Figure 6

The concentration dependence of toxicogenomic responses and the synergistic effects of low doses. (a-c) 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. (d) 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 (p_adj < 0.025) in at least one of the treatments. The data represent the average over all biological and technical repeats (see Table 1).