Journal of Biomedical Science

, Volume 15, Issue 5, pp 557–563 | Cite as

Biomarkers for human radiation exposure



There is a concern over the potential use of radioactive isotopes as a weapon of terror. The detonation of a radiation dispersal device, the so-called “dirty bomb” can lead to public panic. In order to estimate risks associated with radiation exposure, it is important to understand the biological effects of radiation exposure. Based on this knowledge, biomarkers to monitor potentially exposed populations after a radiological accident can be developed and would be extremely valuable for emergency response. While the traditional radiation exposure biomarkers based on cytogenetic assays serve as standard, the development of rapid and noninvasive tests for radiation exposure is needed. The genomics based knowledge is providing new avenues for investigation. The examination of gene expression after ionizing radiation exposure could serve as a potential molecular marker for biodosimetry. Microarray based studies are identifying new radiation responsive genes that could potentially be used as biomarkers of human exposure to radiation after an accident.


Biomarkers Biodosimetry Radiation effects 



The research in author’s laboratory is supported by grants from College of Nursing and Health Sciences, University of Vermont.


  1. 1.
    Unterweger MP, Pibida LS (2005) Advances in radiation detection technologies for responders. Health Phys 89:485–487PubMedCrossRefGoogle Scholar
  2. 2.
    Goans RE, Waselenko JK (2005) Medical management of radiological casualties. Health Phys 89:505–512PubMedCrossRefGoogle Scholar
  3. 3.
    Moulder JE (2004) Post-irradiation approaches to treatment of radiation injuries in the context of radiological terrorism and radiation accidents: a review. Int J Radiat Biol 80:3–10PubMedCrossRefGoogle Scholar
  4. 4.
    Oftedal P (1991) Biological low-dose radiation effects. Mutat Res 258:191–205PubMedGoogle Scholar
  5. 5.
    Breen AP, Murphy JA (1995) Reactions of oxyl radicals with DNA. Free Radic Biol Med 18:1033–1077PubMedCrossRefGoogle Scholar
  6. 6.
    Szumiel I (2008) Intrinsic radiation sensitivity: cellular signaling is the key. Radiat Res 169:249–258PubMedCrossRefGoogle Scholar
  7. 7.
    Valerie K, Yacoub A, Hagan MP, Curiel DT, Fisher PB, Grant S, Dent P (2007) Radiation-induced cell signaling: inside-out and outside-in. Mol Cancer Ther 6:789–801PubMedCrossRefGoogle Scholar
  8. 8.
    Lobrich M, Jeggo PA (2007) The impact of a negligent G2/M checkpoint on genomic instability and cancer induction. Nat Rev Cancer 7:861–869PubMedCrossRefGoogle Scholar
  9. 9.
    Weinfeld M, Rasouli-Nia A, Chaudhry MA, Britten RA (2001) Response of base excision repair enzymes to complex DNA lesions. Radiat Res 156:584–589PubMedCrossRefGoogle Scholar
  10. 10.
    Bailey SM, Bedford JS (2006) Studies on chromosome aberration induction: what can they tell us about DNA repair? DNA Repair (Amst) 5:1171–1181CrossRefGoogle Scholar
  11. 11.
    Borges HL, Linden R, Wang JY (2008) DNA damage-induced cell death: lessons from the central nervous system. Cell Res 18:17–26PubMedCrossRefGoogle Scholar
  12. 12.
    Fox MS, Klawansky S (2006) Interruption of cell transformation and cancer formation. Faseb J 20:2209–2213PubMedCrossRefGoogle Scholar
  13. 13.
    Elespuru RK, Sankaranarayanan K. (2007) New approaches to assessing the effects of mutagenic agents on the integrity of the human genome. Mutat Res 616:83–89PubMedGoogle Scholar
  14. 14.
    Chaudhry MA (2006) Bystander effect: biological endpoints and microarray analysis. Mutat Res 597:98–112PubMedGoogle Scholar
  15. 15.
    Greenberg MM (2007) Elucidating DNA damage and repair processes by independently generating reactive and metastable intermediates. Org Biomol Chem 5:18–30PubMedCrossRefGoogle Scholar
  16. 16.
    Shrivastav M, De Haro LP, Nickoloff JA (2008) Regulation of DNA double-strand break repair pathway choice. Cell Res 18:134–147PubMedCrossRefGoogle Scholar
  17. 17.
    Feinendegen LE (2002) Reactive oxygen species in cell responses to toxic agents. Hum Exp Toxicol 21:85–90PubMedCrossRefGoogle Scholar
  18. 18.
    Beckman KB, Ames BN (1997) Oxidative decay of DNA. J Biol Chem 272:19633–19636PubMedCrossRefGoogle Scholar
  19. 19.
    Hogg M, Wallace SS, Doublie S (2005) Bumps in the road: how replicative DNA polymerases see DNA damage. Curr Opin Struct Biol 15:86–93PubMedCrossRefGoogle Scholar
  20. 20.
    Blakely WF, Prasanna PG, Grace MB, Miller AC (2001) Radiation exposure assessment using cytological and molecular biomarkers. Radiat Prot Dosimetry 97:17–23PubMedGoogle Scholar
  21. 21.
    Hagmar L, Stromberg U, Tinnerberg H, Mikoczy Z (2001) The usefulness of cytogenetic biomarkers as intermediate endpoints in carcinogenesis. Int J Hyg Environ Health 204:43–47PubMedCrossRefGoogle Scholar
  22. 22.
    Thierens H, Vral A, Barbe M, Meijlaers M, Baeyens A, Ridder LD (2002) Chromosomal radiosensitivity study of temporary nuclear workers and the support of the adaptive response induced by occupational exposure. Int J Radiat Biol 78:1117–1126PubMedCrossRefGoogle Scholar
  23. 23.
    Prasanna PG, Hamel CJ, Escalada ND, Duffy KL, Blakely WF (2002) Biological dosimetry using human interphase peripheral blood lymphocytes. Mil Med 167:10–12PubMedGoogle Scholar
  24. 24.
    Trosko JE (1995) Biomarkers for low-level exposure causing epigenetic responses in stem cells. Stem Cells 13 Suppl 1:231–239PubMedGoogle Scholar
  25. 25.
    Grace MB, McLeland CB, Blakely WF (2002) Real-time quantitative RT-PCR assay of GADD45 gene expression changes as a biomarker for radiation biodosimetry. Int J Radiat Biol 78:1011–1021PubMedCrossRefGoogle Scholar
  26. 26.
    Pellmar TC, Rockwell S (2005) Priority list of research areas for radiological nuclear threat countermeasures. Radiat Res 163:115–123PubMedCrossRefGoogle Scholar
  27. 27.
    Blakely WF, Salter CA, Prasanna PG (2005) Early-response biological dosimetry-recommended countermeasure enhancements for mass-casualty radiological incidents and terrorism. Health Phys 89:494–504PubMedCrossRefGoogle Scholar
  28. 28.
    Natarajan AT, Boei JJ, Darroudi F, Van Diemen PC, Dulout F, Hande MP, Ramalho AT (1996) Current cytogenetic methods for detecting exposure and effects of mutagens and carcinogens. Environ Health Perspect 104(Suppl 3):445–448PubMedCrossRefGoogle Scholar
  29. 29.
    Palitti F, Pichierri P, Franchitto A, Proietti De Santis L, Mosesso P (1999) Chromosome radiosensitivity in human G2 lymphocytes and cell-cycle progression. Int J Radiat Biol 75:621–627PubMedCrossRefGoogle Scholar
  30. 30.
    Touil N., Aka PV, Buchet JP, Thierens H, Kirsch-Volders M (2002) Assessment of genotoxic effects related to chronic low level exposure to ionizing radiation using biomarkers for DNA damage and repair. Mutagenesis 17:223–232PubMedCrossRefGoogle Scholar
  31. 31.
    Sari-Minodier I, Orsiere T, Auquier P, Martin F, Botta A (2007) Cytogenetic monitoring by use of the micronucleus assay among hospital workers exposed to low doses of ionizing radiation. Mutat Res 629:111–121PubMedGoogle Scholar
  32. 32.
    Song EY, Rizvi SM, Qu CF, Raja C, Yuen J, Li Y, Morgenstern A, Apostolidis C, Allen BJ (2008) The cytokinesis-block micronucleus assay as a biological dosimeter for targeted alpha therapy. Phys Med Biol 53:319–328PubMedCrossRefGoogle Scholar
  33. 33.
    An MY, Kim TH (2002) Frequencies of micronuclei in peripheral lymphocytes in Korean populations after chronic low-dose radiation exposure. J Vet Sci 3:213–218PubMedGoogle Scholar
  34. 34.
    Vral A, Thierens H, Baeyens A, De Ridder L (2002) The micronucleus and G2-phase assays for human blood lymphocytes as biomarkers of individual sensitivity to ionizing radiation: limitations imposed by intraindividual variability. Radiat Res 157:472–477PubMedCrossRefGoogle Scholar
  35. 35.
    Edwards AA, Szluinska M, Lloyd DC (2007) Reconstruction of doses from ionizing radiation using fluorescence in situ hybridization techniques. Br J Radiol 80(Spec No 1):S63–S67PubMedCrossRefGoogle Scholar
  36. 36.
    Hlatky L, Sachs RK, Vazquez M, Cornforth MN (2002) Radiation-induced chromosome aberrations: insights gained from biophysical modeling. Bioessays 24:714–723PubMedCrossRefGoogle Scholar
  37. 37.
    Hittelman WN, Pandita TK (1994) Possible role of chromatin alteration in the radiosensitivity of ataxia-telangiectasia. Int J Radiat Biol 66:S109–S113PubMedCrossRefGoogle Scholar
  38. 38.
    Tucker JD (2001) Fish cytogenetics and the future of radiation biodosimetry. Radiat Prot Dosimetry 97:55–60PubMedGoogle Scholar
  39. 39.
    Savage JR (2002) Reflections and meditations upon complex chromosomal exchanges. Mutat Res 512:93–109PubMedCrossRefGoogle Scholar
  40. 40.
    Bender MA, Gooch PC (1966) Somatic chromosome aberrations induced by human whole-body irradiation: the “Recuplex” criticality accident. Radiat Res 29:568–582PubMedCrossRefGoogle Scholar
  41. 41.
    Hsieh WA, Ni C, Hwang JJ, Fang JS, Lin SP, Lin YA, Huang TW, Chang WP (2002) Evaluation of the frequencies of chromosomal aberrations in a population exposed to prolonged low dose-rate 60Co gamma-irradiation. Int J Radiat Biol 78:625–633PubMedCrossRefGoogle Scholar
  42. 42.
    Coco Martin JM, Mooren E, Ottenheim C, Burrill W, Nunez MI, Sprong D, Bartelink H, Begg AC (1999) Potential of radiation-induced chromosome aberrations to predict radiosensitivity in human tumour cells. Int J Radiat Biol 75:1161–1168PubMedCrossRefGoogle Scholar
  43. 43.
    Guerci AM, Grillo CA, Dulout FN, Seoane AI (2006) Assessment of genotoxic damage in lymphocytes of hospital workers exposed to ionizing radiation in Argentina. Arch Environ Occup Health 61:163–169PubMedCrossRefGoogle Scholar
  44. 44.
    Olive PL (2007) Impact of the comet assay in radiobiology. Mutat ResGoogle Scholar
  45. 45.
    Verde PE, Geracitano LA, Amado LL, Rosa CE, Bianchini A, Monserrat JM (2006) Application of public-domain statistical analysis software for evaluation and comparison of comet assay data. Mutat Res 604:71–82PubMedGoogle Scholar
  46. 46.
    Cadet J, Bellon S, Douki T, Frelon S, Gasparutto D, Muller E, Pouget JP, Ravanat JL, Romieu A, Sauvaigo S (2004) Radiation-induced DNA damage: formation, measurement, and biochemical features. J Environ Pathol Toxicol Oncol 23:33–43PubMedCrossRefGoogle Scholar
  47. 47.
    Popp W, Plappert U, Muller WU, Rehn B, Schneider J, Braun A, Bauer PC, Vahrenholz C, Presek P, Brauksiepe A, Enderle G, Wust T, Bruch J, Fliedner TM, Konietzko N, Streffer C, Woitowitz HJ, Norpoth K (2000) Biomarkers of genetic damage and inflammation in blood and bronchoalveolar lavage fluid among former German uranium miners: a pilot study. Radiat Environ Biophys 39:275–282PubMedCrossRefGoogle Scholar
  48. 48.
    Garaj-Vrhovac V, Kopjar N (2003) The alkaline comet assay as biomarker in assessment of DNA damage in medical personnel occupationally exposed to ionizing radiation. Mutagenesis 18:265–271PubMedCrossRefGoogle Scholar
  49. 49.
    Jaworska A, Wojewodzka M, De Angelis P (2002) Radiation sensitivity and the status of some radiation sensitivity markers in relatively sensitive lymphoid cells. Radiats Biol Radioecol 42:595–599PubMedGoogle Scholar
  50. 50.
    Boreham DR, Gale KL, Maves SR, Walker JA, Morrison DP (1996) Radiation-induced apoptosis in human lymphocytes: potential as a biological dosimeter. Health Phys 71:685–691PubMedCrossRefGoogle Scholar
  51. 51.
    Cucinotta FA, Dicello JF, Nikjoo H, Cherubini R (2002) Computational model of the modulation of gene expression following DNA damage. Radiat Prot Dosimetry 99:85–90PubMedGoogle Scholar
  52. 52.
    Bishay K, Ory K, Olivier MF, Lebeau J, Levalois C, Chevillard S (2001) DNA damage-related RNA expression to assess individual sensitivity to ionizing radiation. Carcinogenesis 22:1179–1183PubMedCrossRefGoogle Scholar
  53. 53.
    Miller AC, Luo L, Chin WK, Director-Myska AE, Prasanna PG, Blakely WF (2002) Proto-oncogene expression: a predictive assay for radiation biodosimetry applications. Radiat Prot Dosimetry 99:295–302PubMedGoogle Scholar
  54. 54.
    Amundson SA, Bittner M, Meltzer P, Trent J, Fornace AJ Jr (2001) Induction of gene expression as a monitor of exposure to ionizing radiation. Radiat Res 156:657–661PubMedCrossRefGoogle Scholar
  55. 55.
    Amundson SA, Do KT, Shahab S, Bittner M, Meltzer P, Trent J, Fornace AJ Jr (2000) Identification of potential mRNA biomarkers in peripheral blood lymphocytes for human exposure to ionizing radiation. Radiat Res 154:342–346PubMedCrossRefGoogle Scholar
  56. 56.
    Wiebalk K, Schmezer P, Kropp S, Chang-Claude J, Celebi O, Debus J, Bartsch H, Popanda O (2007) In vitro radiation-induced expression of XPC mRNA as a possible biomarker for developing adverse reactions during radiotherapy. Int J Cancer 121:2340–2345PubMedCrossRefGoogle Scholar
  57. 57.
    Sudprasert W, Navasumrit P, Ruchirawat M (2006) Effects of low-dose gamma radiation on DNA damage, chromosomal aberration and expression of repair genes in human blood cells. Int J Hyg Environ Health 209:503–511PubMedCrossRefGoogle Scholar
  58. 58.
    Kang CM, Park KP, Song JE, Jeoung DI, Cho CK, Kim TH, Bae S, Lee SJ, Lee YS (2003) Possible biomarkers for ionizing radiation exposure in human peripheral blood lymphocytes. Radiat Res 159:312–319PubMedCrossRefGoogle Scholar
  59. 59.
    Park WY, Hwang CI, Im CN, Kang MJ, Woo JH, Kim JH, Kim YS, Kim JH, Kim H, Kim KA, Yu HJ, Lee SJ, Lee YS, Seo JS (2002) Identification of radiation-specific responses from gene expression profile. Oncogene 21:8521–8528PubMedCrossRefGoogle Scholar
  60. 60.
    Goldberg Z, Schwietert CW, Lehnert B, Stern R, Nami I (2004) Effects of low-dose ionizing radiation on gene expression in human skin biopsies. Int J Radiat Oncol Biol Phys 58:567–574PubMedGoogle Scholar
  61. 61.
    Fachin AL, Mello SS, Sandrin-Garcia P, Junta CM, Donadi EA, Passos GA, Sakamoto-Hojo ET (2007) Gene expression profiles in human lymphocytes irradiated in vitro with low doses of gamma rays. Radiat Res 168:650–665PubMedCrossRefGoogle Scholar
  62. 62.
    Chaudhry MA (2006) Radiation-induced gene expression profile of human cells deficient in 8-hydroxy-2′-deoxyguanine glycosylase. Int J Cancer 118:633–642PubMedCrossRefGoogle Scholar

Copyright information

© National Science Council Taipei 2008

Authors and Affiliations

  1. 1.Department of Medical Laboratory and Radiation Sciences, College of Nursing and Health SciencesUniversity of VermontBurlingtonUSA

Personalised recommendations