Identification of the Marker-Genes for Dioxin(2,3,7,8-tetradibenzo-p-dioxin)-Induced Immune Dysfunction by Using the High-Density Oligonucleotide Microarray

ABSTRACT

In a variety of animal species, the perinatal exposure of experimental animals to the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to the immune dysfunction, which is more severe and persistent than that caused by adult exposure. We report here the changes of gene expression and the identification of the marker-genes representing the dioxin exposure. The expressions of the transcripts were analyzed using the 11K oligonucleotide- microarray from the bone marrow cells of male C57BL/6J mice after an intraperitoneal injection of 1 microgram TCDD/kg body weight at various time intervals gestational 6.5 day(G6.5), 13.5 day(G13.5), 18.5 day(G18.5), and postnatal 3 (P3W)and 6 week (P6W). The type of self-organizing maps(SOM) representing the specific exposure dioxin could be identified as follows; G6.5D(C14), G13.5D(C0, C5, C10, C18), G18.5D(7), P3W(C2, C21), and P6W(C4, C15, C20). The candidate marker-genes were restricted to the transcripts, which could be consistently expressed greater than +/-2-fold in three experiments. The resulting candidates were 85 genes, the characteristics of that were involved in cell physiology and cell functions such as cell proliferation and immune function. We identified the biomarker-genes for dioxin exposure smc -like 2 from SOM C14 for the dioxin exposure at G6.5D, focal adhesion kinase and 6 other genes from C0, and protein tyrosine phosphatase 4a2 and 3 other genes from C5 for G13.5D, platelet factor 4 from C7 for G18.5D, fos from C2 for P3W.