Zebrafish (Danio rerio) embryos as a model for testing proteratogens
| Autor: | Nicole Huebler, Thomas H. Broschard, Ruben Strecker, Thomas Braunbeck, Stefan Weigt |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Aflatoxin B1
animal structures Danio Trimethadione Pharmacology Toxicology Cinnarizine Andrology medicine Animals Ifosfamide Cyclophosphamide Zebrafish Ovum Tegafur EC50 Dose-Response Relationship Drug biology Mutagenicity Tests Embryo Carbamazepine 2-Acetylaminofluorene biology.organism_classification Piracetam Teratology In vitro Drug Combinations Teratogens embryonic structures Thiotepa medicine.drug |
| Zdroj: | Toxicology. 281:25-36 |
| ISSN: | 0300-483X |
| DOI: | 10.1016/j.tox.2011.01.004 |
| Popis: | Zebrafish embryos have been shown to be a useful model for the detection of direct acting teratogens. This communication presents a protocol for a 3-day in vitro zebrafish embryo teratogenicity assay and describes results obtained for 10 proteratogens: 2-acetylaminofluorene, benzo[a]pyrene, aflatoxin B1, carbamazepine, phenytoin, trimethadione, cyclophosphamide, ifosfamide, tegafur and thio-TEPA. The selection of the test substances accounts for differences in structure, origin, metabolism and water solubility. Apart from 2-acetylaminofluorene, which mainly produces lethal effects, all proteratogens tested were teratogenic in zebrafish embryos exposed for 3 days. The test substances and/or the substance class produced characteristic patterns of fingerprint endpoints. Several substances produced effects that could be identified already at 1 dpf (days post fertilization), whereas the effects of others could only be identified unambiguously after hatching at ≥3 dpf. The LC50 and EC50 values were used to calculate the teratogenicity index (TI) for the different substances, and the EC20 values were related to human plasma concentrations. Results lead to the conclusion that zebrafish embryos are able to activate proteratogenic substances without addition of an exogenous metabolic activation system. Moreover, the teratogenic effects were observed at concentrations relevant to human exposure data. Along with other findings, our results indicate that zebrafish embryos are a useful alternative method for traditional teratogenicity testing with mammalian species. |
| Databáze: | OpenAIRE |
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