The micronucleus assay as a biological dosimeter of in vivo ionising radiation exposure.

Biological dosimetry, based on the analysis of micronuclei (MN) in the cytokinesis-block micronucleus (CBMN) assay can be used as an alternative method for scoring dicentric chromosomes in the field of radiation protection. Biological dosimetry or Biodosimetry, is mainly performed, in addition to physical dosimetry, with the aim of individual dose assessment. Many studies have shown that the number of radiation-induced MN is strongly correlated with dose and quality of radiation. The CBMN assay has become, in the last years, a thoroughly validated and standardised technique to evaluate in vivo radiation exposure of occupational, medical and accidentally exposed individuals. Compared to the gold standard, the dicentric assay, the CBMN assay has the important advantage of allowing economical, easy and quick analysis. The main disadvantage of the CBMN assay is related to the variable micronucleus (MN) background frequency, by which only in vivo exposures in excess of 0.2-0.3 Gy X-rays can be detected. In the last years, several improvements have been achieved, with the ultimate goals (i) of further increasing the sensitivity of the CBMN assay for low-dose detection by combining the assay with a fluorescence in situ hybridisation centromere staining technique, (ii) of increasing the specificity of the test for radiation by scoring nucleoplasmic bridges in binucleated cells and (iii) of making the assay optimally suitable for rapid automated analysis of a large number of samples, viz. in case of a large-scale radiation accident. The development of a combined automated MN-centromere scoring procedure remains a challenge for the future, as it will allow systematic biomonitoring of radiation workers exposed to low-dose radiation.

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

[2]  H. Thierens,et al.  MICRONUCLEUS ASSAY REVEALS NO RADIATION EFFECTS AMONG NUCLEAR POWER PLANT WORKERS , 2002, Health physics.

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

[4]  Richard Wilkins,et al.  Micronuclei Induction in Human Fibroblasts Exposed In Vitro to Los Alamos High-Energy Neutrons , 2007 .

[5]  Yong Li,et al.  The cytokinesis-block micronucleus assay as a biological dosimeter for targeted alpha therapy , 2008, Physics in medicine and biology.

[6]  Elizabeth A Ainsbury,et al.  DOSE ESTIMATION SOFTWARE FOR RADIATION BIODOSIMETRY , 2010, Health physics.

[7]  L. Antunes,et al.  Cytogenetic analysis in lymphocytes from workers occupationally exposed to low levels of ionizing radiation. , 2007, Environmental toxicology and pharmacology.

[8]  H. Thierens,et al.  In vitro micronucleus-centromere assay to detect radiation-damage induced by low doses in human lymphocytes. , 1997, International journal of radiation biology.

[9]  G. Iliakis,et al.  Mechanisms of DNA double strand break repair and chromosome aberration formation , 2004, Cytogenetic and Genome Research.

[10]  M. Fenech Cytokinesis-block micronucleus cytome assay , 2007, Nature Protocols.

[11]  W. Vogel,et al.  An automated scoring procedure for the micronucleus test by image analysis. , 2004, Mutagenesis.

[12]  Laurence Roy,et al.  CABAS: a freely available PC program for fitting calibration curves in chromosome aberration dosimetry. , 2007, Radiation protection dosimetry.

[13]  M. Fenech,et al.  Nucleoplasmic bridges are a sensitive measure of chromosome rearrangement in the cytokinesis-block micronucleus assay. , 2003, Mutagenesis.

[14]  Aleksandra Fucic,et al.  Automated image analysis of cytokinesis-blocked micronuclei: an adapted protocol and a validated scoring procedure for biomonitoring. , 2008, Mutagenesis.

[15]  H. Braselmann,et al.  Use of Micronuclei in Biological Dosimetry of Absorbed Radiation Dose , 1990 .

[16]  M. Fenech Cytokinesis-block micronucleus assay evolves into a "cytome" assay of chromosomal instability, mitotic dysfunction and cell death. , 2006, Mutation research.

[17]  H. Thierens,et al.  Scoring of radiation-induced micronuclei in cytokinesis-blocked human lymphocytes by automated image analysis. , 1994, Cytometry.

[18]  M. Fenech,et al.  The cytokinesis-block micronucleus technique: a detailed description of the method and its application to genotoxicity studies in human populations. , 1993, Mutation research.

[19]  S. Bonassi,et al.  Micronuclei frequency in peripheral blood lymphocytes of cancer patients: a meta-analysis. , 2008, Mutation research.

[20]  H. Thierens,et al.  Patient dosimetry for 131I-lipiodol therapy , 2003, European Journal of Nuclear Medicine and Molecular Imaging.

[21]  D. Cimini,et al.  Analysis of chromosome loss and non-disjunction in cytokinesis-blocked lymphocytes of 24 male subjects. , 1999, Mutagenesis.

[22]  M. Fenech,et al.  Folate, vitamin B12, homocysteine status and DNA damage in young Australian adults. , 1998, Carcinogenesis.

[23]  H. Thierens,et al.  Micronucleus induction in peripheral blood lymphocytes of patients under radiotherapy treatment for cervical cancer or Hodgkin's disease. , 1995, International journal of radiation biology.

[24]  H. Elson,et al.  Effect of in vivo exposure to iodine-131 on the frequency and persistence of micronuclei in human lymphocytes. , 1993, Journal of toxicology and environmental health.

[25]  Elizabeth A Ainsbury,et al.  Biodosimetric tools for a fast triage of people accidentally exposed to ionising radiation. Statistical and computational aspects. , 2009, Annali dell'Istituto superiore di sanita.

[26]  E D Léonard,et al.  Usefulness and limits of biological dosimetry based on cytogenetic methods. , 2005, Radiation protection dosimetry.

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

[28]  H. Thierens,et al.  Cytogenetic monitoring of hospital workers occupationally exposed to ionizing radiation using the micronucleus centromere assay. , 2000, Mutagenesis.

[29]  H. Norppa,et al.  Detection of whole chromosomes in micronuclei of cytokinesis-blocked human lymphocytes by antikinetochore staining and in situ hybridization. , 1993, Mutagenesis.

[30]  Ş. Parlar,et al.  The Effects of Micronuclei with Whole Chromosome on Biological Dose Estimation , 2008 .

[31]  H. Braselmann,et al.  Detection of centromeres in vinblastine‐ and radiation‐induced micronuclei of human lymphocytes using FISH with an α satellite pancentromeric DNA probe , 1996, Environmental and molecular mutagenesis.

[32]  M. Fenech,et al.  HUman MicroNucleus project: international database comparison for results with the cytokinesis‐block micronucleus assay in human lymphocytes: I. Effect of laboratory protocol, scoring criteria, and host factors on the frequency of micronuclei , 2001, Environmental and molecular mutagenesis.

[33]  M. Kirsch‐Volders,et al.  Inter-laboratory comparison of cytogenetic endpoints for the biomonitoring of radiological workers. , 1999, International journal of radiation biology.

[34]  A. Vral,et al.  Sensitivity of micronucleus induction in human lymphocytes to low-LET radiation qualities: RBE and correlation of RBE and LET. , 1994, Radiation research.

[35]  S G Grant,et al.  Radiobiological evaluation of immigrants from the vicinity of Chernobyl. , 1997, International journal of radiation biology.

[36]  J. Slabbert,et al.  Assessment of the micronucleus assay as a biological dosimeter using cytokinesis-blocked lymphocytes from cancer patients receiving fractionated partial body-radiotherapy , 1998, Strahlentherapie und Onkologie.

[37]  H. Thierens,et al.  A cytogenetic study of radiological workers: effect of age, smoking and radiation burden on the micronucleus frequency. , 1996, Mutation research.

[38]  H. Norppa,et al.  Age-dependent inclusion of sex chromosomes in lymphocyte micronuclei of man. , 1998, American journal of human genetics.

[39]  P. Auquier,et al.  Cytogenetic monitoring by use of the micronucleus assay among hospital workers exposed to low doses of ionizing radiation. , 2007, Mutation research.

[40]  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.

[41]  T. Lörch,et al.  New developments in automated cytogenetic imaging: unattended scoring of dicentric chromosomes, micronuclei, single cell gel electrophoresis, and fluorescence signals , 2004, Cytogenetic and Genome Research.

[42]  I. Hayata,et al.  Cytogenetic damage in lymphocytes for the purpose of dose reconstruction: a review of three recent radiation accidents , 2004, Cytogenetic and Genome Research.

[43]  Hubert Thierens,et al.  Automated micronucleus (MN) scoring for population triage in case of large scale radiation events , 2010, International journal of radiation biology.

[44]  C. Streffer,et al.  The sensitivity of the in vitro cytokinesis-blocked micronucleus assay in lymphocytes for different and combined radiation qualities , 1998, Strahlentherapie und Onkologie.

[45]  Kai Rothkamm,et al.  γ-H2AX as protein biomarker for radiation exposure , 2009 .

[46]  P. Castelain,et al.  Automated detection of cytochalasin-B blocked binucleated lymphocytes for scoring micronuclei. , 1993, Mutagenesis.

[47]  Tung‐Kwang Lee,et al.  Micronuclei in lymphocytes of prostate cancer patients undergoing radiation therapy. , 2000, Mutation research.

[48]  M. Fenech,et al.  The HUman MicroNucleus Project--An international collaborative study on the use of the micronucleus technique for measuring DNA damage in humans. , 1999, Mutation research.

[49]  H. Thierens,et al.  Micronuclei induced by fast neutrons versus 60Co γ-rays in human peripheral blood lymphocytes , 1994 .

[50]  M. Fenech,et al.  Micronuclei in cytokinesis-blocked lymphocytes of cancer patients following fractionated partial-body radiotherapy. , 1990, International journal of radiation biology.

[51]  W. Denny,et al.  Three consistent patterns of response to substituted acridines in a variety of bacterial tester strains used for mutagenicity testing. , 1985, Mutation research.

[52]  A. Fucic,et al.  Genomic damage in children accidentally exposed to ionizing radiation: a review of the literature. , 2008, Mutation research.

[53]  A. Amaral,et al.  Dose assessment by quantification of chromosome aberrations and micronuclei in peripheral blood lymphocytes from patients exposed to gamma radiation , 2005 .

[54]  H. Thierens,et al.  A cytogenetic study of nuclear power plant workers using the micronucleus-centromere assay. , 1999, Mutation research.

[55]  M. Fenech,et al.  Cytokinesis-block micronucleus method in human lymphocytes: effect of in vivo ageing and low dose X-irradiation. , 1986, Mutation research.

[56]  M. Fenech,et al.  Measurement of micronuclei in lymphocytes. , 1985, Mutation research.

[57]  H. Thierens,et al.  Automated micronucleus (MN) scoring for population triage in case of large radiation accidents. , 2008 .

[58]  Kai Rothkamm,et al.  gamma-H2AX as protein biomarker for radiation exposure. , 2009, Annali dell'Istituto superiore di sanita.

[59]  H. Thierens,et al.  Polymorphisms in nonhomologous end‐joining genes associated with breast cancer risk and chromosomal radiosensitivity , 2008, Genes, chromosomes & cancer.

[60]  H. Thierens,et al.  Biological dosimetry using the micronucleus assay for lymphocytes: interindividual differences in dose response. , 1991, Health physics.