Analysis of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced gene expression profile in vivo using pathway-specific cDNA arrays

In the current study, we used pathway-specific cDNA arrays to detect the transcriptional signature induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in vivo by studying simultaneously the expression profiles of 83 genes involved in apoptosis, cytokine production and angiogenesis. To this end, C57BL/6 mice were injected i.p. with 50 mug/kg body weight of TCDD and 1 or 3 days later, the thymus was analyzed for gene expression profiles. In the thymus, 23 out of 37 apoptotic genes screened were up-regulated by TCDD by a factor of two or more when compared to the vehicle-treated controls. In contrast, in the spleen, 20 out of 22 and in the liver, 16 out of 37 apoptotic genes were up-regulated. IN the thymus, several genes encoding caspases, and members of the TNF family, including Fas ligand, were induced. Also, in the thymus, eight out of 23, and in the spleen, six out of 23 cytokine genes were up-regulated. In the liver and to a lesser extent in the thymus, certain angiogenesis genes were induced while others were repressed. When mice were injected with 0.1, 1, 10 or 50 mug/kg body weight of TCDD and the thymus was analyzed for apoptotic genes 1 day later, a dose-dependent response was not seen with most apoptotic genes. However, certain apoptotic genes were induced in the the thymus even at low doses of 01. mug/kg body weight of TCDD. These data demonstrate that TCDD alters the expression of a large array of genes involved in apoptosis, cytokine production and angiogenesis. Thus, pathway-specific cDNA arrays may help in the identification of specific gene expression profiles induced by xenobiotics and to delineate the molecular mechanisms of toxicity.