PUBLICATION
Zebrafish (Danio rerio) embryos as a model for testing proteratogens
- Authors
- Weigt, S., Huebler, N., Strecker, R., Braunbeck, T., and Broschard, T.H.
- ID
- ZDB-PUB-110119-37
- Date
- 2011
- Source
- Toxicology 281(1-3): 25-36 (Journal)
- Registered Authors
- Braunbeck, Thomas
- Keywords
- Zebrafish, Metabolic activation, Proteratogen, Teratogenic, Embryotoxic
- MeSH Terms
-
- 2-Acetylaminofluorene/toxicity
- Aflatoxin B1/toxicity
- Animals
- Carbamazepine/toxicity
- Cinnarizine/toxicity
- Cyclophosphamide/toxicity
- Dose-Response Relationship, Drug
- Drug Combinations
- Ifosfamide/toxicity
- Mutagenicity Tests/methods*
- Ovum/drug effects
- Piracetam/toxicity
- Tegafur/toxicity
- Teratogens/toxicity*
- Thiotepa/toxicity
- Trimethadione/toxicity
- Zebrafish*/embryology
- PubMed
- 21237239 Full text @ Toxicology
- CTD
- 21237239
Citation
Weigt, S., Huebler, N., Strecker, R., Braunbeck, T., and Broschard, T.H. (2011) Zebrafish (Danio rerio) embryos as a model for testing proteratogens. Toxicology. 281(1-3):25-36.
Abstract
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 B(1), 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 LC(50) and EC(50) values were used to calculate the teratogenicity index (TI) for the different substances, and the EC(20) 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping