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Radiation Induced DNA-Damage/Repair and Associated Signaling Pathways

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Targeted Radionuclide Tumor Therapy

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Summary

Radiation-induced DNA damage and related repair mechanisms are described in this chapter. The emerging connection with growth factor induced signal transduction is described, with important implications for radiotherapy. The prospect of developing targeting agents, which selectively deliver radioactivity to the tumor and at the same time radiosensitize the tumor cells is discussed in some detail.

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Abbreviations

ATM:

Ataxia telangiectasia mutated

DAG:

1,2-diacylglycerol

DSB:

DNA double-strand breaks

DNA-PK:

DNA dependent protein kinase

EGF:

Epidermal growth factor

EGFR:

EGF receptor

Erk:

Extracellular regulated kinase

HER:

Human epidermal growth factor receptor

HR:

Homologous recombination

LET:

Linear energy transfer

PI:

Phosphatidylinositol

PLC:

Phospholipase C

PTEN:

Phosphatase and tensin homolog deleted on chromosome 10

References

  1. Niida, H. and Nakanishi, M. (2006) DNA damage checkpoints in mammals. Mutagenesis, 21, 3-9.

    Article  PubMed  Google Scholar 

  2. Bakkenist, C.J. and Kastan, M.B. (2004) Initiating cellular stress responses. Cell, 118, 9-17.

    Article  PubMed  Google Scholar 

  3. Roos, W.P. and Kaina, B. (2006) DNA damage-induced cell death by apoptosis. Trends Mol Med, 12, 440-50.

    Article  PubMed  Google Scholar 

  4. Vispe, S. and Satoh, M.S. (2000) DNA repair patch-mediated double strand DNA break formation in human cells. J Biol Chem, 275, 27386-92.

    PubMed  Google Scholar 

  5. Stenerlöw, B., Karlsson, K.H., Cooper, B. and Rydberg, B. (2003) Measurement of prompt DNA double-strand breaks in mammalian cells without including heat-labile sites: results for cells deficient in nonhomologous end joining. Radiat Res, 159, 502-10.

    Article  PubMed  Google Scholar 

  6. Norbury, C.J. and Zhivotovsky, B. (2004) DNA damage-induced apoptosis. Oncogene, 23, 2797-808.

    Article  PubMed  Google Scholar 

  7. Petrini, J.H. and Stracker, T.H. (2003) The cellular response to DNA double-strand breaks: defining the sensors and mediators. Trends Cell Biol, 13, 458-62.

    Article  PubMed  Google Scholar 

  8. Yang, J., Yu, Y., Hamrick, H.E. and Duerksen-Hughes, P.J. (2003) ATM, ATR and DNA-PK: initiators of the cellular genotoxic stress responses. Carcinogenesis, 24, 1571-80.

    Article  PubMed  Google Scholar 

  9. Lee, J.H. and Paull, T.T. (2005) ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex. Science, 308, 551-4.

    Article  PubMed  Google Scholar 

  10. Rogakou, E.P., Pilch, D.R., Orr, A.H., Ivanova, V.S. and Bonner, W.M. (1998) DNA doublestranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem, 273, 5858-68.

    Article  PubMed  Google Scholar 

  11. Jazayeri, A., Falck, J., Lukas, C., Bartek, J., Smith, G.C., Lukas, J. and Jackson, S.P. (2006) ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks. Nat Cell Biol, 8, 37-45.

    Article  PubMed  Google Scholar 

  12. Bartek, J. and Lukas, J. (2003) Chk1 and Chk2 kinases in checkpoint control and cancer. Cancer Cell, 3, 421-9.

    Article  PubMed  Google Scholar 

  13. Zhou, B.B., Anderson, H.J. and Roberge, M. (2003) Targeting DNA checkpoint kinases in cancer therapy. Cancer Biol Ther, 2, S16-22.

    PubMed  Google Scholar 

  14. Viniegra, J.G., Martinez, N., Modirassari, P., Losa, J.H., Parada Cobo, C., Lobo, V.J., Luquero, C.I., Alvarez-Vallina, L., Ramon y Cajal, S., Rojas, J.M. and Sanchez-Prieto, R. (2005) Full activation of PKB/Akt in response to insulin or ionizing radiation is mediated through ATM. J Biol Chem, 280, 4029-36.

    Article  PubMed  Google Scholar 

  15. Panta, G.R., Kaur, S., Cavin, L.G., Cortes, M.L., Mercurio, F., Lothstein, L., Sweatman, T.W., Israel, M. and Arsura, M. (2004) ATM and the catalytic subunit of DNA-dependent protein kinase activate NF-kappaB through a common MEK/extracellular signal-regulated kinase/p90(rsk) signaling pathway in response to distinct forms of DNA damage. Mol Cell Biol, 24, 1823-35.

    Article  PubMed  Google Scholar 

  16. Dragoi, A.M., Fu, X., Ivanov, S., Zhang, P., Sheng, L., Wu, D., Li, G.C. and Chu, W.M. (2005) DNA-PKcs, but not TLR9, is required for activation of Akt by CpG-DNA. EMBO J, 24, 779-89.

    Article  PubMed  Google Scholar 

  17. Feng, J., Park, J., Cron, P., Hess, D. and Hemmings, B.A. (2004) Identification of a PKB/Akt hydrophobic motif Ser-473 kinase as DNA-dependent protein kinase. J Biol Chem, 279, 41189-96.

    Article  PubMed  Google Scholar 

  18. Bartkova, J., Horejsi, Z., Koed, K., Kramer, A., Tort, F., Zieger, K., Guldberg, P., Sehested, M., Nesland, J.M., Lukas, C., Orntoft, T., Lukas, J. and Bartek, J. (2005) DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature, 434, 864-70.

    Article  PubMed  Google Scholar 

  19. van Gent, D.C., Hoeijmakers, J.H. and Kanaar, R. (2001) Chromosomal stability and the DNA double-stranded break connection. Nat Rev Genet, 2, 196-206.

    Article  PubMed  Google Scholar 

  20. DiBiase, S.J., Zeng, Z.C., Chen, R., Hyslop, T., Curran, W.J., Jr. and Iliakis, G. (2000) DNAdependent protein kinase stimulates an independently active, nonhomologous, end-joining apparatus. Cancer Res, 60, 1245-53.

    PubMed  Google Scholar 

  21. Radulescu, I., Elmroth, K. and Stenerlöw, B. (2004) Chromatin organization contributes to non-randomly distributed double-strand breaks after exposure to high-LET radiation. Radiat Res, 161, 1-8.

    Article  PubMed  Google Scholar 

  22. Stenerlöw, B., Höglund, E., Carlsson, J. and Blomquist, E. (2000) Rejoining of DNA fragments produced by radiations of different linear energy transfer. Int J Radiat Biol, 76, 549-57.

    Article  PubMed  Google Scholar 

  23. Karlsson, K.H. and Stenerlöw, B. (2004) Focus formation of DNA repair proteins in normal and repair-deficient cells irradiated with high-LET ions. Radiat Res, 161, 517-27.

    Article  PubMed  Google Scholar 

  24. Foster, F.M., Traer, C.J., Abraham, S.M. and Fry, M.J. (2003) The phosphoinositide (PI) 3-kinase family. J Cell Sci, 116, 3037-40.

    Article  PubMed  Google Scholar 

  25. Coffer, P.J., Jin, J. and Woodgett, J.R. (1998) Protein kinase B (c-Akt): a multifunctional mediator of phosphatidylinositol 3-kinase activation. Biochem J, 335 (Pt 1), 1-13.

    PubMed  Google Scholar 

  26. Andjelkovic, M., Alessi, D.R., Meier, R., Fernandez, A., Lamb, N.J., Frech, M., Cron, P., Cohen, P., Lucocq, J.M. and Hemmings, B.A. (1997) Role of translocation in the activation and function of protein kinase B. J Biol Chem, 272, 31515-24.

    Article  PubMed  Google Scholar 

  27. Meier, R., Alessi, D.R., Cron, P., Andjelkovic, M. and Hemmings, B.A. (1997) Mitogenic activation, phosphorylation, and nuclear translocation of protein kinase Bbeta. J Biol Chem, 272, 30491-7.

    Article  PubMed  Google Scholar 

  28. Zha, J., Harada, H., Yang, E., Jockel, J. and Korsmeyer, S.J. (1996) Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L). Cell, 87, 619-28.

    Article  PubMed  Google Scholar 

  29. Datta, S.R., Dudek, H., Tao, X., Masters, S., Fu, H., Gotoh, Y. and Greenberg, M.E. (1997) Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell, 91, 231-41.

    Article  PubMed  Google Scholar 

  30. Medema, R.H., Kops, G.J., Bos, J.L. and Burgering, B.M. (2000) AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1. Nature, 404, 782-7.

    Article  PubMed  Google Scholar 

  31. Liang, J., Zubovitz, J., Petrocelli, T., Kotchetkov, R., Connor, M.K., Han, K., Lee, J.H., Ciarallo, S., Catzavelos, C., Beniston, R., Franssen, E. and Slingerland, J.M. (2002) PKB/Akt phosphorylates p27, impairs nuclear import of p27 and opposes p27-mediated G1 arrest. Nat Med, 8, 1153-60.

    Article  PubMed  Google Scholar 

  32. Shin, I., Yakes, F.M., Rojo, F., Shin, N.Y., Bakin, A.V., Baselga, J. and Arteaga, C.L. (2002) PKB/Akt mediates cell-cycle progression by phosphorylation of p27(Kip1) at threonine 157 and modulation of its cellular localization. Nat Med, 8, 1145-52.

    Article  PubMed  Google Scholar 

  33. Viglietto, G., Motti, M.L., Bruni, P., Melillo, R.M., D’Alessio, A., Califano, D., Vinci, F., Chiappetta, G., Tsichlis, P., Bellacosa, A., Fusco, A. and Santoro, M. (2002) Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Aktmediated phosphorylation in breast cancer. Nat Med, 8, 1136-44.

    Article  PubMed  Google Scholar 

  34. Chu, E.C. and Tarnawski, A.S. (2004) PTEN regulatory functions in tumor suppression and cell biology. Med Sci Monit, 10, RA235-41.

    PubMed  Google Scholar 

  35. Kim, I.A., Bae, S.S., Fernandes, A., Wu, J., Muschel, R.J., McKenna, W.G., Birnbaum, M.J. and Bernhard, E.J. (2005) Selective inhibition of Ras, phosphoinositide 3 kinase, and Akt isoforms increases the radiosensitivity of human carcinoma cell lines. Cancer Res, 65, 7902-10.

    PubMed  Google Scholar 

  36. Tanno, S., Yanagawa, N., Habiro, A., Koizumi, K., Nakano, Y., Osanai, M., Mizukami, Y., Okumura, T., Testa, J.R. and Kohgo, Y. (2004) Serine/threonine kinase AKT is frequently activated in human bile duct cancer and is associated with increased radioresistance. Cancer Res, 64, 3486-90.

    Article  PubMed  Google Scholar 

  37. Lee, C.M., Fuhrman, C.B., Planelles, V., Peltier, M.R., Gaffney, D.K., Soisson, A.P., Dodson, M.K., Tolley, H.D., Green, C.L. and Zempolich, K.A. (2006) Phosphatidylinositol 3-kinase inhibition by LY294002 radiosensitizes human cervical cancer cell lines. Clin Cancer Res, 12, 250-6.

    Article  PubMed  Google Scholar 

  38. Tan, J. and Hallahan, D.E. (2003) Growth factor-independent activation of protein kinase B contributes to the inherent resistance of vascular endothelium to radiation-induced apoptotic response. Cancer Res, 63, 7663-7.

    PubMed  Google Scholar 

  39. Edwards, E., Geng, L., Tan, J., Onishko, H., Donnelly, E. and Hallahan, D.E. (2002) Phosphatidylinositol 3-kinase/Akt signaling in the response of vascular endothelium to ionizing radiation. Cancer Res, 62, 4671-7.

    PubMed  Google Scholar 

  40. Lewis, T.S., Shapiro, P.S. and Ahn, N.G. (1998) Signal transduction through MAP kinase cascades. Adv Cancer Res, 74, 49-139.

    Article  PubMed  Google Scholar 

  41. Thompson, N. and Lyons, J. (2005) Recent progress in targeting the Raf/MEK/ERK pathway with inhibitors in cancer drug discovery. Curr Opin Pharmacol, 5, 350-6.

    Article  PubMed  Google Scholar 

  42. Chen, R.H., Sarnecki, C. and Blenis, J. (1992) Nuclear localization and regulation of erk- and rsk-encoded protein kinases. Mol Cell Biol, 12, 915-27.

    PubMed  Google Scholar 

  43. Rodriguez-Viciana, P., Warne, P.H., Dhand, R., Vanhaesebroeck, B., Gout, I., Fry, M.J., Waterfield, M.D. and Downward, J. (1994) Phosphatidylinositol-3-OH kinase as a direct target of Ras. Nature, 370, 527-32.

    Article  PubMed  Google Scholar 

  44. Kim, I.A., Fernandes, A.T., Gupta, A.K., McKenna, W.G. and Bernhard, E.J. (2004) The influence of Ras pathway signaling on tumor radiosensitivity. Cancer Metastasis Rev, 23, 227-36.

    Article  PubMed  Google Scholar 

  45. Wilde, J.I. and Watson, S.P. (2001) Regulation of phospholipase C gamma isoforms in haematopoietic cells: why one, not the other? Cell Signal, 13, 691-701.

    Article  PubMed  Google Scholar 

  46. Berridge, M.J., Lipp, P. and Bootman, M.D. (2000) The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol, 1, 11-21.

    Article  PubMed  Google Scholar 

  47. Liu, W.S. and Heckman, C.A. (1998) The sevenfold way of PKC regulation. Cell Signal, 10, 529-42.

    Article  PubMed  Google Scholar 

  48. Plo, I., Lautier, D., Casteran, N., Dubreuil, P., Arock, M. and Laurent, G. (2001) Kit signaling and negative regulation of daunorubicin-induced apoptosis: role of phospholipase Cgamma. Oncogene, 20, 6752-63.

    Article  PubMed  Google Scholar 

  49. Maddens, S., Charruyer, A., Plo, I., Dubreuil, P., Berger, S., Salles, B., Laurent, G. and Jaffrezou, J.P. (2002) Kit signaling inhibits the sphingomyelin-ceramide pathway through PLC gamma 1: implication in stem cell factor radioprotective effect. Blood, 100, 1294-301.

    PubMed  Google Scholar 

  50. Todd, D.G., Mikkelsen, R.B., Rorrer, W.K., Valerie, K. and Schmidt-Ullrich, R.K. (1999) Ionizing radiation stimulates existing signal transduction pathways involving the activation of epidermal growth factor receptor and ERBB-3, and changes of intracellular calcium in A431 human squamous carcinoma cells. J Recept Signal Transduct Res, 19, 885-908.

    Article  PubMed  Google Scholar 

  51. Karin, M. (1999) How NF-kappaB is activated: the role of the IkappaB kinase (IKK) complex. Oncogene, 18, 6867-74.

    Article  PubMed  Google Scholar 

  52. Barkett, M. and Gilmore, T.D. (1999) Control of apoptosis by Rel/NF-kappaB transcription factors. Oncogene, 18, 6910-24.

    Article  PubMed  Google Scholar 

  53. Kato, T., Duffey, D.C., Ondrey, F.G., Dong, G., Chen, Z., Cook, J.A., Mitchell, J.B. and Van Waes, C. (2000) Cisplatin and radiation sensitivity in human head and neck squamous carcinomas are independently modulated by glutathione and transcription factor NF-kappaB. Head Neck, 22, 748-59.

    Article  PubMed  Google Scholar 

  54. Miyakoshi, J. and Yagi, K. (2000) Inhibition of I kappaB-alpha phosphorylation at serine and tyrosine acts independently on sensitization to DNA damaging agents in human glioma cells. Br J Cancer, 82, 28-33.

    Article  PubMed  Google Scholar 

  55. Dery, M.A., Michaud, M.D. and Richard, D.E. (2005) Hypoxia-inducible factor 1: regulation by hypoxic and non-hypoxic activators. Int J Biochem Cell Biol, 37, 535-40.

    Article  PubMed  Google Scholar 

  56. Maxwell, P.H. (2005) The HIF pathway in cancer. Semin Cell Dev Biol, 16, 523-30.

    Article  PubMed  Google Scholar 

  57. Zundel, W., Schindler, C., Haas-Kogan, D., Koong, A., Kaper, F., Chen, E., Gottschalk, A.R., Ryan, H.E., Johnson, R.S., Jefferson, A.B., Stokoe, D. and Giaccia, A.J. (2000) Loss of PTEN facilitates HIF-1-mediated gene expression. Genes Dev, 14, 391-6.

    PubMed  Google Scholar 

  58. Fukuda, R., Hirota, K., Fan, F., Jung, Y.D., Ellis, L.M. and Semenza, G.L. (2002) Insulin-like growth factor 1 induces hypoxia-inducible factor 1-mediated vascular endothelial growth factor expression, which is dependent on MAP kinase and phosphatidylinositol 3-kinase signaling in colon cancer cells. J Biol Chem, 277, 38205-11.

    Article  PubMed  Google Scholar 

  59. Jiang, B.H., Jiang, G., Zheng, J.Z., Lu, Z., Hunter, T. and Vogt, P.K. (2001) Phosphatidylinositol 3-kinase signaling controls levels of hypoxia-inducible factor 1. Cell Growth Differ, 12, 363-9.

    PubMed  Google Scholar 

  60. Laughner, E., Taghavi, P., Chiles, K., Mahon, P.C. and Semenza, G.L. (2001) HER2 (neu) signaling increases the rate of hypoxia-inducible factor 1alpha (HIF-1alpha) synthesis: novel mechanism for HIF-1-mediated vascular endothelial growth factor expression. Mol Cell Biol, 21, 3995-4004.

    Article  PubMed  Google Scholar 

  61. Giatromanolaki, A., Koukourakis, M.I., Simopoulos, C., Polychronidis, A., Gatter, K.C., Harris, A.L. and Sivridis, E. (2004) c-erbB-2 related aggressiveness in breast cancer is hypoxia inducible factor-1alpha dependent. Clin Cancer Res, 10, 7972-7.

    Article  PubMed  Google Scholar 

  62. Shi, M., Guo, X.T., Shu, M.G., Chen, F.L. and Li, L.W. (2007) Cell-permeable hypoxia-inducible factor-1 (HIF-1) antagonists function as tumor radiosensitizers. Med Hypotheses, 69, 33-35.

    Article  PubMed  Google Scholar 

  63. Golding, S.E., Rosenberg, E., Neill, S., Dent, P., Povirk, L.F. and Valerie, K. (2007) Extracellular signal-related kinase positively regulates ataxia telangiectasia mutated, homolo- gous recombination repair, and the DNA damage response. Cancer Res, 67, 1046-53.

    Article  PubMed  Google Scholar 

  64. Irarrazabal, C.E., Burg, M.B., Ward, S.G. and Ferraris, J.D. (2006) Phosphatidylinositol 3-kinase mediates activation of ATM by high NaCl and by ionizing radiation: role in osmoprotective transcriptional regulation. Proc Natl Acad Sci USA, 103, 8882-7.

    Article  PubMed  Google Scholar 

  65. Dittmann, K., Mayer, C., Fehrenbacher, B., Schaller, M., Raju, U., Milas, L., Chen, D.J., Kehlbach, R. and Rodemann, H.P. (2005) Radiation-induced epidermal growth factor receptor nuclear import is linked to activation of DNA-dependent protein kinase. J Biol Chem, 280, 31182-9.

    Article  PubMed  Google Scholar 

  66. Dittmann, K., Mayer, C. and Rodemann, H.P. (2005) Inhibition of radiation-induced EGFR nuclear import by C225 (Cetuximab) suppresses DNA-PK activity. Radiother Oncol, 76, 157-61.

    Article  PubMed  Google Scholar 

  67. Bandyopadhyay, D., Mandal, M., Adam, L., Mendelsohn, J. and Kumar, R. (1998) Physical interaction between epidermal growth factor receptor and DNA-dependent protein kinase in mammalian cells. J Biol Chem, 273, 1568-73.

    Article  PubMed  Google Scholar 

  68. Friedmann, B., Caplin, M., Hartley, J.A. and Hochhauser, D. (2004) Modulation of DNA repair in vitro after treatment with chemotherapeutic agents by the epidermal growth factor receptor inhibitor gefitinib (ZD1839). Clin Cancer Res, 10, 6476-86.

    Article  PubMed  Google Scholar 

  69. Huang, S.M. and Harari, P.M. (2000) Modulation of radiation response after epidermal growth factor receptor blockade in squamous cell carcinomas: inhibition of damage repair, cell cycle kinetics, and tumor angiogenesis. Clin Cancer Res, 6, 2166-74.

    PubMed  Google Scholar 

  70. Lucero, H., Gae, D. and Taccioli, G.E. (2003) Novel localization of the DNA-PK complex in lipid rafts: a putative role in the signal transduction pathway of the ionizing radiation response. J Biol Chem, 278, 22136-43.

    Article  PubMed  Google Scholar 

  71. Knebel, A., Rahmsdorf, H.J., Ullrich, A. and Herrlich, P. (1996) Dephosphorylation of receptor tyrosine kinases as target of regulation by radiation, oxidants or alkylating agents. EMBO J, 15, 5314-25.

    PubMed  Google Scholar 

  72. Ostman, A. and Bohmer, F.D. (2001) Regulation of receptor tyrosine kinase signaling by protein tyrosine phosphatases. Trends Cell Biol, 11, 258-66.

    Article  PubMed  Google Scholar 

  73. Ma, B.B., Bristow, R.G., Kim, J. and Siu, L.L. (2003) Combined-modality treatment of solid tumors using radiotherapy and molecular targeted agents. J Clin Oncol, 21, 2760-76.

    Article  PubMed  Google Scholar 

  74. Connell, P.P., Kron, S.J. and Weichselbaum, R.R. (2004) Relevance and irrelevance of DNA damage response to radiotherapy. DNA Repair (Amst), 3, 1245-51.

    Article  Google Scholar 

  75. Pawlik, T.M. and Keyomarsi, K. (2004) Role of cell cycle in mediating sensitivity to radiotherapy. Int J Radiat Oncol Biol Phys, 59, 928-42.

    Article  PubMed  Google Scholar 

  76. Willers, H., Dahm-Daphi, J. and Powell, S.N. (2004) Repair of radiation damage to DNA. Br J Cancer, 90, 1297-301.

    Article  PubMed  Google Scholar 

  77. Hennessy, B.T., Smith, D.L., Ram, P.T., Lu, Y. and Mills, G.B. (2005) Exploiting the PI3K/ AKT pathway for cancer drug discovery. Nat Rev Drug Discov, 4, 988-1004.

    Article  PubMed  Google Scholar 

  78. Shintani, S., Li, C., Mihara, M., Terakado, N., Yano, J., Nakashiro, K. and Hamakawa, H. (2003) Enhancement of tumor radioresponse by combined treatment with gefitinib (Iressa, ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor, is accompanied by inhibition of DNA damage repair and cell growth in oral cancer. Int J Cancer, 107, 1030-7.

    Article  PubMed  Google Scholar 

  79. Sartor, C.I. (2004) Mechanisms of disease: Radiosensitization by epidermal growth factor receptor inhibitors. Nat Clin Pract Oncol, 1, 80-7.

    Article  PubMed  Google Scholar 

  80. Lennartsson, J., Carlsson, J. and Stenerlöw, B. (2006) Targeting the epidermal growth factor receptor family in radionuclide therapy of tumors-signal transduction and DNA repair. Lett Drug Des Discov, 3, 357-368.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Oncology, Radiology and Clinical Immunology, Rudbeck Laboratory, Uppsala University, SE-751 85, Uppsala, Sweden

    Bo Stenerlöw, Lina Ekerljung & Jörgen Carlsson

  2. Ludwig Institute for Cancer Research, Uppsala University, Box 595, SE-751 24, Uppsala, Sweden

    Johan Lennartsson

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  1. Bo Stenerlöw
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  2. Lina Ekerljung
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  3. Jörgen Carlsson
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  4. Johan Lennartsson
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Editors and Affiliations

  1. Department of Immunology, University of Umea, Umea, Sweden

    Torgny Stigbrand

  2. Rudbeck Laboratory, Uppsala University, Uppsala, Sweden

    Jörgen Carlsson

  3. Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, USA

    Gregory P. Adams

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Stenerlöw, B., Ekerljung, L., Carlsson, J., Lennartsson, J. (2008). Radiation Induced DNA-Damage/Repair and Associated Signaling Pathways. In: Stigbrand, T., Carlsson, J., Adams, G.P. (eds) Targeted Radionuclide Tumor Therapy. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-8696-0_13

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