Limitations Associated with Analysis of Cytogenetic Data for Biological Dosimetry

Abstract The scientific literature concerning cytogenetic biodosimetry has been reviewed to identify the range of scenarios of radiation exposure where biodosimetry has been carried out. Limitations in the existing standardized statistical methodology have been identified and categorized, and the reasons for these limitations have been explored. Statistical problems generally occur due to either low numbers of aberrations leading to large uncertainties or deviations in aberration-per-cell distributions leading to over- or under-dispersion with respect to the Poisson model. A number of difficulties also stem from limitations of the classical statistical methodology, which requires that chromosome aberration yields be considered as something “fixed” and thus provides a deterministic estimate of radiation dose and associated confidence limits (because an assignment of a probability to an event is based solely on the observed frequency of occurrence of the event). Therefore, it is suggested that solutions to the listed problems should be based in the Bayesian framework. This will allow the investigator to take a probabilistic approach to analysis of cytogenetic data, which can be considered highly appropriate for biological dose estimation.

[1]  A. Natarajan,et al.  Dose Assessments by Cytogenetic Analysis in the Goiania (Brazil) Radiation Accident , 1988 .

[2]  P. Horton,et al.  A comparison of physical and cytogenetic estimates of radiation dose in patients treated with iodine-131 for thyroid carcinoma. , 1976, International journal of radiation biology and related studies in physics, chemistry, and medicine.

[3]  John H. Jopson,et al.  A REPORT OF TWO CASES , 1902 .

[4]  Maznik Na,et al.  [The retrospective cytogenetic dosimetry using the results of conventional chromosomal analysis in Chernobyl clean-up workers]. , 2005 .

[5]  J. Podd,et al.  Elevated chromosome translocation frequencies in New Zealand nuclear test veterans , 2008, Cytogenetic and Genome Research.

[6]  D. Lloyd,et al.  Chromosomal aberrations in lymphocytes of residents of areas contaminated by radioactive discharges from the Chernobyl accident , 1995 .

[7]  M. Bender,et al.  Current status of cytogenetic procedures to detect and quantify previous exposures to radiation. , 1988, Mutation research.

[8]  Increased Frequency of Chromosome Translocations Associated with Diagnostic X-Ray Examinations , 2008, Radiation research.

[9]  A. Leonard,et al.  Persistence of Chromosome Aberrations in an Accidentally Irradiated Subject , 1988 .

[10]  V. Vicente,et al.  Biological dosimetry and Bayesian analysis of chromosomal damage in thyroid cancer patients. , 2007, Radiation protection dosimetry.

[11]  P. Zhou,et al.  Seventeen-year follow-up study on chromosomal aberrations in five victims accidentally exposed to several Gy of 60Co γ-rays , 2009, Radiation and environmental biophysics.

[12]  A. A. Gordeeva,et al.  Protracted overexposure to A 137Cs source : I. Dose reconstruction , 1999 .

[13]  R S Brame,et al.  Bayesian methods for chromosome dosimetry following a criticality accident. , 2003, Radiation protection dosimetry.

[14]  David C Lloyd,et al.  WHO 1st Consultation on the Development of a Global Biodosimetry Laboratories Network for Radiation Emergencies (BioDoseNet) , 2009, Radiation research.

[15]  D. Lloyd,et al.  A collaborative exercise on cytogenetic dosimetry for simulated whole and partial body accidental irradiation. , 1987, Mutation research.

[16]  D. Lloyd,et al.  Accidental intake of tritiated water: a cytogenetic follow-up case on translocation stability and dose reconstruction. , 1998, International journal of radiation biology.

[17]  I. Buraczewska,et al.  Chromosomal Aberrations and Micronuclei In Lymphocytes of Breast Cancer Patients after an Accident during Radiotherapy with 8 MeV Electrons1 , 2003, Radiation research.

[18]  D. Lloyd,et al.  Chromosomal aberrations in human lymphocytes induced in vitro by very low doses of X-rays. , 1992, International journal of radiation biology.

[19]  G. Stephan,et al.  Chromosome aberrations in human lymphocytes analysed by fluorescence in situ hybridization after in vitro irradiation, and in radiation workers, 11 years after an accidental radiation exposure. , 1997, International journal of radiation biology.

[20]  A. Heimers,et al.  Chromosome aberrations induced in human lymphocytes by in vitro and in vivo X-rays. , 2002, Mutation research.

[21]  H Thierens,et al.  Cytogenetic biodosimetry of an accidental exposure of a radiological worker using multiple assays. , 2005, Radiation protection dosimetry.

[22]  N A Maznik,et al.  [The retrospective cytogenetic dosimetry using the results of conventional chromosomal analysis in Chernobyl clean-up workers]. , 2005, Radiatsionnaia biologiia, radioecologiia.

[23]  J. G. Brewen,et al.  Radiation-induced human chromosome aberration yields following an accidental whole-body exposure to 60 Co -rays. , 1972, Radiation research.

[24]  M. I. Vorobiova,et al.  ELECTRON PARAMAGNETIC RESONANCE AND FLUORESCENCE IN SITU HYBRIDIZATION-BASED INVESTIGATIONS OF INDIVIDUAL DOSES FOR PERSONS LIVING AT METLINO IN THE UPPER REACHES OF THE TECHA RIVER , 2005, Health physics.

[25]  Maznik Na.  [Long-term follow-up cytogenetic survey and biological dosimetry in persons evacuated from 30-km Chernobyl NPP zone]. , 2004 .

[26]  A. Jaworska,et al.  Premature Chromosome Condensation (PCC) Assay for Dose Assessment in Mass Casualty Accidents , 2010, Radiation research.

[27]  G. Wolf,et al.  Cytogenetic investigations in flight personnel. , 1999, Radiation Protection Dosimetry.

[28]  L Roy,et al.  Study of the tools available in biological dosimetry to estimate the dose in cases of accidental complex overexposure to ionizing radiation: The Lilo accident , 2006, International journal of radiation biology.

[29]  D. Lloyd,et al.  Cytogenic investigations of serious overexposures to an industrial gamma radiography source. , 2002, Radiation protection dosimetry.

[30]  Sunghuen Kim,et al.  A Report of Two Cases , 2008 .

[31]  S. Gardner,et al.  The Cellular Lethality of Radiation-Induced Chromosome Translocations in Human Lymphocytes , 2002, Radiation research.

[32]  M. Sasaki,et al.  Cytogenetical dose estimation for 3 severely exposed patients in the JCO criticality accident in Tokai-mura. , 2001, Journal of radiation research.

[33]  M. Sasaki,et al.  Chromosomal biodosimetry by unfolding a mixed Poisson distribution: a generalized model , 2003, International journal of radiation biology.

[34]  P. Venkatachalam,et al.  Estimation of dose in cancer patients treated with fractionated radiotherapy using translocation, dicentrics and micronuclei frequency in peripheral blood lymphocytes. , 1999, Mutation research.

[35]  B. Liu,et al.  Biodosimetry estimate for high-LET irradiation , 2007, Radiation and environmental biophysics.

[36]  V. Durand,et al.  The cytogenetic dosimetry of recent accidental overexposure. , 2001, Cellular and molecular biology.

[37]  M. Benderitter,et al.  New Biological Indicators to Evaluate and Monitor Radiation-Induced Damage: An Accident Case Report , 2008, Radiation research.

[38]  A. Heimers,et al.  Chromosome aberration analysis and the influence of mitotic delay after simulated partial-body exposure with high doses of sparsely and densely ionising radiation , 2006, Radiation and environmental biophysics.

[39]  Li-Ping Jiang,et al.  Clinical report of three cases of acute radiation sickness from a (60)Co radiation accident in Henan Province in China. , 2008, Journal of radiation research.

[40]  C. Mesquita,et al.  Dose Estimation by Cytogenetic Analysis in a Radiation Accident with 137Cs in Goiania (Brazil): Evaluation of Probable Exposure Doses Range , 1990 .

[41]  H. Braselmann,et al.  Chromosome aberrations in nuclear power plant workers: the influence of dose accumulation and lymphocyte life-time. , 1994, Mutation research.

[42]  D. Chen,et al.  Dose-effect relationship of dicentric and ring chromosomes in lymphocytes of individuals living in the high background radiation areas in China. , 2000, Journal of radiation research.

[43]  THE MINIMUM DETECTABLE DOSE BY BIODOSIMETRY IN A RADIATION OVEREXPOSURE , 2006 .

[44]  T. Sugahara,et al.  Dose limits below which the effect of radiation on health becomes undetectable due to background variation. , 2008, Mutation research.

[45]  D. Lloyd,et al.  Criticality accident dosimetry by chromosomal analysis. , 2004, Radiation protection dosimetry.

[46]  U. Gössi,et al.  Accidental Intake of Tritiated Water: A Report of Two Cases , 1986 .

[47]  Marta Szłuińska,et al.  Statistical Methods for Biological Dosimetry , 2007 .

[48]  N. Takeichi,et al.  Unstable-type chromosome aberrations in lymphocytes from individuals living near Semipalatinsk nuclear test site. , 2006, Journal of radiation research.

[49]  M. Sasaki.  Cytogenetic biomonitoring of human radiation exposures: possibilities, problems and pitfalls. , 1992, Journal of radiation research.

[50]  W. Chang,et al.  Follow-up in the micronucleus frequencies and its subsets in human population with chronic low-dose gamma-irradiation exposure. , 1999, Mutation research.

[51]  J. Tucker.  Low-dose ionizing radiation and chromosome translocations: a review of the major considerations for human biological dosimetry. , 2008, Mutation research.

[52]  K Rothkamm,et al.  Interlaboratory Variation in Scoring Dicentric Chromosomes in a Case of Partial-Body X-Ray Exposure: Implications for Biodosimetry Networking and Cytogenetic “Triage Mode” Scoring , 2009, Radiation research.