Transcriptional profiling reveals barcode-like toxicogenomic responses in the zebrafish embryo

Microarray profiling of zebrafish embryos exposed to a range of environmental toxicants revealed distinct expression profiles for each of the toxicants tested

Toxicants induce similar morphological changes in 120 hpf zebrafish embryos

<p><b>Copyright information:</b></p><p>Taken from "Transcriptional profiling reveals barcode-like toxicogenomic responses in the zebrafish embryo"</p><p>http://genomebiology.com/2007/8/10/R227</p><p>Genome Biology 2007;8(10):R227-R227.</p><p>Published online 25 Oct 2007</p><p>PMCID:PMC2246301.</p><p></p> Embryos were treated with methylmercury chloride (60 μg/l, MeHg); CdCl(5 mg/l, Cd); PbCl(2.8 mg/l, Pb); AsO(79 mg/l, As); Aroclor 1254 (33 mg/l, PCB); acrylamide (71 mg/l, AA); tert-butylhydroquinone (1.7 mg/l, tBHQ); 4-chloroaniline (50 mg/l, 4CA); 1,1-bis-(4-chlorophenyl)2,2,2-trichloroethane (15 mg/l, DDT); 2,3,7,8-tetrachlorodibenzo-p-dioxin (500 ng/l, TCDD); valproic acid (50 mg/l, VA); vehicle 1 control (VC1): embryo water alone (for Cd, MeHg, Pb, As, VA, AA treatments); vehicle 2 control (VC2): 0.2% ethanol control (for 4CA, DDT, tBHQ, PCB); vehicle 3 control (VC3): 0.025% DMSO, 1.4 mg/l toluene (for TCDD). Embryos showed frequently a bent body axis and developed pericardial edema upon further cultivation

Distinct toxicogenomic expression profiles are induced by different toxicants

<p><b>Copyright information:</b></p><p>Taken from "Transcriptional profiling reveals barcode-like toxicogenomic responses in the zebrafish embryo"</p><p>http://genomebiology.com/2007/8/10/R227</p><p>Genome Biology 2007;8(10):R227-R227.</p><p>Published online 25 Oct 2007</p><p>PMCID:PMC2246301.</p><p></p> Principal component analysis of the toxicogenomic profiles derived from three different embryonic stages. Embryos were exposed to vehicle controls or to one of six chemicals for the periods 4-24 hpf (green), 24-48 hpf (blue), or 96-120 hpf (red). Circles, TCDD: 150 ng/l (24 hpf), 500 ng/l (48 hpf), 500 ng/l (120 hpf). Squares, MeHg: 50 μg/l (24 hpf), 60 μg/l (48 hpf), 60 μg/l (120 hpf). Triangles, VA: 15 mg/l (24 hpf), 50 mg/l (48 hpf), 50 mg/l (120 hpf). Crosses, 4CA: 15 mg/l (24 hpf), 50 mg/l (48 hpf), 50 mg/l (120 hpf). Asterisks, Cd 500 μg/l (24 hpf), 5 mg/l (48 hpf), 5 mg/l (120 hpf). Stars, DDT: 5 mg/l (24 hpf), 15 mg/l (48 hpf), 15 mg/l (120 hpf). While the transcriptional profiles of the 4-24 hpf treatment group (green symbols) cluster closely, characteristic gene-expression profiles were induced by the 24-48 hpf (blue symbols) and the 96-120 hpf (red symbols) exposures to each of the different toxicants. Venn diagram comparing the number of genes induced at the three stages by all six toxicants. Numbers indicate numbers of regulated or co-regulated genes at the different stages (more than 1.95-fold change and adjusted < 0.025)

The concentration dependence of toxicogenomic responses and the synergistic effects of low doses

<p><b>Copyright information:</b></p><p>Taken from "Transcriptional profiling reveals barcode-like toxicogenomic responses in the zebrafish embryo"</p><p>http://genomebiology.com/2007/8/10/R227</p><p>Genome Biology 2007;8(10):R227-R227.</p><p>Published online 25 Oct 2007</p><p>PMCID:PMC2246301.</p><p></p> Embryos were exposed to decreasing concentrations of Cd (a, lane 1, 5 mg/l: lane 2, 2.5 mg/l; lane 3, 0.5 mg/l), or MeHg (b, lane 1, 60 μg/l; lane 2, 30 μg/l; lane 3, 6 μg/l) or TCDD (c, lane 1, 500 ng/l; lane 2, 250 ng/l; lane 3, 50 ng/l). The low concentrations elicit significant changes in gene expression. Embryos were exposed either to 50 μg/l Cd (lane 1) or 6 μg/l MeHg (lane 2) or 7.9 mg/l As (lane 3) or 280 μg/l Pb (lane 4) alone, or to a mixture (Mix, lane 5) of Cd (50 μg/l), Pb (280 μg/l), MeHg (6 μg/l) and As (7.9 mg/l). The mixture shows a strongly increased response with respect to the degree of changes of expression of individual genes (dark red and dark blue bars). Arrowheads point to examples of synergistic responses whereas the dots highlight genes whose response seems to be additive. The square indicates a gene that was downregulated by As and slightly upregulated by the mixture. All exposures were performed between 96 and 120 hpf. The color key for fold changes in gene expression in (a-c) is indicated on the left and ranges from threefold upregulated (red) to threefold downregulated (blue). The color key for (d) is on the right and ranges from fivefold upregulated (red) to fivefold downregulated (blue). White bars indicate missing data. Only genes were listed whose mRNA levels changed by at least twofold (< 0.025) in at least one of the treatments. The data represent the average over all biological and technical repeats (see Table 1)