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      New models for prediction of micronuclei formation in nuclear medicine department workers

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          Abstract

          Background

          Ionizing radiation causes detrimental health effects such as cancer and genetic damage. The study aim was to determine predictors for micronuclei (MN) occurrence and frequency in peripheral blood lymphocytes of health workers professionally exposed to radiation.

          Methods

          Health workers, age matched, selected for the study on regular check-ups, were divided according to the radiation exposure. The exposed group involved nuclear medicine department employees (54) and the control group comprised workers from other departments (36). Data about workers characteristics and habits, received annual doses (AD), total years of service (TYS) and exposed years of service (EYS) were taken from each subject. Blood samples were taken and micronuclei (MN) number in peripheral blood lymphocytes was calculated using CBMN assay according to standard protocols.

          Results

          Most workers were female, technicians, with mean age of 45.67 years and EYS about 15 years. Health workers exposed to radiation had significantly more MN than controls ( p = 0.001). Female gender, older age, higher received annual doses, longer EYS and TYS increased the MN number. Technicians and laboratory workers have higher risk for MN occurrence. Significant predictors of MN formation according to constructed model were workers age, sex, AD and EYS. One EYS year increases MN frequency 1.017 times, while receiving 0.1 mSy raises MN frequency by 26 %. EYS accurately predicts 86.30 % of MN frequencies and AD 64.60 %.

          Conclusions

          The model, developed for the first time in this study, showed that received annual doses and duration of exposure to radiation can be used for prediction of MN numbers.

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          Most cited references 20

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          The in vitro micronucleus technique.

          The study of DNA damage at the chromosome level is an essential part of genetic toxicology because chromosomal mutation is an important event in carcinogenesis. The micronucleus assays have emerged as one of the preferred methods for assessing chromosome damage because they enable both chromosome loss and chromosome breakage to be measured reliably. Because micronuclei can only be expressed in cells that complete nuclear division a special method was developed that identifies such cells by their binucleate appearance when blocked from performing cytokinesis by cytochalasin-B (Cyt-B), a microfilament-assembly inhibitor. The cytokinesis-block micronucleus (CBMN) assay allows better precision because the data obtained are not confounded by altered cell division kinetics caused by cytotoxicity of agents tested or sub-optimal cell culture conditions. The method is now applied to various cell types for population monitoring of genetic damage, screening of chemicals for genotoxic potential and for specific purposes such as the prediction of the radiosensitivity of tumours and the inter-individual variation in radiosensitivity. In its current basic form the CBMN assay can provide, using simple morphological criteria, the following measures of genotoxicity and cytotoxicity: chromosome breakage, chromosome loss, chromosome rearrangement (nucleoplasmic bridges), cell division inhibition, necrosis and apoptosis. The cytosine-arabinoside modification of the CBMN assay allows for measurement of excision repairable lesions. The use of molecular probes enables chromosome loss to be distinguished from chromosome breakage and importantly non-disjunction in non-micronucleated binucleated cells can be efficiently measured. The in vitro CBMN technique, therefore, provides multiple and complementary measures of genotoxicity and cytotoxicity which can be achieved with relative ease within one system. The basic principles and methods (including detailed scoring criteria for all the genotoxicity and cytotoxicity end-points) of the CBMN assay are described and areas for future development identified.
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            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.
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              Radiation-induced genomic instability and its implications for radiation carcinogenesis.

              Radiation-induced genomic instability is characterized by an increased rate of genetic alterations including cytogenetic rearrangements, mutations, gene amplifications, transformation and cell death in the progeny of irradiated cells multiple generations after the initial insult. Chromosomal rearrangements are the best-characterized end point of radiation-induced genomic instability, and many of the rearrangements described are similar to those found in human cancers. Chromosome breakage syndromes are defined by chromosome instability, and individuals with these diseases are cancer prone. Consequently, chromosomal instability as a phenotype may underlie some fraction of those changes leading to cancer. Here we attempt to relate current knowledge regarding radiation-induced chromosome instability with the emerging molecular information on the chromosome breakage syndromes. The goal is to understand how genetic and epigenetic factors might influence the onset of chromosome instability and the role of chromosomal instability in carcinogenesis.
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                Author and article information

                Contributors
                +381 11 366 3769 , sanjamaricic@yahoo.com
                milalex@eunet.rs
                enadot@yubc.net
                rakicboban@yahoo.co.uk
                terzicmilan@yahoo.co.uk
                Journal
                J Occup Med Toxicol
                J Occup Med Toxicol
                Journal of Occupational Medicine and Toxicology (London, England)
                BioMed Central (London )
                1745-6673
                25 July 2015
                25 July 2015
                2015
                : 10
                Affiliations
                [ ]Occupational Health Department, General Health Center “Savski Venac”, Pasterova 1, Belgrade, Serbia
                [ ]Institute of Occupational Medicine and Radiological Protection, Deligradska 29, Belgrade, Serbia
                [ ]School of Medicine, University of Belgrade, Dr Subotica 8, Belgrade, Serbia
                [ ]Clinic of Obstetrics and Gynecology, Clinical Center of Serbia, Dr Koste Todorovica 26, Belgrade, Serbia
                Article
                66
                10.1186/s12995-015-0066-5
                4513963
                © Terzic et al. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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                © The Author(s) 2015

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