PUBLICATION
An information-rich, alternative, chemicals testing strategy using a high definition toxicogenomics and zebrafish (Danio rerio) embryos
- Authors
- Sawle, A.D., Wit, E., Whale, G., and Cossins, A.R.
- ID
- ZDB-PUB-100820-6
- Date
- 2010
- Source
- Toxicological sciences : an official journal of the Society of Toxicology 118(1): 128-139 (Journal)
- Registered Authors
- Cossins, Andy
- Keywords
- Toxicogenomics, microarray, zebrafish, dichloroaniline, pentachlorophenol, cadmium chloride, dichlorophenol
- Datasets
- GEO:GSE21680
- MeSH Terms
-
- Aniline Compounds/toxicity
- Animal Use Alternatives*
- Animals
- Cadmium Chloride/toxicity
- Chlorophenols/toxicity
- Embryo, Nonmammalian/chemistry
- Embryo, Nonmammalian/drug effects*
- Embryo, Nonmammalian/physiology
- Female
- Gene Expression Profiling
- Gene Expression Regulation/drug effects*
- Male
- Oligonucleotide Array Sequence Analysis
- Pentachlorophenol/toxicity
- Toxicity Tests/methods*
- Toxicogenetics
- Water Pollutants/toxicity*
- Xenobiotics/toxicity*
- Zebrafish/physiology*
- PubMed
- 20702589 Full text @ Toxicol. Sci.
Citation
Sawle, A.D., Wit, E., Whale, G., and Cossins, A.R. (2010) An information-rich, alternative, chemicals testing strategy using a high definition toxicogenomics and zebrafish (Danio rerio) embryos. Toxicological sciences : an official journal of the Society of Toxicology. 118(1):128-139.
Abstract
Large-scale toxicogenomic screening approaches offer great promise for generating a bias-free, system-wide view of toxicological effects and modes-of-action of chemicals and ecotoxicants. However, early applications of microarray technology have identified relatively small groups of responding genes with which to define new targets for analysis by conventional means. We have trialled a more intensive approach to the design and interpretation of array experiments incorporating a balanced interwoven ANOVA design with higher levels of biological replication, a more thorough analysis of errors and false discovery rates, and an analysis of response patterns using gene network models. Zebrafish embryos were exposed from 1.5 hours post-fertilisation for 72 hours to ecotoxicants representing different classes - 2,4-dichlorophenol, 3,4-dichloroaniline, pentachlorophenol, and cadmium chloride - at low concentrations producing a developmental disturbance to 10% of embryos, and half of this dose. Extracted whole embryo RNA was then analysed on microarrays. Analysis revealed responses of 3000-5000 genes, which is 10-1000 times greater than previously reported, with significance at lower levels of fold-change. Some gene responses were common to multiple toxicants and others were restricted to just one or two toxicants. The gene expression profiles for the different toxicants were distinctive, and analysis using network-based models provided a high level of detail of affected processes, some of which were novel. This approach provides a more highly refined view of toxic effects, from which meaningful patterns of response can be discerned and related to functional deficits, and from which more reliable indicators of toxicological effect can be predicted.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping