Effects of Dioxin Exposed in Human by Using Radioactive cDNA Microarray

  • Ryu, Yeon-Mi (Department of Biochemistry & Molecular biology, Korea University medical college) ;
  • Kim, Ki-Nam (Department of Biochemistry & Molecular biology, Korea University medical college) ;
  • Kim, Hye-Won (Department of Biochemistry & Molecular biology, Korea University medical college) ;
  • Sohn, Sung-Hwa (Department of Biochemistry & Molecular biology, Korea University medical college) ;
  • Lee, Seung-Ho (Department of Biochemistry & Molecular biology, Korea University medical college) ;
  • Kim, Yu-Ri (Department of Biochemistry & Molecular biology, Korea University medical college) ;
  • Seo, Sang-Hui (Department of Biochemistry & Molecular biology, Korea University medical college) ;
  • Lee, Seung-Min (Department of Biochemistry & Molecular biology, Korea University medical college) ;
  • Lee, Eun-Il (Department of Preventive Medicine, Korea University Medical college) ;
  • Kim, Meyoung-Kon (Department of Biochemistry & Molecular biology, Korea University medical college)
  • Published : 2006.03.31

Abstract

2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD) are well known as the most toxic environmental compound in these days. Many researches are reported that dioxin produces multiple toxic effects, such as endocrine toxicity, reproductive toxicity, immunotoxicity and cancer. In this study, we carried to discover novel evidence for previously unknown gene expression patterns in human exposed to dioxin by using radioactive cDNA microarray. 548 workers who were divided into experimental and control groups according to their urinary Naphthol levels were enrolled in our study. Blood mRNA in human was isolated, and the gene expression profiles were analyzed by cDNA microarray. Gene expression analysis identified 52 genes which exhibited a significant change. In our study, most notably, genes involved in cell cycle, cell proliferation, signal transduction and apoptosis in human exposed to dioxin, such as CCND3, TSHR, and EFRN5, were up-regulated. In the current study, we observed gene expression of people that are exposed to dioxin using radioactive cDNA microarray. Through these results, we suggest when objects are exposed to toxic compounds, such as dioxin, the radioactive cDNA microarray may be using in sensitively detecting of cancerous change.

Keywords

References

  1. Kiukkonen, A. et al. Interference by 2, 3, 7, 8-tetrachlorodibenzo- p-dioxin with cultured mouse submandibular gland branching morphogenesis involves reduced epidermal growth factor receptor signaling. Toxicol Appl Pharmacol. 2005 Aug 24
  2. Oesch-Bartlomowicz, B. et al. Aryl hydrocarbon receptor activation by cAMP vs. dioxin: divergent signaling pathways. Proc Natl Acad Sci U S A 102, 9218-9223 (2005)
  3. Boverhof, D.R. et al. Temporal and dose-dependent hepatic gene expression patterns in mice provide new insights into TCDD-Mediated hepatotoxicity. Toxicol Sci. 85, 1048-1063 (2005) https://doi.org/10.1093/toxsci/kfi162
  4. Ahn, N.S. et al. Molecular mechanisms of the 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin-induced inverted Ushaped dose responsiveness in anchorage independent growth and cell proliferation of human breast epithelial cells with stem cell characteristics. Mutat Res. (2005). Jul. 25
  5. Heijne, W.H. et al. Profiles of metabolites and gene expression in rats with chemically induced hepatic necrosis. Toxicol Pathol. 33, 425-433 (2005) https://doi.org/10.1080/01926230590958146
  6. Jin, B., Kim, G., Park, D.W. & Ryu, D.Y. Microarray analysis of gene regulation in the Hepa1c1c7 cell line following exposure to the DNA methylation inhibitor 5-aza-2′-deoxycytidine and 2, 3, 7, 8-tetrachlorodibenzo- p-dioxin. Toxicol In Vitro 18, 659-664 (2004) https://doi.org/10.1016/j.tiv.2004.02.006
  7. Korkalainen, M., Tuomisto, J. & Pohjanvirta, R. Primary structure and inducibility by 2, 3, 7, 8-tetrachlorodibenzo- p-dioxin (TCDD) of aryl hydrocarbon receptor repressor in a TCDD-sensitive and a TCDDresistant rat strain. Biochem Biophys Res Commun. 27, 315(1), 123-131 (2004)
  8. Vogel, C.F., Zhao, Y., Wong, P., Young, N.F. & Matsumura, F. The use of c-src knockout mice for the identification of the main toxic signaling pathway of TCDD to induce wasting syndrome. J Biochem Mol Toxicol. 17, 305-315 (2003) https://doi.org/10.1002/jbt.10096
  9. Kim, H. et al. Assay of 2-naphthol in human urine by high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl. 12, 734(2), 211-217 (1999)
  10. DeRisi, J. et al. Use of a cDNA microarray to analyse gene expression patterns in human cancer. Nat Genet. 14, 457-460 (1996) https://doi.org/10.1038/ng1296-457
  11. Vawter, M.P. et al. Application of cDNA microarrays to examine gene expression differences in schizophrenia. Brain Res Bull. 15, 641-650 (2001)
  12. Tanaka, T.S. et al. Genome-wide expression profiling of mid-gestation placenta and embryo using a 15,000 mouse developmental cDNA microarray. Proc Natl Acad Sci U S A 1, 97(16), 9127-9132 (2000)
  13. Eisen, M.B., Spellman, P.T., Brown, P.O. & Botstein, D. Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci U S A 8, 95 (25),14863-14868 (1998)
  14. Pruneri, G. et al. Cyclin D3 immunoreactivity is an independent predictor of survival in laryngeal squamous cell carcinoma. Clin Cancer Res. 1, 11(1), 242- 248 (2005)
  15. Casanovas, O. et al. P38SAPK2 phosphorylates cyclin D3 at Thr-283 and targets it for proteasomal degradation. Oncogene 30, 23(45), 7537-7544 (2004)
  16. Chen, Q., Lin, J., Jinno, S. & Okayama, H. Overexpression of Cdk6-cyclin D3 highly sensitizes cells to physical and chemical transformation. Oncogene 20, 22(7), 992-1001 (2003)
  17. Iida, H. et al. Ephrin-A1 expression contributes to the malignant characteristics of {alpha}-fetoprotein producing hepatocellular carcinoma. Gut. 54, 843-851 (2005) https://doi.org/10.1136/gut.2004.049486
  18. Varelias, A. et al. Human osteosarcoma expresses specific ephrin profiles: implications for tumorigenicity and prognosis. Cancer 15, 95(4), 862-869 (2002)
  19. Brokken, L.J., Bakker, O., Wiersinga, W.M. & Prummel, M.F. Functional thyrotropin receptor expression in the pituitary folliculo-stellate cell line TtT/GF. Exp Clin Endocrinol Diabetes 113, 13-20 (2005) https://doi.org/10.1055/s-2004-830516
  20. Bernardin-Fried, F. et al. AML1/RUNX1 increases during G1 to S cell cycle progression independent of cytokine-dependent phosphorylation and induces cyclin D3 gene expression. J Biol Chem. 9, 279(15), 15678-15687 (2004)
  21. Manes, S. et al. CCR5 expression influences the progression of human breast cancer in a p53-dependent manner. J Exp Med. 3, 198(9), 1381-1389 (2003)
  22. Murphy, P.M. Chemokines and the molecular basis of cancer metastasis. N Engl J Med. 13, 345(11), 833- 835 (2001)
  23. Balkwill, F. & Mantovani, A. Inflammation and cancer: back to Virchow? Lancet. 17, 357(9255), 539- 945 (2001) https://doi.org/10.1016/S0140-6736(02)95081-6
  24. Homey, B., Muller, A. & Zlotnik, A. Chemokines: agents for the immunotherapy of cancer? Nat Rev Immunol. 2, 175-184 (2002) https://doi.org/10.1038/nri748
  25. Luboshits, G. et al. Elevated expression of the CC chemokine regulated on activation, normal T cell expressed and secreted (RANTES) in advanced breast carcinoma. Cancer Res. 15, 59(18), 4681-4687 (1999)
  26. Prest, S.J. et al. Chemokines induce the cellular migration of MCF-7 human breast carcinoma cells: subpopulations of tumour cells display positive and negative chemotaxis and differential in vivo growth potentials. Clin Exp Metastasis 17, 389-396 (1999) https://doi.org/10.1023/A:1006657109866
  27. Smith, C.I. et al. The Tec family of cytoplasmic tyrosine kinases: mammalian Btk, Bmx, Itk, Tec, Txk and homologs in other species. Bioessays 23, 436-446 (2001) https://doi.org/10.1002/bies.1062
  28. Satterthwaite, A.B. & Witte, O.N. The role of Bruton's tyrosine kinase in B-cell development and function: a genetic perspective. Immunol Rev. 75, 120-127 (2000)
  29. Li, T. et al. Constitutive membrane association potentiates activation of Bruton tyrosine kinase. Oncogene 18, 15(12), 1375-1383 (1997)
  30. Lindvall, J. & Islam, T.C. Interaction of Btk and Akt in B cell signaling. Biochem Biophys Res Commun. 24, 293(5), 1319-1326 (2002)
  31. Finkel, T. Redox-dependent signal transduction. FEBS Lett. 30, 476(1-2), 52-54 (2000)
  32. Finkel, T. & Holbrook, N.J. Oxidants, oxidative stress and the biology of ageing. Nature 9, 408(6809), 239-247 (2000) https://doi.org/10.1038/009239a0
  33. Tokarska-Schlattner, M., Wallimann, T. & Schlattner, U. Multiple interference of anthracyclines with mitochondrial creatine kinases: preferential damage of the cardiac isoenzyme and its implications for drug cardiotoxicity. Mol Pharmacol. 61, 516-523 (2002) https://doi.org/10.1124/mol.61.3.516
  34. Lim, S., Zou, Y. & Friedman, E. The transcriptional activator Mirk/Dyrk1B is sequestered by p38alpha/ beta MAP kinase. J Biol Chem. 277, 49438-49445 (2002) https://doi.org/10.1074/jbc.M206840200
  35. sHolmstrom, T.H. et al. MAPK/ERK signaling in activated T cells inhibits CD95/Fas-mediated apoptosis downstream of DISC assembly. Embo J. 16, 5418- 5428 (2000)
  36. Naderi, J., Hung, M. & Pandey, S. Oxidative stressinduced apoptosis in dividing fibroblasts involves activation of p38 MAP kinase and over-expression of Bax: resistance of quiescent cells to oxidative stress. Apoptosis 8, 91-100 (2003) https://doi.org/10.1023/A:1021657220843
  37. de Thonel, A. & Eriksson, J.E. Regulation of death receptors-Relevance in cancer therapies. Toxicol Appl Pharmacol. 1, 207(2 Suppl), 123-132 (2005)
  38. Castellino, A.M., Parker, G.J., Boronenkov, I.V., Anderson, R.A. & Chao, M.V. A novel interaction between the juxtamembrane region of the p55 tumor necrosis factor receptor and phosphatidylinositol-4- phosphate 5-kinase. J Biol Chem. 28, 272(9), 5861- 5870 (1997)
  39. Hu, P. et al. Molecular cloning and mapping of the brain-abundant B1gamma subunit of protein phosphatase 2A, PPP2R2C, to human chromosome 4p16. Genomics 1, 67(1), 83-86 (2000).
  40. Duong, L.T., Lakkakorpi, P., Nakamura, I. & Rodan, G.A. Integrins and signaling in osteoclast function. Matrix Biol. 19, 97-105 (2000) https://doi.org/10.1016/S0945-053X(00)00051-2
  41. Irby, R.B. & Yeatman, T.J. Role of Src expression and activation in human cancer. Oncogene 20, 19 (49), 5636-5642 (2000)
  42. Marini, M.G. et al. Cloning MafF by recognition site screening with the NFE2 tandem repeat of HS2: analysis of its role in globin and GCSl genes regulation. Blood Cells Mol Dis. 29, 145-158 (2002) https://doi.org/10.1006/bcmd.2002.0550
  43. Wasserman, W.W. & Fahl, W.E. Functional antioxidant responsive elements. Proc Natl Acad Sci U S A 13, 94(10), 5361-5366 (1997)
  44. Rushmore, T.H. & Pickett, C.B. Transcriptional regulation of the rat glutathione S-transferase Ya subunit gene. Characterization of a xenobiotic-responsive element controlling inducible expression by phenolic antioxidants. J Biol Chem. 25, 265(24), 14648-14653 (1990)
  45. Favreau, L.V. & Pickett, C.B. Transcriptional regulation of the rat NAD (P)H:quinone reductase gene. Identification of regulatory elements controlling basal level expression and inducible expression by planar aromatic compounds and phenolic antioxidants. J Biol Chem. 5, 266(7), 4556-4561 (1991)
  46. Alam, J. et al. Nrf2, a Cap'n'Collar transcription factor, regulates induction of the heme oxygenase-1 gene. J Biol Chem. 10, 274(37), 26071-26078 (1999)
  47. Chen, L. et al. Ssdp proteins interact with the LIM-domain- binding protein Ldb1 to regulate development. Proc Natl Acad Sci U S A 29, 99(22), 14320-14325 (2002)
  48. Grassadonia, A. et al. 90K (Mac-2 BP) and galectins in tumor progression and metastasis. Glycoconj J. 19 (7-9), 551-556 (2004) https://doi.org/10.1023/B:GLYC.0000014085.00706.d4
  49. Ueda, S., Kuwabara, I. & Liu, F.T. Suppression of tumor growth by galectin-7 gene transfer. Cancer Res. 15, 64(16), 5672-5676 (2004)
  50. Oakes, G.H. & Bend, J.R. Early steps in bilirubinmediated apoptosis in murine hepatoma (Hepa 1c1c7) cells are characterized by aryl hydrocarbon receptorindependent oxidative stress and activation of the mitochondrial pathway. J Biochem Mol Toxicol. 19, 244-255 (2005)
  51. Baylin, S. & Bestor, T.H. Altered methylation patterns in cancer cell genomes: cause or consequence? Cancer Cell. 1, 299-305 (2002) https://doi.org/10.1016/S1535-6108(02)00061-2
  52. Kim, J.H. et al. Susceptibility of cholangiocarcinoma cells to parthenolide-induced apoptosis. Cancer Res. 15, 65(14), 6312-6320 (2005)
  53. Fu, G.F. et al. RNA Interference Remarkably Suppresses bcl-2 Gene Expression in Cancer Cells in Vitro and in Vivo. Cancer Biol Ther. 6, 4(8) (2005)
  54. Kim, K.M., Song, J.J., An, J.Y., Kwon, Y.T. & Lee, Y.J. Pretreatment of acetyl salicylic acid promotes trail-induced apoptosis by downregulating BCL-2 gene expression. J Biol Chem. 30 (2005)
  55. Vezina, C.M., Walker, N.J. & Olson, J.R. Subchronic exposure to TCDD, PeCDF, PCB126, and PCB153: effect on hepatic gene expression. Environ Health Perspect. 112, 1636-1644 (2004) https://doi.org/10.1289/ehp.7253
  56. Schmidt, C.K. et al. 2, 3, 7, 8-tetrachlorodibenzo-pdioxin (TCDD) alters the endogenous metabolism of all-trans-retinoic acid in the rat. Arch Toxicol. 77, 371-383 (2003) https://doi.org/10.1007/s00204-003-0457-8
  57. Volz, D.C., Bencic, D.C., Hinton, D.E., Law, J.M. & Kullman, S.W. 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD) induces organ- specific differential gene expression in male Japanese medaka (Oryzias latipes). Toxicol Sci. 85, 572-584 (2005) https://doi.org/10.1093/toxsci/kfi109
  58. Mimura, J. & Fujii-Kuriyama Y. Functional role of AhR in the expression of toxic effects by TCDD. Biochim Biophys Acta. 17, 1619(3), 263-268 (2003)
  59. Vrana, K.E., Freeman, W.M. & Aschner, M. Use of microarray technologies in toxicology research. Neurotoxicology 24, 321-332 (2003) https://doi.org/10.1016/S0161-813X(02)00193-6