogenesis are the processes by which new blood vessels are formed. We have developed a serum-free human adipose stromal cell and umbilical cord vein endothelial cell based vasculogenesis/angiogenesis test. In this study, the test was validated in our GLP laboratory following the OECD Guidance Document 34 [1] using erlotinib, acetylic salicylic acid, levamisole, 2-methoxyestradiol, anti-VEGF, methimazole, and D-mannitol to show its reproducibility, repeatability, and predictivity for humans. The results were obtained from immunostained tubule structures and cytotoxicity assessment. The performance of the test was evaluated using 26 suspected teratogens and non-teratogens. The positive predictive value was 71.4% and the negative predictive value was 50.0%, indicating that inhibition of vasculogenesis is a significant mechanism behind teratogenesis. In conclusion, this test has great potential to be a screening test for prioritization purposes of chemicals and to be a test in a battery to predict developmental hazards in a regulatory context.


Assuntos
Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Células Estromais/efeitos dos fármacos , Teratogênicos/toxicidade , Testes de Toxicidade/métodos , 2-Metoxiestradiol , Tecido Adiposo/citologia , Aspirina/farmacologia , Células Cultivadas , Meios de Cultura , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Cloridrato de Erlotinib/farmacologia , Estradiol/análogos & derivados , Estradiol/farmacologia , Células Endoteliais da Veia Umbilical Humana/fisiologia , Humanos , Laboratórios , Levamisol/farmacologia , Manitol/farmacologia , Metimazol/farmacologia , Reprodutibilidade dos Testes , Soro , Células Estromais/fisiologia , Cordão Umbilical/citologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
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