Skip to main content

Advertisement

Log in

Genetic and epigenetic features in radiation sensitivity

Part II: implications for clinical practice and radiation protection

  • Review Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Recent progress especially in the field of gene identification and expression has attracted greater attention to the genetic and epigenetic susceptibility to cancer, possibly enhanced by ionising radiation. This issue is especially important for radiation therapists since hypersensitive patients may suffer from adverse effects in normal tissues following standard radiation therapy, while normally sensitive patients could receive higher doses of radiation, offering a better likelihood of cure for malignant tumours. Although only a small percentage of individuals are “hypersensitive” to radiation effects, all medical specialists using ionising radiation should be aware of the aforementioned progress in medical knowledge. The present paper, the second of two parts, reviews human disorders known or strongly suspected to be associated with hypersensitivity to ionising radiation. The main tests capable of detecting such pathologies in advance are analysed, and ethical issues regarding genetic testing are considered. The implications for radiation protection of possible hypersensitivity to radiation in a part of the population are discussed, and some guidelines for nuclear medicine professionals are proposed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Schmidt-Ullrich RK, Dent P, Grant S, Mikkelsen RB, Valerie K. Signal transduction and cellular radiation responses. Radiat Res 2000;153:245–47.

    Google Scholar 

  2. Dent P, Yacoub A, Contessa J, Caron R, Amorino G, Valerie K, et al. Stress and radiation-induced activation of multiple intracellular signalling pathways. Radiat Res 2003;159:283–300.

    Google Scholar 

  3. Twardella D, Chang-Claude J. Studies on radiosensitivity from an epidemiological point of view—overview of methods and results. Radiother Oncol 2002;62:249–60.

    Article  Google Scholar 

  4. Turreson I, Nyman J, Holmberg E, Odén A. Prognostic factors for acute and late skin reactions in radiotherapy patients. Int J Radiat Oncol Biol Phys 1996;36:1065–75.

    Google Scholar 

  5. Bourguignon MH, Gisone PA, Perez MR, Michelin S, Dubner D, Di Giorgio M, et al. Genetic and epigenetic features in radiation sensitivity. Part I: cell signalling in radiation response. Eur J Nucl Med Mol Imaging 2005;32 (in press).

  6. Lehmann AR. DNA repair-deficient diseases, xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy. Biochimie 2003;85:1101–11.

    Google Scholar 

  7. Cordonnier AM, Fuchs RP. Replication of damaged DNA: molecular defect in xeroderma pigmentosum variant cells. Mutat Res 1999;435:111–19.

    Google Scholar 

  8. Kannouche P, Stary A. Xeroderma pigmentosum variant and error prone DNA polymerases. Biochimie 2003;85:1123–32.

    Google Scholar 

  9. Limoli CL, Giedzinski E, Morgan WF, Cleaver JE. Polymerase η deficiency in the xeroderma pigmentosum variant uncovers an overlap between the S phase checkpoint and double-strand break repair. Proc Natl Acad Sci U S A 2000;97:7939–46.

    Google Scholar 

  10. Gatti RA, Berkel I, Boder E, Braedt G, Charmley P, Concannon P, et al. Localization of an ataxia-telangiectasia gene to chromosome 11q22–23. Nature 1988;336:577–80.

    Article  Google Scholar 

  11. Swift M. Genetics and epidemiology of ataxia-telangiectasia. Kroc Found Ser 1985;19:133–46.

    Google Scholar 

  12. Taylor AMR. Chromosome instability syndromes. Best Pract Res Clin Haematol 2001;14:631–44.

    Google Scholar 

  13. Pandita TK, Pathak S, Geard CR. Chromosome end associations, telomeres and telomerase activity in ataxia telangiectasia cells. Cytogenet Cell Genet 1995;71:86–93.

    Google Scholar 

  14. Wong KK, Maser RS, Bachoo RM, Menon J, Carrasco DR, Gu Y, et al. Telomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing. Nature 2003;42:643–8.

    Google Scholar 

  15. Hecht F, Hecht BK. Cancer in ataxia-telangiectasia patients. Cancer Genet Cytogenet 1990;46:9–19.

    Google Scholar 

  16. Weissberg JB, Huang DD, Swift M. Radiosensitivity of normal tissues in ataxia-telangiectasia heterozygotes. Int J Radiat Oncol Biol Phys 1998; 42:1133–6.

    Google Scholar 

  17. Angele S, Romestaing P, Moullan N, Vuillaume M, Chapot B, Friesen M, et al. ATM haplotypes and cellular response to DNA damage: association with breast cancer risk and clinical radiosensitivity Cancer Res 2003;63:8717–25.

    Google Scholar 

  18. Petrini JH, Theunissen JW. Double strand break metabolism and cancer susceptibility: lessons from the Mre11 complex. Cell Cycle 2004;3:541–2.

    Google Scholar 

  19. Digweed M. Response to environmental carcinogens in DNA-repair-deficient disorders. Toxicology 2003;193:111–24.

    Google Scholar 

  20. Roselli F, Briot D, Pichierri P. The Fanconi anemia pathway and the DNA interstrand cross-link repair. Biochimie 2003;85:1175–84.

    Google Scholar 

  21. Roselli F, Briot D, Pichieri P. The Fanconi anemia pathway and the DNA interstrand cross-link repair. Biochimie 2003;85:1175–84.

    Google Scholar 

  22. Howlett NG, Taniguchi T, Olson S, Cox B, Waisfisz Q, De Die-Smulders C, et al. Biallelic inactivation of BRCA2 in Fanconi anemia. Science 2002;297:606–9.

    Google Scholar 

  23. Duckworth-Rysiecki G, Taylor AM. Effects of ionizing radiation on cells from Fanconi’s anemia patients. Cancer Res 1985;45:416–20.

    Google Scholar 

  24. Djuzenova CS, Rothfuss A, Oppitz U, Spelt G, Schindler D, Hoehn H, et al. Response to X-irradiation of Fanconi anemia homozygous and heterozygous cells assessed by the single-cell gel electrophoresis (comet) assay. Lab Invest 2001;81:185–92.

    Google Scholar 

  25. Nakanishi K, Taniguchi T, Ranganathan V, New HV, Moreau LA, Stotsky M, et al. Interaction of FANCD2 and NBS1 in the DNA damage response. Nat Cell Biol 2002;4:913–20.

    Article  CAS  PubMed  Google Scholar 

  26. Kaneko H, Kondo N. Clinical features of Bloom syndrome and function of the causative gene, BLM helicase. Expert Rev Mol Diag 2004;4:393–401.

    Google Scholar 

  27. Bhisitkul RB, Rizen M. Bloom syndrome: multiple retinopathies in a chromosome breakage disorder. Br J Ophthalmol 2004;88:354–7.

    Google Scholar 

  28. Harrigan JA, Bohr VA. Human diseases deficient in RecQ helicases. Biochimie 2003;85:1185–93.

    Google Scholar 

  29. Franchitto A, Pichierri P. Bloom’s syndrome protein is required for correct relocalization of RAD50/MRE11/NBS1 complex after replication fork arrest. J Cell Biol 2002;157:19–30.

    Article  CAS  PubMed  Google Scholar 

  30. Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J. BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures. Genes Dev 2000;14:927–39.

    CAS  PubMed  Google Scholar 

  31. Gaymes TJ, North PS, Brady N, Hickson ID, Mufti GJ, Rassool FV. Increased error-prone non homologous DNA end-joining—a proposed mechanism of chromosomal instability in Bloom’s syndrome. Oncogene 2002;21:2525–33.

    Google Scholar 

  32. Wang LL, Levy ML, Lewis RA, Chintagumpala MM, Lev D, Rogers M, et al. Clinical manifestations in a cohort of 41 Rothmund-Thomson syndrome patients. Am J Med Genet 2001;102:11–7.

    Google Scholar 

  33. Wang LL, Gannavarapu A, Kozinetz CA, Levy ML, Lewis RA, Chintagumpala MM, et al. Association between osteosarcoma and deleterious mutations in the RECQL4 gene in Rothmund-Thomson syndrome. J Natl Cancer Inst 2003;95:669–74.

    Google Scholar 

  34. Stoll C, Labay F, Geisert J, Alembik Y. Wiedemann-Rautenstrauch syndrome. A case report and review of the literature. Genet Couns 1998;9:119–24.

    Google Scholar 

  35. Cao H, Hegele RA. LMNA is mutated in Hutchinson-Gilford progeria (MIM 176670) but not in Wiedemann-Rautenstrauch progeroid syndrome (MIM 264090). J Hum Genet 2003;48:271–4.

    Google Scholar 

  36. Bridger JM, Kill IR. Aging of Hutchinson-Gilford progeria syndrome fibroblasts is characterised by hyperproliferation and increased apoptosis. Exp Gerontol 2004;39:717–24.

    Google Scholar 

  37. Tuo J, Jaruga P, Rodriguez H, Bohr VA, Dizdaroglu M. Primary fibroblasts of Cockayne syndrome patients are defective in cellular repair of 8-hydroxyguanine and 8-hydroxyadenine and 8-hydroxyadenine resulting from oxidative stress. FASEB J 2003;17:668–74.

    Google Scholar 

  38. Yamamoto K, Imakiire A, Miyagawa N, Kasahara T. A report of two cases of Werner’s syndrome and review of the literature. J Orthop Surg (Hong Kong) 2003;11:224–33.

    Google Scholar 

  39. Machwe A, Xiao L. Orren DK TRF2 recruits the Werner syndrome (WRN) exonuclease for processing of telomeric DNA. Oncogene 2004;23:149–56.

    Article  CAS  PubMed  Google Scholar 

  40. Cheng WH, Von Kobbe C, Opresko PL, Arthur LM, Komatsu K, Seidman MM, et al. Linkage between Werner syndrome protein and the Mre11 Complex via Nbs1. J Biol Chem 2004;279:21169–76.

    Article  CAS  PubMed  Google Scholar 

  41. Less-Miller SP, Meek k. Repair of DNA double strand breaks by non-homologous end joining. Biochimie 2003;85:1161–73.

    Google Scholar 

  42. Dudasova Z, Chovanec M. Artemis, a novel guardian of the genome. Neoplasma 2003;50:311–8.

    Google Scholar 

  43. Moshous D, Pannetier C, Chasseval Rd R, Deist Fl F, Cavazzana-Calvo M, Romana S, et al. Partial T and B lymphocyte immunodeficiency and predisposition to lymphoma in patients with hypomorphic mutations in Artemis. J Clin Invest 2003;111:381–7.

    Google Scholar 

  44. O’Driscoll M, Cerosaletti KM, Girard PM, Dai Y, Stumm M, Kysela B, et al. DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency. Mol Cell 2001;8:1175–85.

    Google Scholar 

  45. O’Driscoll M, Ruiz-Perez VL, Woods CG, Jeggo PA, Goodship JA. A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome. Nat Genet 2003;33:497–501.

    Google Scholar 

  46. Comolli LR, Smirnov I, Xu L, Blackburn EH, James TL. A molecular switch underlies a human telomerase disease. Proc Natl Acad Sci U S A 2002;99:16998–7003.

    Google Scholar 

  47. Dokal I, Bungey J, Williamson P, Oscier D, Hows J, Luzzatto L. Dyskeratosis congenita fibroblasts are abnormal and have unbalanced chromosomal rearrangements. Blood 1992;80:3090–6.

    Google Scholar 

  48. Soder AI, Hoare SF, Muir S, Going JJ, Parkinson EK, Keith WN. Amplification, increased dosage and in situ expression of the telomerase RNA gene in human cancer. Oncogene 1997;14:1013–21.

    Google Scholar 

  49. Dokal I. Dyskeratosis congenita in all its forms. Br J Haematol 2000;110:768–79.

    Google Scholar 

  50. DeBauche DM, Pai GS, Stanley WS. Enhanced G2 chromatid radiosensitivity in dyskeratosis congenita fibroblasts. Am J Hum Genet 1990;46:350–7

    Google Scholar 

  51. Cengiz M, Celebioglu B, Ozyar E, Lale Atahan I. Unusual hypersensitivity to radiation therapy in a patient with dyskeratosis congenita syndrome. Oral Oncol 2004;40:758–9.

    Google Scholar 

  52. M’kacher R, Laithier V, Valent A, Delhommeau F, Violot D, Deutsch E, et al. Sensitivity to radiation and alkylating agent of peripheral lymphocytes and fibroblasts in a Hoyeraal-Hreidarsson syndrome patient. Pediat Hematol Oncol 2003;20:651–6.

    Google Scholar 

  53. Rebbeck TR. Biomarkers of inherited susceptibility and cancer. IARC Sci Publ 2004;157:91–103.

    Google Scholar 

  54. Barros RA, Ciammella SM, Schinoni MI. Hereditary familial non polypoid colorectal cancer. Acta Gastroenterol Latinoam 2001;31:23–6.

    Google Scholar 

  55. Mamon H, Dahlberg W, Little JB. Hemizygous fibroblast cell strains established from patients with BRCA1 or BRCA2 mutations demonstrate an increased rate of spontaneous mutations and increased radiosensitivity. Int J Radiat Oncol Biol Phys 2003;57:S346–7.

    Google Scholar 

  56. Fu YP, Yu JC, Cheng TC, Lou MA, Hsu GC, Wu CY, et al. Breast cancer risk associated with genotypic polymorphism of the nonhomologous end-joining genes: a multigenic study on cancer susceptibility. Cancer Res 2003;63:2440–6.

    CAS  PubMed  Google Scholar 

  57. Chang EH, Pirollo KF, Zou ZQ, Cheung HY, Lawler EL, Garner R, et al. Oncogenes in radioresistant, noncancerous skin fibroblasts from a cancer-prone family. Science 1987;237:1036–9.

    Google Scholar 

  58. Fletcher O, Easton D, Anderson K, Gilham C, Jay M, Peto J. Lifetime risks of common cancers among retinoblastoma survivors. J Natl Cancer Inst 2004;96:357–63.

    Google Scholar 

  59. Manfredi M, Vescovi P, Bonanini M, Porter S. Nevoid basal cell carcinoma syndrome: a review of the literature. Int J Oral Maxillofac Surg 2004; 33:117–24.

    CAS  PubMed  Google Scholar 

  60. Bisogno G, Sotti G, Nowicki Y, Ferrari A, Garaventa A, Zanetti I, et al. Soft tissue sarcoma as a second malignant neoplasm in the pediatric age group. Cancer 2004;100:1758–65.

    Google Scholar 

  61. Robbins JH, Otsuka F, Tarone RE, Polinsky RJ, Brumback RA, Nee LE. Parkinson’s disease and Alzheimer’s disease: hypersensitivity to X rays in cultured cell lines. Neurol Neurosurg Psychiatry 1985;48:916–23.

    Google Scholar 

  62. Chen P, Kidson C, Lavin M. Heterogeneity in Alzheimer’s disease: evidence from cellular radiosensitivity and complementation of this phenotype. Mutat Res 1991;256:21–7.

    Google Scholar 

  63. Real F, Krown SE, Nisce LZ, Oettgen HF. Unexpected toxicity from radiation therapy in two patients with Kaposi’s sarcoma receiving interferon. J Biol Resp Modif 1985;4:141–6.

    Google Scholar 

  64. Hughes-Davies L, Young T, Spittle M. Radiosensitivity in AIDS patients. Lancet 1991;337:1616.

    Google Scholar 

  65. Costleigh BJ, Miyamoto CT, Micaily B, Brady LW. Heightened sensitivity of the esophagus to radiation in a patient with AIDS. Am J Gastroenterol 1995;90:812–4.

    Google Scholar 

  66. Wu G, Fang YZ, Yang S, Lupton JR, Turner ND. Glutathione metabolism and its implications for health. J Nutr 2004;134:489–92.

    CAS  PubMed  Google Scholar 

  67. Vallis KA. Glutathione deficiency and radiosensitivity in AIDS patients. Lancet 1991;337:918–9.

    Google Scholar 

  68. Takeshita T, Ariizumi-Shibusawa C, Shimizu K, Hoshino H, Yamagata Z, Iijima S, et al. The effect of aging on cell-cycle kinetics and X-ray-induced chromosome aberrations in cultured lymphocytes from patients with Down syndrome. Mutat Res 1992;275:21–9.

    Google Scholar 

  69. Harris G, Cramp WA, Edwards JC, George AM, Sabovljev SA, Hart L, et al. Radiosensitivity of peripheral blood lymphocytes in autoimmune disease. Int J Radiat Biol Relat Stud Phys Chem Med 1985;47:689–99.

    Google Scholar 

  70. Morris MM, Powell SN. Irradiation in the setting of collagen vascular disease: acute and late complications. J Clin Oncol 1997;15:2728–35.

    Google Scholar 

  71. Cossu F, Rombi G, Aresu G, Pia G, Pascalis L. Radiosensitivity of lymphocyte subpopulations in subjects with systemic lupus erythematosus. An in vitro preliminary study. Minerva Med 1991;82:239–49.

    Google Scholar 

  72. West CML. Intrinsic radiosensibility as a predictor of patient response to radiotherapy. Br J Radiol 1995;68:827–37.

    Google Scholar 

  73. Fertil B, Malaise EP. Inherent cellular radiosensitivity as a basic concept for human tumor radiotherapy. Int J Radiat Oncol Biol Phys 1981;7:621–9.

    Google Scholar 

  74. Fertil B, Malaise EP. Intrinsic radiosensitivity of human cell lines is correlated with radioresponsiveness of human tumors: analysis of 101 published survival curves. Int J Radiat Oncol Biol Phys 1985;11:1699–707.

    Google Scholar 

  75. Malaise EP, Fertil B, Deschavanne PJ, Chavaudra N, Brock WA. Initial slope of radiation survival curves is characteristic of the origin of primary and established cultures of human tumor cells and fibroblasts. Radiat Res 1987;111:319–33.

    Google Scholar 

  76. Deacon J, Peckham MJ, Steel GG. The radioresponsiveness of human tumours and the initial slope of the cell survival curve. Radiother Oncol 1984;2:317–23.

    Google Scholar 

  77. Davidson SE, West CML, Hunter RD. Lack of association between in vitro clonogenic growth of human cervical carcinoma and tumor stage, differentiation, patient age, host cell infiltration or patient survival. Int J Cancer 1992;50:10–4.

    Google Scholar 

  78. Lawton PA, Hodgkiss RJ, Eyden BP, Joiner MC. Growth of fibroblast as a potential confounding factor in soft agar clonogenic assays for tumour cell radiosensitivity. Radiother Oncol 1994;12:218–25.

    Google Scholar 

  79. Geara FB, Peters LJ, Ang KK, Wike JL, Brock WA. Prospective comparison of in vitro normal cell radiosensitivity and normal tissue reactions in radiotherapy patients. Int J Radiat Oncol Biol Phys 1993;27:1173–9.

    Google Scholar 

  80. Loeffler JS, Harris JR, Dahlberg WK, Little JB. In vitro radiosensitivity of human diploid fibroblasts derived from women with unusually sensitive clinical responses to definitive radiation therapy for breast cancer. Radiat Res 1990;121:227–31.

    Google Scholar 

  81. Brock WA, Tucker SL, Geara FB, Turesson I, Wike J, Nyman J, et al. Fibroblasts radiosensitivity versus acute and late normal skin responses in breast cancer. Int J Radiat Oncol Biol Phys 1995;32:1371–9.

    Google Scholar 

  82. Johansen J, Bentzen SM, Overgaard J, Overgaard M. Relationship between the in vitro radiosensitivity of skin fibroblasts and the subcutaneous fibrosis, telangiectasia and skin erythema after radiotherapy. Radiother Oncol 1996;40:101–9.

    Google Scholar 

  83. Rudat V, Dietz A, Conradt C, Weber KJ, Flentje M. In vitro radiosensitivity of primary human fibroblasts. Lack of correlation with acute radiation toxicity in patients with head and neck cancer. Radiother Oncol 1997;43:181–8.

    Google Scholar 

  84. Leong T, Borg M, McKay M. Clinical and cellular radiosensitivity in inherited human syndromes. Clin Oncol (R Coll Radiol) 2004;16:206–9.

    Google Scholar 

  85. Johansen J, Bentzen SM, Overgaard J, Overgaard M. Evidence for a positive correlation between in vitro rediosensitivity of normal human skin fibroblasts and the occurrence of subcutaneous fibrosis after radiotherapy. Int J Radiat Biol 1994;66:407–12.

    Google Scholar 

  86. Beck-Bornhold HP. Intrinsic radiosensitivity of human fibroblasts seems to be unable to predict normal tissue response to radiotherapy. Int J Radiat Oncol Biol Phys 1995;32:553–4.

    Google Scholar 

  87. Elyan SG, West CML, Roberts SA, Hunter RD. Use of an internal standard in comparative measurements of the intrinsic radiosensitivities of human T-lymphocytes. Int J Radiat Biol 1993;64:385–91.

    Google Scholar 

  88. Scott D, Spreadborough A, Levine E, Roberts SA. Genetic predisposition in breast cancer. Lancet 1994;344:1444.

    Google Scholar 

  89. Elyan SAG, West CML, Roberts SA and Hunter RD. Use of low-dose rate irradiation to measure the intrinsic radiosensitivity of human T-lymphocytes. Int J Radiat Biol 1993;64:375–84.

    Google Scholar 

  90. Sabovljev SA, Cramp WA, Lewis PD, Harris G, Halnan KE, Lambert J. Use of rapid test of cellular radiosensitivity in radiotherapeutic practice. Lancet 1985;2:787.

    Google Scholar 

  91. Dunst J, Gebhart E. Unexpected tumor response, radiation myelitis and increased in vitro radio-sensitivity of lymphocytes in a patient with a non-small lung cancer. Radiother Oncol 1995;36:158.

    Google Scholar 

  92. Brown JM, Evans J, Kovacs MS. The prediction of human tumor radiosensitivity in situ: an approach using chromosome aberrations detected by fluorescence in situ hybridization. Int J Radiat Oncol Biol Phys 1992;24:279–86.

    Google Scholar 

  93. Badie C, Iliakis G, Foray N, Alsbeih G, Pantellias GE, Okayasu R et al. Defective repair of DNA double strand breaks and chomosome damage in fibroblasts from a radiosensitive leukemia patient. Cancer Res 1995;55:1232–4.

    Google Scholar 

  94. Neubauer S, Dunst J, Gebhart E. The impact of complex chromosomal rearrangements on the detection of cancer patients. Radiother Oncol 1997;43:189–95.

    Google Scholar 

  95. Rothfuss A, Schutz P, Bochum S, Volm T, Eberhardt E, Kreienberg R, et al. Induced micronucleus in peripheral lymphocytes as a screening test for carriers of a BRCA1 mutation in breast cancer families. Cancer Res 2000;60:390–4.

    Google Scholar 

  96. Slonina D, Klinek M, Szpytma T and Gasinska A. Comparison of normal tissue cells with normal tissue reactions after radiotherapy. Int J Radiat Biol 2000;76:1255–64.

    Google Scholar 

  97. Leong T, Whitty J, Keilar M, Mifsud S, Ramsay J, Birrell G, et al. Mutation analysis of BRCA1 and BRCA2 cancer predisposition genes in radiation hypersensitivity cancer patients. Int J Radiat Oncol Biol Phys 2000;48:959–65.

    Google Scholar 

  98. Price EA, Bourne SL, Radbourne R, Lawton PA, Lamerdin J, Thompson LH, et al. Rare microsatellite polymorphisms in DNA repair genes XRCC1, XRCC3 and XRCC5 associated with cancer in patients of varying radiosensitivity. Somatic Cell Mol Genet 1997;23:237–47.

    Google Scholar 

  99. Catena C, Parasacchi P, Conti D, Sgura A, Trenta G, Righi E, et al. Peripheral blood lymphocyte decrease and micronucleus yields during radiotherapy. Int J Radiat Biol 1997;72:575–85.

    Google Scholar 

  100. Di Giorgio M, Sardi M, Busto E, Vallerga MB, Taja MR, Mairal L. Assessment of individual radiosensitivity in human lymphocytes using micronucleus and microgel electrophoresis “Comet” assays. In: Proceedings of the 11th international congress of the International Radiation Protection Association (IRPA-11), 23–28 May 2004, Madrid.

  101. Lee T-K, Allison RR, O’Brien KF, Johnke RM, Christie KI, Naves JL, et al. Lymphocyte radiosensitivity correlated with pelvic radiotherapy morbidity. Int J Radiat Oncol Biol Phys 2003;57:222–9.

    Google Scholar 

  102. Leprat F, Alapetite C, Rosselli F, Ridet A, Schlumberger M, Sarasin A, et al. Impaired DNA repair as assessed by the “comet” assay in patients with thyroid tumors after a history of radiation therapy; a preliminary study. Int J Radiat Oncol Biol Phys 1998;40:1019–26.

    Google Scholar 

  103. McCurdy D, Tai LQ, Frias S, Wang Z. Delayed repair of DNA damage by ionizing radiation in cells from patients with systemic lupus erythematosus and rheumatoid arthritis. Radiat Res 1997;147:48–54.

    Google Scholar 

  104. Alapetite C, Thirion P, de la Rochefordiere A, Cosset JM, Moustacchi E. Analysis by alkaline comet assay of cancer patients with severe reactions to radiotherapy: defective rejoining of radioinduced DNA strand breaks in lymphocytes of breast cancer patients. Int J Cancer 1999;83:83–90.

    Google Scholar 

  105. Zhang H, Buchholz TA, Hancock D, Spitz MR, Wu X. Gamma induced single cell DNA damage as a measure of susceptibility to lung cancer: a preliminary report. Int J Oncol 2000;2:399–404.

    Google Scholar 

  106. Schindewolf C, Lobenwein K, Trinczek K, Gomolka M, Soewarto D, Fella C, et al. Comet assay as a tool for mouse models with inherited radiation sensitivity. Mamm Genome 2000;11:552–4.

    Google Scholar 

  107. Kiltie AE, Ryan AJ, Swindell R, Barber JBP, West CML, Magee B, et al. A correlation between residual radiation-induced double-strand breaks in cultured fibroblast and late radiotherapy reactions in breast cancer patients. Radiother Oncol 1999;51:55–65.

    Google Scholar 

  108. Kiltie AE, Barber JB, Swindell R, Ryan AJ, West CM, Hendry JH, et al. Lack of correlation between residual radiation-induced DNA damage, in keratinocytes assayed directly from skin, and late radiotherapy reactions in breast cancer patients. Int J Radiat Oncol Biol Phys 1999;43:481–7.

    Google Scholar 

  109. Andreassen CN, Alsner J, Overgaard J. Does variability in normal tissue reactions after radiotherapy have a genetic basis—where and how to look for it? Radiother Oncol 2002;64:131–40.

    Google Scholar 

  110. Andreassen CN, Alsner J, Overgaard M, Overgaard J. Prediction of normal tissue radiosensitivity from polymorphisms in candidate genes. Radiother Oncol 2003;69:127–35.

    Google Scholar 

  111. Duchaud E, Ridet A, Stoppa-Lyonnet D, Janin N, Moustacchi E, Rosselli F. Deregulated apoptosis in ataxia telangiectasia: association with clinical stigmata and radiosensitivity. Cancer Res 1996;56:1400–4.

    Google Scholar 

  112. Ozsahin M, Ozsahin H, Shi Y, Larsson B, Würgler FE, Crompton NEA. Rapid assay of intrinsic radiosensitivity based on apoptosis in human CD4 and CD8 T-lymphocytes. Int J Radiat Oncol 1997;38:429–40.

    Google Scholar 

  113. Ozsahin M, Miralbell R, Emery GC, Shi Y, Wellmann D, Coucke PA, et al. Profils apoptotiques altérés chez les patients irradiés montrant une hypersensibilité. Cancer Radiothér 1998;2:550.

    Google Scholar 

  114. Rached E, Schindler R, Beer KT, Vetterli D, Greiner RH. No predictive value of the micronucleus assay for patients with severe acute reaction of normal tissue after radiotherapy. Eur J Cancer 1998;34:378–83.

    Google Scholar 

  115. Li Ch, Wilson PB, Levine E, Barber J, Stewart A, Kumar S. TGF-β1 levels in pre-treatment plasma identify breast cancer patients at risk of developing post-radiotherapy fibrosis. Int J Cancer (Pred Oncol) 1999;84:155–9.

    Google Scholar 

  116. Annals of the International Commission on Radiological Protection. ICRP Publication No. 79: genetic susceptibility to cancer. Elmsford: Pergamon; 1998.

  117. Kony SJ, de Vathaire F, Chompret A, Shamsaldim A, Grimaud E, Raquin MA, et al. Radiation and genetic factors in the risk of second malignant neoplasms after a first cancer in childhood. Lancet 1997;350:91–5.

    Google Scholar 

Download references

Acknowledgements

The authors are grateful to Alicia Carregado for her assistance in the literature research.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michel H. Bourguignon.

Additional information

Part I of this review article is available at http://dx.doi.org/10.1007/s00259-004-1730-7

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bourguignon, M.H., Gisone, P.A., Perez, M.R. et al. Genetic and epigenetic features in radiation sensitivity. Eur J Nucl Med Mol Imaging 32, 351–368 (2005). https://doi.org/10.1007/s00259-004-1731-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-004-1731-6

Keywords

Navigation