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

  • Kim, Jeong-Ah (Department of Medicine and Physiology, University of Maryland) ;
  • Lee, Eun-Ju (Department of Biochemistry, College of Medicine, Ewha Womans University) ;
  • Chung, In Hye (Department of Biochemistry, College of Medicine, Ewha Womans University) ;
  • Kim, Hyung-Lae (Department of Biochemistry, College of Medicine, Ewha Womans University)
  • Published : 2004.06.01

Abstract

In a variety of animal species, the perinatal exposure of experimental animals to the 2,3,7,8-tetrachlorodibenzo­p-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 11 K oligonucleotide­microarray from the bone marrow cells of male C57BL/6J mice after an intraperitoneal injection of $1{\mu}g$ 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 $\pm$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.

Keywords

References

  1. Behnisch, P.A., Hosoe, K., and Sakai, S,-I. (2001). Combinatorial bio/chemical analysis of dioxin and dioxin-like compounds in waste recycling, feed/food, humans/wildlife and the environment Environment International 27, 495-519 https://doi.org/10.1016/S0160-4120(01)00029-0
  2. Behnisch, P.A., Hosoe, K., and Sakai, S.-I.. (2001). Bioanalytical screening methods for dioxins and dioxin-like compounds a review of bioassay/biomarker technology Environment International 27, 413-39 https://doi.org/10.1016/S0160-4120(01)00028-9
  3. Drahushuk, A.T., McGarrigIe, B.P., Slezak, B.P., Stegeman, J.J., and Olson, J.R. (1999). Time and concentration dependent induction of CYP1A1 and CYP1A2 in precision-cut rat liver slices incubated in dynamic organ culture in the presence of 2,3,7,8-tetrachlorodibenzop-dioxin. Toxicol. Appl. Pharmacol. 155,127-38 https://doi.org/10.1006/taap.1998.8578
  4. Fine, J.S., Gasiewicz, T.A., and Silverstone, A.E. (1989). Lymphocyte stem cell alterations following perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Mol. Pharmacol. 35, 18-25
  5. Gehrs, B.C., Riddle, M.M., Williams, W.C., and Smialowicz, R.J. (1997). Alteration in the developing immune system of the F344 rat after perinatal exposure to 2,3,7,8-TCDD. Effect on the fetus and the neonate. Toxicol, 122. 219-228 https://doi.org/10.1016/S0300-483X(97)00098-X
  6. Grassman, J.A., Masten, S.A., Walker, N.J., and Lucier, G.W. (1998). Animal models of human response to dioxins. Environ. Health Perspect. 106 (Suppl. 2), 761775 https://doi.org/10.2307/3433831
  7. Hollyday, S., Lindstrom, P., Blaylock, B., Comment-C.E., GermoIec-Dr, Heindell, J., and Luster, M. (1991). Perinatal thymocyte antigen expression and postnatal immune development altered by gestational exposure to TCDD. Teratol. 44, 385-393 https://doi.org/10.1002/tera.1420440405
  8. Kim, H.-L. (2003). Comparison of oligonucleotide-microarray and serial analysis of gene expression (SAGE) in transcript profiling analysis of megakaryocytes derived from CD34+ cells. Exp. Mol. Med. 35, 460-466 https://doi.org/10.1038/emm.2003.60
  9. Luster, M.L., Boorman, G.A., Dean, J.H., Harris, M.W., Luebke, R.W., Padarathsingh, M.L., and Moore, J.A (1980). Examination of bone marrow, immunologic parameters and host susceptibility following pre- and postnatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Int. J. Immunopharmacol. 2, 301-10 https://doi.org/10.1016/0192-0561(80)90030-2
  10. Martinez, J.M., Afshari, C.A., Bushel, P.R., Masuda, A., Takahashi, T., and Walker, N.J. (2002). Dlfferential toxicogenomic response to 2,3,7,8-TCDD in malignant and nonmalignant human airway epithelial cells. Toxicol. Sci. 69, 409-423 https://doi.org/10.1093/toxsci/69.2.409
  11. Murante, F.G. and Gasiewicz, T.A. (2000). Hemopoietic progenitor cells are sensitive targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin in C57BL/6J mice. Toxicol, Sci. 54, 374-83 https://doi.org/10.1093/toxsci/54.2.374
  12. Poland, A. and Knutson, J.C., (1982). 2,3,7,8-tetrachlorodibenzo pdioxin and related halogenated aromatic hydrocarbons: examination of the mechanism of toxicity. Annu. Rev. Pharmacol. Toxicol. 22, 517-554 https://doi.org/10.1146/annurev.pa.22.040182.002505
  13. Puga, A., Maie,r A., and Medvedovic, M. (2000). The transcriptional signature of dioxin in human hepatoma HepG2 cells. Biochem. Pharmacol. 60, 1129-1142 https://doi.org/10.1016/S0006-2952(00)00403-2
  14. Safe, S. (2001). MoIecuIar bioIogy of the Ah receptor and its role in carcinogenesis. Toxicol. Lett. 120, 1-7 https://doi.org/10.1016/S0378-4274(01)00301-0
  15. Sakai, R., Kajiume, T., Inoue, H., Kanno, R., Miyazaki, M., Ninomiya, Y., and Kanno, M. (2003). TCDD Treatment Eliminates the Long-Term Reconstitution Activity of Hematopoietic Stem Cells. Toxicol. Sci. 72, 84-91 https://doi.org/10.1093/toxsci/kfg002
  16. Tucker, A.N., Vore, S.J., and Luster, M.I. (1986). Suppression of B cell differentiation by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Mol. Pharmacol. 29, 372-7
  17. Yoon, B.I., Hirabayashi, Y., Ogawa, Y., Kanno, J., Inoue, T., and Kaneko, T. (2001). Hemopoietic cell kinetics after intraperitoneal single injection of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice. Chemosphere 43, 819-22 https://doi.org/10.1016/S0045-6535(00)00439-2
  18. Zeytun, A., McKaIIiP, R.J., Fisher, M., Camacho, I., Nagarkatti, M., and Nagarkatti, P.S. (2002). Analysis of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced gene expression profile in vivo using pathway-specific cDNA arrays. Toxicol. 178, 241-260 https://doi.org/10.1016/S0300-483X(02)00230-5