TY  - GEN
N2  - There is an increasing demand by regulators, pharmaceutical manufacturers and industry for reliable and ethically acceptable model systems to assess and predict the toxicity of pharmaceutical products, chemicals, and waste.  In particular, developmental toxicity of compounds has largely been ignored in the past raising massive concerns. While cell lines have great merits as test systems, they do not reflect the complexity of a developing embryo. Zebrafish and their embryos have been used in toxicity assays in the past and have a great potential for studying reproductive toxicity and the molecular basis of developmental toxicity. Toxicogenomics is a powerful tool for compound classification based on mechanistic studies, which could eventually lead to the prediction of the toxicity of novel compounds.  I have carried out here a systematic toxicogenomic study of zebrafish embryos with the aim to develop this system further as a model for molecular developmental toxicity studies. Questions such as stage- and compound specificity were addressed. The toxicogenomic responses to a series of 6 test compounds were highly stage-dependent. Moreover, exposure of late embryonic stages between 96 and 120 hours post-fertilisation induced transcriptional profiles that are characteristic for specific compounds. This leads to the identification of 199 genes that are induced by at least one of the 11 compounds including a number of signature genes that appear specific for individual compounds or compound groups within the set of chemicals investigated. Moreover, I have tested whether one can observe toxicogenomic responses in the absence of apparent morphological effects. In several instances robust gene responses were measured at concentrations that did not have obvious morphological effects. This raises hopes that toxicogenomic studies in the zebrafish embryo could be used to predict chronic effects of low level exposure. In situ hybridisation of a number of selected genes showed that the responses can be highly tissue restricted indicating that the whole mount protocol developed here is highly sensitive.    In conclusion, this toxicogenomic analysis, demonstrated that zebrafish embryos may be suitable to study the transcriptional responses to toxicants with high specificity and more sensitivity. The zebrafish may thus be developed into a system that will not only help to elucidate the molecular mechanisms of toxicity but may be also useful to predict the developmental toxicity of novel chemicals by comparison of toxicogenomic profiles.  
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/7676/
A1  - Yang, Lixin
KW  - Toxikogenomischertoxicogenomics 
KW  -  zebrafish embryo
ID  - heidok7676
Y1  - 2007///
TI  - Transcriptional Profiling Reveals Barcode-Like Toxicogenomic Responses In The Zebrafish Embryo
AV  - public
ER  -