Gene Expression Patterns of Spleen, Lung and Brain with Different Radiosensitivity in C57BL6 Mice

  • Majumder Md. Zahidur Rahman (Laboratory of Radiation Effect, Korea Institute of Radiological and Medical Sciences) ;
  • Lee, Woo-Jung (Laboratory of Radiation Effect, Korea Institute of Radiological and Medical Sciences) ;
  • Lee, Su-Jae (Laboratory of Radiation Experimental Therapeutics, Korea Institute of Radiological and Medical Sciences) ;
  • Bae, Sang-Woo (Laboratory of Radiation Effect, Korea Institute of Radiological and Medical Sciences) ;
  • Lee, Yun-Sil (Laboratory of Radiation Effect, Korea Institute of Radiological and Medical Sciences)
  • Published : 2005.12.30

Abstract

Although little information is available on the underlying mechanisms, various genetic factors have been associated with tissue-specific responses to radiation. In the present study, we explored the possibility whether organ specific gene expression is associated with radiosensitivity using samples from brain, lung and spleen. We examined intrinsic expression pattern of 23 genes in the organs by semi-quantitative RT-PCR method using both male and female C57BL/6 mice. Expression of p53 and p21, well known factors for governing sensitivity to radiation or chemotherapeutic agents, was not different among the organ types. Both higher expression of sialyltransferase, delta7-sterol reductase, leptin receptor splice variant form 12.1, and Cu/Zn superoxide dismutase (SOD) and lower expression of alphaB crystalline were specific for spleen tissue. Expression level of glutathione peroxidase and APO-1 cell surface antigen gene in lung tissue was high, while that of Na, K-ATPase alpha-subunit, Cu/ZnSOD, and cyclin G was low. Brain, radioresistant organ, showed higher expressions of Na, K-ATPase-subunit, cyclin G, and nucleolar protein hNop56 and lower expression of delta7-sterol reductase. The result revealed a potential correlation between gene expression patterns and organ sensitivity, and Identified genes which might be responsible for organ sensitivity.

References

  1. M.A. Kadhim, D.A. Macdonald, S.A. Goodhead, S.A. Lorimore, S.J. Marsden and E.G. Wright, 'Transmission of chromosomal instability after plutonium alpha particle irradiation,' Nature, 355, 738-740(1992) https://doi.org/10.1038/355738a0
  2. M.A. Kadhim, S.A. Lorimore, K.M.S. Townsend, D.T. Goodhead, V.J. Buckle and E.G.. Wright, 'Radiation-induced genomic instability delayed cytogenetic aberrations and apoptosis in primary human bone marrow cells,' Int. J. Radiat. Biol, 57, 287-293(1995)
  3. W.F. Morgan, J.P. Day, M.I. Kaplan, E.M. JcGee and C.L. Limoli, 'Genomic instability induced by ionizing radiation,' Radiat. Res., 146, 247-258(1996) https://doi.org/10.2307/3579454
  4. F. Lyng, S. O'Reilly, D. Cottell, C.B. Seymour and C. Mothersill, 'Persistent expression of morphological abnormalities in the distant progeny of irradiated cell,' Radiat. Environ. Biophys., 35, 273-283(1996) https://doi.org/10.1007/s004110050040
  5. M.S. Mendonca, T.M. Temples, D.L. Farrington and C. Bloch, 'Evidence for a role of delayeddeath and genomic instability in radiation induced neoplastic transformation of human hybrid cells,' Int. J. Radiat. Biol., 74, 755-764(1998) https://doi.org/10.1080/095530098141032
  6. R.L. Ullrich, M.D. Bowles, L.C. Satterfiled and CM. Davis, 'Strain dependent susceptibility background on mammary tumorigenesis in p53 deficient mice.' Cancer Res, 61, 6577-6582 (2001)
  7. G.E. Watson, S.A. Lorimore, S.M. Clutton, Kadhim MA and Wright EG, 'Genetic factors influencing alpha-particle induced chromosomal instability,' Int. J. Radiat. Biol., 71, 497-503(1997) https://doi.org/10.1080/095530097143824
  8. B. Ponnaiya, M.N. Cornforth and R.L. Ullrich, 'Radiation-induced chromosomal instability in BALB/c and C57BL/6 mice: the difference is as clear as black and white,' Radiat. Res., 147, 121-125(1997) https://doi.org/10.2307/3579411
  9. Y. Saito, Y. Ochiai, Y. Kodama, Y. Tamura, T. Togashi, H. Kosugi-Okano, T. Miyazawa, Y. Wakabayashi, K. Hatakeyama, S. Wakana, O. Niwa and R. Kominami, 'Genetic loci controlling susceptibility to gamma-ray induced thymic lymphoma,' Oncogene, 20, 5243-5247(2001) https://doi.org/10.1038/sj.onc.1204675
  10. E.A. Komarova, R.V. Kondratov, K. Wang, K. Christov, T.V. Golovkina, R. J. Goldblu and A.V. Gudkov, 'Dual effect of p53 on radiation sensitivity in vivo: p53 promotes hematopioetic injury, but protects from gastro-intestinal syndrome in mice,' Oncogene, 23, 3265-3271(2004) https://doi.org/10.1038/sj.onc.1207494
  11. S.M. Candeias, SJ. Mancini, C. Touvrey, E. Norel, E. Jouvin-Marche and P.N. Marche, 'p53-dependent and p53-independent pathways for radiation immature thymocyte differentiation.' Oncogene, 23, 1922-1929 (2004) https://doi.org/10.1038/sj.onc.1207320
  12. N. Mori, J. Yamate, S. Umesako, D.P. Hong, M. Okumoto and R. Nakao, 'Preferential induction of mammary tumors in p53 hemizygous mice by fractionated irradiation of a sub-lethal dose of X-rays,' J Radiat Res., 44, 249-254(2003) https://doi.org/10.1269/jrr.44.249
  13. H. Szymanska, M. Sitarz, E. Krysiak, J. Piskorowska, A. Czarnomska, H. Skurzak, A.A. Hark, D. de Jong and P. Demant, 'Genetics of susceptibility to radiation-induced lymphomas, leukemias and lung tumors studied in recombinant congenic strains,' Int. J. Cancer, 83, 674-678(1999) https://doi.org/10.1002/(SICI)1097-0215(19991126)83:5<674::AID-IJC18>3.0.CO;2-M
  14. C.W. van der Houven van Oordt, R. Smits, T.G. Schouten, J.J. Houwing-Duistermaat, S.L. A.A. Williamson, A. Luz, P. Meera Khan, A.J. van der Eb, and R. Fodde, 'The genetic background modifies the spontaneous and X-ray induced tumor spectrum in the Apc1638N mouse model,' Genes Chromosomes Cancer, 24,191-198(1999) https://doi.org/10.1002/(SICI)1098-2264(199903)24:3<191::AID-GCC3>3.0.CO;2-L
  15. C. Kuperwasser, G.D. Hurlbut, F.S. Kittrell, E.S. Dickinson, D. Laucirica, S.P. Naber, and D.J. Jerry, 'Development of spontaneous mammary tumors in BALC/c p53 heterozygous mice. A model for Li-Fraumeni syndrome,' Am. J. Pathol., 157, 2151-2159 (2000) https://doi.org/10.1016/S0002-9440(10)64853-5
  16. M.G. Backlund, S.L. Trasti, D.C. Backhand, V.L. Cressman and V. Godfrey, 'Impact of ionizing radiation and genetic background on mammary tumorigenesis in p53-deficient mice.' Cancer Res., 61, 6577-6582(2001)
  17. M.A. Kadhim, S.A. Lorimore, M.D. Hepburn, D.T. Goodhead, V.J. Buckle and E.G. Wright, 'Alpha-particle induced chromosomal instability in human bone marrow cells.' Lancet, 344, 5243-5247(1994)
  18. N.G. Burnet, R. Wurm, J. Nyman and J.H. Peacock, 'Normal tissue radiosenstivity- how important is it?' Clin. Oncol, 8, 25-34(1996) https://doi.org/10.1016/S0936-6555(05)80035-4
  19. C.E. Mothersill, KJ. O'Malley, D.M. Murphy, C.B. Seymour, S.A. Lorimore and E.G. Wright, 'Identification and characterization of three subtypes of radiation response in normal human epithelial cultures exposed to ionizing radiation,' Carcinogenesis, 20, 2273-2278(1999) https://doi.org/10.1093/carcin/20.12.2273
  20. C.S. Potten, 'Extreme sensitivity of some intestinal crypt cells to X and gamma irradiation. Nature, 269, 518-521(1977) https://doi.org/10.1038/269518a0
  21. R. Brent, 'Genomic biology,' Cell, 1, 169-183 (2000)
  22. D.J. Lockhart and E. A. Winzeler, 'Genomics, gene expression and DNA arrays,' Nature, 405, 827-836(2000) https://doi.org/10.1038/35015701
  23. J.A. Rininger, V.A. Dipippo and B.E. Rothberg, 'Differential gene expression technologies for identifying surrogate markers of drug efficacy and toxicity,' Drug Discovery Today, 5, 560-568(2000) https://doi.org/10.1016/S1359-6446(00)01597-X
  24. S.A. Amundson, M. Bittner, P. Meltzer, J. Trent and A. Fornace Jr., 'Induction of gene expression as a monitor of exposure to ionizing radiation,' Radiat. Res., 156, 657-661(2001) https://doi.org/10.1667/0033-7587(2001)156[0657:IOGEAA]2.0.CO;2
  25. Y.M. Chung, B.G. Kim, C.S. Park, S.J. Huh, J. Kim, J.K. Park, S.M. Cho, B.S. Kim, J.S. Kim, Y.D. Yoo and D.S. Bae, 'Increased expression of ICAM-3 is associated with radiation resistance in cervical cancer.' Int. J. Cancer, in press,(2005)
  26. J. Lamartine, N. Franco, P. Le Minter, P. Soularue, O. Alibert, J.J. Leplat, X. Gidrol, G. Waksman and M.T. Martin, 'Activation of an energy providing response in human keratinocytes after gamma irradiation,' J. Cell Biochem., 95, 620-631(2005) https://doi.org/10.1002/jcb.20394
  27. CM. Kang, K.P. Park, J.E. Song, E.I. Jeoung, C.K. Cho, T.H. Kim, S. Bae, S.J. Lee and Y.S. Lee, 'Possible biomarkers for ionizing radiation exposure in human peripheral blood lymphocytes,' Radiat. Res., 159, 312-319 (2003) https://doi.org/10.1667/0033-7587(2003)159[0312:PBFIRE]2.0.CO;2
  28. P. Fei, Bernhard E.J. and W.S. El-Deiry, 'Tissue-specific induction of p53 targets in Vivo,' Cancer Res., 62, 7316-7327(2002)
  29. D.S. Gridley, R.B. Bonnet, D.A. Bush, C. Franke, G.A. Cheek, J.D. Slater and J.M. Slater, 'Time course of serum cytokines in patients receiving proteon or combined photon/proton earn radiation for respectablebut medically inoperable non-small cell lung cancer,' Int. J. Radiat. Oncol. Biol. Phys., 60, 759-766(2004) https://doi.org/10.1016/j.ijrobp.2004.04.022
  30. S. Schultze-Mosgau, B. Lehner, F. Rodel, F. Wehrhan, K. Amann, J. Kopp, M. Thorwarth, E. Nkenke and G. Grabenbauer, 'Expression of bone morphogenic protein 2/4, transforming growth factor-beta 1, and bone matrix protein expression in healing area between vascular tibia grafts and irradiated bone-experimental model of osteonecrosis,' Int. J. Radiat. Oncol. Biol. Phys., 61, 1189-1196(2004)