The role of cyp1a and heme oxygenase 1 gene expression for the toxicity of 3,4-dichloroaniline in zebrafish (Danio rerio) embryos.

Expression profiling of exposed cells or organisms can reveal genes sensitive to environmental contaminants or toxic compounds. However, the mechanistic relevance of altered gene expression often remains to be elucidated. Toxicant-dependent differential gene expression may indicate protection to or mediation of toxicity. Previous studies revealed a number of differentially transcribed genes in zebrafish embryos exposed to the model compound 3,4-dichloroaniline (3,4-DCA). To evaluate the significance of two of the most sensitive genes, cytochrome P 450 1a (cyp1a) and heme oxygenase 1 (hmox1), for 3,4-DCA toxicity, RNA interference-mediated knockdown and overexpression studies have been conducted. Knockdown of gene transcription by siRNA for cyp1a and hmox1 enhanced the frequency of developmental disorders in embryos exposed to 3,4-DCA. Vice versa, injection of cyp1a and hmox1 mRNA reduced the number of disorders. The opposite effects of siRNA and mRNA injection clearly indicate a protective role of the corresponding proteins. Functional studies such as the one presented could be applied to a wide variety of genes. They would be ideally suited to study the role of genes identified from toxicogenomic studies in the zebrafish embryo model.