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MeSH Review

Radiation Tolerance

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Disease relevance of Radiation Tolerance


Psychiatry related information on Radiation Tolerance


High impact information on Radiation Tolerance

  • DNA nonhomologous end-joining (NHEJ) is a predominant pathway of DNA double-strand break repair in mammalian cells, and defects in it cause radiosensitivity at the cellular and whole-organism levels [8].
  • Human T-B-severe combined immunodeficiency associated with increased cellular radiosensitivity (RS-SCID) is characterized by a defect in the V(D)J recombination leading to an early arrest of both B and T cell maturation [9].
  • Phosphorylation of this site appears to be functionally important because mutated nibrin (S343A) does not completely complement radiosensitivity in NBS cells [10].
  • The Rad50 hook is functional, because mutations in this motif confer radiation sensitivity in yeast and disrupt binding at the distant Mre11 nuclease interface [11].
  • This reciprocal relationship of radiosensitivity to anomalies and to embryonic or fetal lethality supports the notion that embryonic or fetal tissues have a p53-dependent "guardian" of the tissue that aborts cells bearing radiation-induced teratogenic DNA damage [12].

Chemical compound and disease context of Radiation Tolerance


Biological context of Radiation Tolerance


Anatomical context of Radiation Tolerance


Associations of Radiation Tolerance with chemical compounds


Gene context of Radiation Tolerance

  • Rif1 inhibition resulted in radiosensitivity and a defect in the intra-S-phase checkpoint [33].
  • The significant radiosensitivity of Artemis-deficient cells demonstrates the importance of this component of DSB repair to survival [34].
  • Mre11 deficiency also causes increased radiosensitivity and strongly reduced targeted integration frequencies [35].
  • However, yku70 mutations enhance the radiosensitivity of rad52 strains, which are deficient in homologous recombination [36].
  • These studies have also defined an element of the radiation sensitivity caused by loss of Rad17 function which is not associated with the radiation-induced G2 arrest defect seen in the rad17.d null mutant cells [37].

Analytical, diagnostic and therapeutic context of Radiation Tolerance

  • The presence of EGF in the cell culture either after irradiation (during the clonogenic assay period) or continuously before, during, and after irradiation enhanced the radiosensitivity of the cells and reduced their plating efficiency (PE) [20].
  • The findings demonstrate that HDGF may play an important role in radiosensitivity, and it could be a novel marker predicting effectiveness of radiotherapy in clinical cases [38].
  • Antisense ATM gene therapy: a strategy to increase the radiosensitivity of human tumors [39].
  • Dextran sulfate injection mobilized normal numbers of CFU-GM into the blood early after transplantation, and spontaneously circulating CFU-GM in a later phase did not differ from blood progenitors of normal animals with respect to radiation sensitivity and sedimentation velocity [40].
  • Although the growth of SCLC cells in a clonogenic assay may be of value in chemotherapy selection, the established cell lines provide a model for studying mechanisms of drug and radiation sensitivity; and drug metabolism [41].


  1. ATM regulates target switching to escalating doses of radiation in the intestines. Ch'ang, H.J., Maj, J.G., Paris, F., Xing, H.R., Zhang, J., Truman, J.P., Cardon-Cardo, C., Haimovitz-Friedman, A., Kolesnick, R., Fuks, Z. Nat. Med. (2005) [Pubmed]
  2. Targeted disruption of the catalytic subunit of the DNA-PK gene in mice confers severe combined immunodeficiency and radiosensitivity. Taccioli, G.E., Amatucci, A.G., Beamish, H.J., Gell, D., Xiang, X.H., Torres Arzayus, M.I., Priestley, A., Jackson, S.P., Marshak Rothstein, A., Jeggo, P.A., Herrera, V.L. Immunity (1998) [Pubmed]
  3. Male sterility and enhanced radiation sensitivity in TLS(-/-) mice. Kuroda, M., Sok, J., Webb, L., Baechtold, H., Urano, F., Yin, Y., Chung, P., de Rooij, D.G., Akhmedov, A., Ashley, T., Ron, D. EMBO J. (2000) [Pubmed]
  4. ATM: genome stability, neuronal development, and cancer cross paths. Shiloh, Y., Kastan, M.B. Adv. Cancer Res. (2001) [Pubmed]
  5. Chromosomal radiosensitivity during the G2 cell-cycle period of skin fibroblasts from individuals with familial cancer. Parshad, R., Sanford, K.K., Jones, G.M. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  6. Nijmegen breakage syndrome cells fail to induce the p53-mediated DNA damage response following exposure to ionizing radiation. Jongmans, W., Vuillaume, M., Chrzanowska, K., Smeets, D., Sperling, K., Hall, J. Mol. Cell. Biol. (1997) [Pubmed]
  7. Clinical and genetic features of ataxia-telangiectasia. Bundey, S. Int. J. Radiat. Biol. (1994) [Pubmed]
  8. XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA nonhomologous end-joining. Ahnesorg, P., Smith, P., Jackson, S.P. Cell (2006) [Pubmed]
  9. Artemis, a novel DNA double-strand break repair/V(D)J recombination protein, is mutated in human severe combined immune deficiency. Moshous, D., Callebaut, I., de Chasseval, R., Corneo, B., Cavazzana-Calvo, M., Le Deist, F., Tezcan, I., Sanal, O., Bertrand, Y., Philippe, N., Fischer, A., de Villartay, J.P. Cell (2001) [Pubmed]
  10. ATM-dependent phosphorylation of nibrin in response to radiation exposure. Gatei, M., Young, D., Cerosaletti, K.M., Desai-Mehta, A., Spring, K., Kozlov, S., Lavin, M.F., Gatti, R.A., Concannon, P., Khanna, K. Nat. Genet. (2000) [Pubmed]
  11. The Rad50 zinc-hook is a structure joining Mre11 complexes in DNA recombination and repair. Hopfner, K.P., Craig, L., Moncalian, G., Zinkel, R.A., Usui, T., Owen, B.A., Karcher, A., Henderson, B., Bodmer, J.L., McMurray, C.T., Carney, J.P., Petrini, J.H., Tainer, J.A. Nature (2002) [Pubmed]
  12. p53-dependent apoptosis suppresses radiation-induced teratogenesis. Norimura, T., Nomoto, S., Katsuki, M., Gondo, Y., Kondo, S. Nat. Med. (1996) [Pubmed]
  13. Flavopiridol, a cyclin-dependent kinase inhibitor, enhances radiosensitivity of ovarian carcinoma cells. Raju, U., Nakata, E., Mason, K.A., Ang, K.K., Milas, L. Cancer Res. (2003) [Pubmed]
  14. Sphingosine enhances apoptosis of radiation-resistant prostate cancer cells. Nava, V.E., Cuvillier, O., Edsall, L.C., Kimura, K., Milstien, S., Gelmann, E.P., Spiegel, S. Cancer Res. (2000) [Pubmed]
  15. The optimal combination of hyperthermia and carbogen breathing to increase tumor oxygenation and radiation response. Griffin, R.J., Okajima, K., Song, C.W. Int. J. Radiat. Oncol. Biol. Phys. (1998) [Pubmed]
  16. Role of gamma-glutamyltranspeptidase-mediated glutathione transport on the radiosensitivity of B16 melanoma variant cell lines. Prezioso, J.A., Shields, D., Wang, N., Rosenstein, M. Int. J. Radiat. Oncol. Biol. Phys. (1994) [Pubmed]
  17. Effect of hyperthermia and misonidazole on the radiosensitivity of a transplantable murine tumor: influence of factors modifying the fraction of hypoxic cells. Wondergem, J., Haveman, J., van der Schueren, E., van den Hoeven, H., Breur, K. Int. J. Radiat. Oncol. Biol. Phys. (1982) [Pubmed]
  18. ATM phosphorylation of Nijmegen breakage syndrome protein is required in a DNA damage response. Wu, X., Ranganathan, V., Weisman, D.S., Heine, W.F., Ciccone, D.N., O'Neill, T.B., Crick, K.E., Pierce, K.A., Lane, W.S., Rathbun, G., Livingston, D.M., Weaver, D.T. Nature (2000) [Pubmed]
  19. PARP is important for genomic stability but dispensable in apoptosis. Wang, Z.Q., Stingl, L., Morrison, C., Jantsch, M., Los, M., Schulze-Osthoff, K., Wagner, E.F. Genes Dev. (1997) [Pubmed]
  20. Enhancement of sensitivity of human squamous carcinoma cells to radiation by epidermal growth factor. Kwok, T.T., Sutherland, R.M. J. Natl. Cancer Inst. (1989) [Pubmed]
  21. Role for the fission yeast RecQ helicase in DNA repair in G2. Laursen, L.V., Ampatzidou, E., Andersen, A.H., Murray, J.M. Mol. Cell. Biol. (2003) [Pubmed]
  22. The farnesyltransferase inhibitor FTI-277 radiosensitizes H-ras-transformed rat embryo fibroblasts. Bernhard, E.J., Kao, G., Cox, A.D., Sebti, S.M., Hamilton, A.D., Muschel, R.J., McKenna, W.G. Cancer Res. (1996) [Pubmed]
  23. Correction of radiation sensitivity in ataxia telangiectasia cells by a truncated I kappa B-alpha. Jung, M., Zhang, Y., Lee, S., Dritschilo, A. Science (1995) [Pubmed]
  24. Microbial regulation of intestinal radiosensitivity. Crawford, P.A., Gordon, J.I. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  25. Loss of p21 increases sensitivity to ionizing radiation and delays the onset of lymphoma in atm-deficient mice. Wang, Y.A., Elson, A., Leder, P. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  26. Radiation sensitivity of resting and activated nonspecific cytotoxic cells of T lineage and NK lineage. Zarcone, D., Tilden, A.B., Lane, V.G., Grossi, C.E. Blood (1989) [Pubmed]
  27. Selective inhibition of Ras, phosphoinositide 3 kinase, and Akt isoforms increases the radiosensitivity of human carcinoma cell lines. Kim, I.A., Bae, S.S., Fernandes, A., Wu, J., Muschel, R.J., McKenna, W.G., Birnbaum, M.J., Bernhard, E.J. Cancer Res. (2005) [Pubmed]
  28. Genome-wide expression analysis of therapy-resistant tumors reveals SPARC as a novel target for cancer therapy. Tai, I.T., Dai, M., Owen, D.A., Chen, L.B. J. Clin. Invest. (2005) [Pubmed]
  29. Radiosensitizing nucleosides. McGinn, C.J., Shewach, D.S., Lawrence, T.S. J. Natl. Cancer Inst. (1996) [Pubmed]
  30. Metronidazole: effect on radiosensitivity of tumor and normal tissues in mice. Stone, H.B., Withers, H.R. J. Natl. Cancer Inst. (1975) [Pubmed]
  31. Glutathione deficiency and radiosensitivity in AIDS patients. Vallis, K.A. Lancet (1991) [Pubmed]
  32. Increase in pO2 and radiosensitivity of tumors by Fluosol-DA (20%) and carbogen. Song, C.W., Lee, I., Hasegawa, T., Rhee, J.G., Levitt, S.H. Cancer Res. (1987) [Pubmed]
  33. Human Rif1, ortholog of a yeast telomeric protein, is regulated by ATM and 53BP1 and functions in the S-phase checkpoint. Silverman, J., Takai, H., Buonomo, S.B., Eisenhaber, F., de Lange, T. Genes Dev. (2004) [Pubmed]
  34. A pathway of double-strand break rejoining dependent upon ATM, Artemis, and proteins locating to gamma-H2AX foci. Riballo, E., Kühne, M., Rief, N., Doherty, A., Smith, G.C., Recio, M.J., Reis, C., Dahm, K., Fricke, A., Krempler, A., Parker, A.R., Jackson, S.P., Gennery, A., Jeggo, P.A., Löbrich, M. Mol. Cell (2004) [Pubmed]
  35. Mre11 is essential for the maintenance of chromosomal DNA in vertebrate cells. Yamaguchi-Iwai, Y., Sonoda, E., Sasaki, M.S., Morrison, C., Haraguchi, T., Hiraoka, Y., Yamashita, Y.M., Yagi, T., Takata, M., Price, C., Kakazu, N., Takeda, S. EMBO J. (1999) [Pubmed]
  36. Saccharomyces cerevisiae Ku70 potentiates illegitimate DNA double-strand break repair and serves as a barrier to error-prone DNA repair pathways. Boulton, S.J., Jackson, S.P. EMBO J. (1996) [Pubmed]
  37. Fission yeast rad17: a homologue of budding yeast RAD24 that shares regions of sequence similarity with DNA polymerase accessory proteins. Griffiths, D.J., Barbet, N.C., McCready, S., Lehmann, A.R., Carr, A.M. EMBO J. (1995) [Pubmed]
  38. Hepatoma-derived growth factor is associated with reduced sensitivity to irradiation in esophageal cancer. Matsuyama, A., Inoue, H., Shibuta, K., Tanaka, Y., Barnard, G.F., Sugimachi, K., Mori, M. Cancer Res. (2001) [Pubmed]
  39. Antisense ATM gene therapy: a strategy to increase the radiosensitivity of human tumors. Guha, C., Guha, U., Tribius, S., Alfieri, A., Casper, D., Chakravarty, P., Mellado, W., Pandita, T.K., Vikram, B. Gene Ther. (2000) [Pubmed]
  40. Fetal liver transplantation in the dog. II. Repopulation of the granulocyte-macrophage progenitor cell compartment by fetal liver cells from DLA-identical siblings. Prümmer, O., Werner, C., Raghavachar, A., Nothdurft, W., Calvo, W., Steinbach, K.H., Fliedner, T.M. Transplantation (1985) [Pubmed]
  41. Biological heterogeneity of small cell lung cancer. Carney, D.N., Gazdar, A.F., Nau, M., Minna, J.D. Semin. Oncol. (1985) [Pubmed]
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