Number Of Dicentric Chromosomes Research Articles

A Statistical Model for Count Data Analysis and Population Size Estimation: Introducing a Mixed Poisson–Lindley Distribution and Its Zero Truncation

Count data consists of both observed and unobserved events. The analysis of count data often encounters overdispersion, where traditional Poisson models may not be adequate. In this paper, we introduce a tractable one-parameter mixed Poisson distribution, which combines the Poisson distribution with the improved second-degree Lindley distribution. This distribution, called the Poisson-improved second-degree Lindley distribution, is capable of effectively modeling standard count data with overdispersion. However, if the frequency of the unobserved events is unknown, the proposed distribution cannot be directly used to describe the events. To address this limitation, we propose a modification by truncating the distribution to zero. This results in a tractable zero-truncated distribution that encompasses all types of dispersions. Due to the unknown frequency of unobserved events, the population size as a whole becomes unknown and requires estimation. To estimate the population size, we develop a Horvitz–Thompson-like estimator utilizing truncated distribution. Both the untruncated and truncated distributions exhibit desirable statistical properties. The estimators for both distributions, as well as the population size, are asymptotically unbiased and consistent. The current study demonstrates that both the truncated and untruncated distributions adequately explain the considered medical datasets, which are the number of dicentric chromosomes after being exposed to different doses of radiation and the number of positive Salmonella. Moreover, the proposed population size estimator yields reliable estimates.

Co-occurrence of acrocentric chromosome associations with dicentric chromosomes in irradiated human lymphocytes.

The occurrence of acrocentric chromosome association (ACA) after radiation exposure is an interesting cytogenetic endpoint, known to show adose-dependent increase in irradiated lymphocytes suggesting its potential use in radiation biodosimetry. Here, an attempt was made to study the complexity and correlation of the occurrence of ACA with dicentric chromosomes (DC) in lymphocytes exposed to gamma radiation. Ninety metaphases each with DC and without DC were chosen randomly from lymphocytes irradiated with different doses (0, 1, 2, 3, 4 and 5 Gy) of gamma radiation. ACA along with chromosomal types of aberrations were scored and analyzed for complexity and co-occurrence, retrospectively. The number of associations between 2and ≥ 3acrocentric chromosomes showed an increase with each irradiation dose. Concomitantly, the total number of chromosomal type of aberrations showed an increase in number at each radiation dose studied. The number of DC showed an increase, however, metaphases containing 1DC decreased while ≥ 2DC increased as the radiation dose increased. The number of tricentric chromosomes increased at doses higher than 2 Gy. Importantly, the association of DC with an acrocentric chromosome was noticed at doses 2 Gy and above. Asignificant (p < 0.05) increase was noticed in ACA frequency in 1DC and ≥ 2DC metaphases at 1and 2 Gy, in 1DC at 3 Gy, and in ≥ 2DC 4and 5 Gy compared to the frequency in no DC metaphases. When average ACA frequency was plotted against DC frequency, asignificant (p = 0.0009) correlation was observed, producing regression equation y = 0.9025x + 0.1283; R2 = 0.9522. The present analysis showed increasing ACA complexity with increasing radiation dose. Furthermore, ahigher frequency of ACA in cells with 1DC or ≥ 2DC compared to the ACA in cells without DC from the same sample of irradiated lymphocytes demonstrated the co-occurrence of ACA and DC in the same cells.

Dose Variations Using an X-Ray Cabinet to Establish in vitro Dose-Response Curves for Biological Dosimetry Assays.

In biological dosimetry, dose-response curves are essential for reliable retrospective dose estimation of individual exposure in case of a radiation accident. Therefore, blood samples are irradiated in vitro and evaluated based on the applied assay. Accurate physical dosimetry of the irradiation performance is a critical part of the experimental procedure and is influenced by the experimental setup, especially when X-ray cabinets are used. The aim of this study was to investigate variations and pitfalls associated with the experimental setups used to establish calibration curves in biological dosimetry with X-ray cabinets. In this study, irradiation was performed with an X-ray source (195 kV, 10 mA, 0.5 mm Cu filter, dose rate 0.52 Gy/min, 1st and 2nd half-value layer = 1.01 and 1.76 mm Cu, respectively, average energy 86.9 keV). Blood collection tubes were irradiated with a dose of 1 Gy in vertical or horizontal orientation in the center of the beam area with or without usage of an additional fan heater. To evaluate the influence of the setups, physical dose measurements using thermoluminescence dosimeters, electron paramagnetic resonance dosimetry and ionization chamber as well as biological effects, quantified by dicentric chromosomes and micronuclei, were compared. This study revealed that the orientation of the sample tubes (vertical vs. horizontal) had a significant effect on the radiation dose with a variation of −41% up to +49% and contributed to a dose gradient of up to 870 mGy inside the vertical tubes due to the size of the sample tubes and the associated differences in the distance to the focal point of the tube. The number of dicentric chromosomes and micronuclei differed by ~30% between both orientations. An additional fan heater had no consistent impact. Therefore, dosimetric monitoring of experimental irradiation setups is mandatory prior to the establishment of calibration curves in biological dosimetry. Careful consideration of the experimental setup in collaboration with physicists is required to ensure traceability and reproducibility of irradiation conditions, to correlate the radiation dose and the number of aberrations correctly and to avoid systematical bias influencing the dose estimation in the frame of biological dosimetry.

Molecular cytogenetic analysis of dicentric chromosomes in acute myeloid leukemia

Dicentric chromosomes (DCs) have been described in many hematological diseases, including acute myeloid leukemia (AML). They are markers of cancer and induce chromosomal instability, leading to the formation of other chromosomal aberrations and the clonal evolution of pathological cells. Our knowledge of the roles and behavior of human DCs is often derived from studies of induced DCs and cell lines. It is difficult to identify all the DCs in the karyotypes of patients because of the limitations of metaphase cytogenetic methods. The aim of this study was to revise the karyotypes of 20 AML patients in whom DCs were found with conventional G-banding or multicolor fluorescence in situ hybridization (mFISH) with (multi)centromeric probes and to characterize the DCs at the molecular cytogenetic level. FISH analyses confirmed 23 of the 29 expected DCs in 18 of 20 patients and identified 13 others that had not been detected cytogenetically. Fourteen DCs were altered by other chromosomal changes. In conclusion, karyotypes with DCs are usually very complex, and we have shown that they often contain more than one DC, which can be missed with conventional or mFISH methods. Our study indicates an association between number of DCs in karyotype and very short survival of patients.

Quantitation of Chromosome Damage by Imaging Flow Cytometry.

Biodosimetry is a method for measuring the dose of radiation to individuals using biological markers such as chromosome damage. Following mass casualty events, it is important to provide this information rapidly in order to assist with the medical management of potentially exposed casualties. Currently, the gold standard for biodosimetry is the dicentric chromosome assay, which accurately estimates the dose from the number of dicentric chromosomes in lymphocytes. To increase throughput of analysis following a large-scale mass casualty event, this assay has been adapted for use on the imaging flow cytometer. This chapter describes the methods for the identification and quantification of mono- and multicentric chromosomes using the imaging flow cytometer.

Dicentric Chromosome Assay: A Potential In Vitro Biomarker for Radiosensitivity

Dicentric Chromosome Assay (DCA) is a validated biodosimetry technique. It has been used to determine previous exposure to radiation by measuring chromosome damage in Tcells that have lifespan of about 3 years. Association of increased background dicentric chromosomes (DC) and risk of cancer development has been reported before. Previously, we reported results supporting radiation induced DC and excess fragments (EF) as potential biomarkers of increased radiosensitivity. In this study we studied number of DCs and EFs in a cohort of cancer patients cancer to assess that as a marker of cancer susceptibility.

Biological dosimetry after radiosynoviorthesis with rhenium-186 sulphide and erbium-169 citrate

Radiosynoviorthesis (RSO) with the nuclides rhenium-186 sulphide (186Re) and erbium-169 citrate (169Er) is an established concept for the treatment of persistent synovitis of medium and small sized joints. THE AIM of the present studies was to investigate the biological radiation effect based on analysing chromosome aberrations. Immediately before and 17 to 19 days (186Re) or 45 to 50 (169Er) days after RSO with 186Re or 169Er colloid and subsequent immobilisation of the treated joint, blood samples of a total of 23 patients were collected. The yield of dicentric chromosomes in lymphocytes was determined exclusively in metaphases of the first cell cycle in vitro. In addition, for 186Re the activity leakage was measured three days after RSO by whole-body scintigraphy. No statistically significant increase in the number of dicentric chromosomes (40 and 88 before and 59 and 105 after treatment with 186Re and 169Er, respectively) in a total of 47017 cells analysed from 46 blood samples could be found as a result of RSO. For 186Re an activity leakage of 3.9%±7% with a maximum of 23.4% corresponding to an effective dose of 2.8±4.5 mSv , respectively 13.8 mSv, was determined. Also in the case of the maximum leakage no significant increase of dicentric chromosomes were detected. No significant biological radiation effect can be detected after RSO with 186Re and 169Er, also in cases of high leakage. Therefore, RSO can be classified as a save therapeutic procedure without a relevant radiation risk.

Biological dosimetry after yttrium-90 citrate colloid radiosynoviorthesis

Radiosynoviorthesis (RSO) with the ss-particle-emitting nuclide yttrium-90 is an established concept for the treatment of persistent synovitis of the knee joint. The AIM of this study was to investigate the biological radiation effect on the basis of a characteristic radiation parameter. After RSO procedures with yttrium-90 citrate colloid and subsequent immobilisation of the knee, blood specimens of 10 patients were collected immediately before RSO and 11 to 13 days after the intervention. The yield of dicentric chromosomes in the lymphocytes was determined exclusively in metaphases of the first cell cycle in vitro. In addition, activity leakage was measured by wholebody bremsstrahlung-scintigraphy. No statistically significant increase in the number of dicentric chromosomes (26 before treatment and 34 after treatment) in 20 192 cells analyzed from the 20 blood samples could be found as a result of RSO. However, the analysis of at least 1000 cells per blood sample demonstrates a tendency for a biological radiation effect in the blood of patients on the basis of this characteristic radiation parameter. Two of the 10 RSO patients had undergone a second RSO using yttrium-90 citrate, whereby one patient displayed activity transport out of the knee joint, amounting to 6 MBq. Only for him a radiation effect (about 130 mGy per single RSO) could be calculated by biological dosimetry. Since in general, based on the analysis of dicentric chromosomes in at least 1000 lymphocytes per individual, detection limits for groups of persons after long-term exposures to low-LET radiation of 50-100 mGy are possible, we assume that RSO with yttrium-90 should be associated with a low whole-body radiation exposure.

Chromosome Aberrations Induced in Human Lymphocytes by 3.45 MeV Alpha Particles Analyzed by Premature Chromosome Condensation

Premature chromosome condensation (PCC) experiments using human lymphocytes with centromere staining have shown that after exposure to 3.45 MeV alpha-particle radiation, the full number of dicentric chromosomes appears when the cell fusion protocol is applied immediately after irradiation. In this case, the time available for repair and misrepair of DNA damage is only about 30 min. The number of dicentrics does not change with a further increase in the time available for chromatin rearrangement. This fast response confirms the expectation based on our previous experiments using PCC with 150 kV X rays in which the alpha component of the yield of dicentrics was found to appear when the cell fusion protocol was applied immediately after irradiation, whereas the beta component was delayed by several hours. The time constant for rejoining of the excess acentric chromosome fragments is found to be donor-specific and not to differ for alpha particles and X rays, but alpha-particle radiation leaves a larger fraction of the excess acentric fragments unrejoined. The RBEs of the 3.45 MeV alpha-particle radiation compared to 150 kV X rays, evaluated for the alpha component for the yield of dicentrics and for the yield of unrepaired acentric fragments, have almost equal values of about 4. This is consistent with data in the literature on chromosome aberrations observed in metaphase that show the equality of the RBE values for production of dicentrics and acentric fragments. Our experimental results concerning the fast kinetics of the alpha component of the yield of exchange-type chromosome aberrations are not consistent with Lea's pairwise lesion interaction model, and they support the proposed alternative mechanism of lesion-nonlesion interaction between chromatin regions carrying clustered DNA damage and intact chromatin regions.

Chromosome Aberration Analysis in Aircrew Members

Aircrew members on high altitude flights are exposed to cosmic radiation. Investigations are required to decide whether they should be classified as occupationally exposed persons and subjected to radiation protection. Physical measurements of the cosmic radiation field are quite difficult due to uncertainties in various exposure components and their variations. In this study biological dosemeters, i.e. dicentric chromosomes, are used as appropriate indicators in determining the exposure of flight personnel. Nine individuals were investigated for chromosome aberrations. For this purpose, lymphocyte cultures and slide preparations were made according to standard cell cycle controlling methods (fluorescence plus Giemsa staining). The elevated number of dicentric chromosomes and their intercellular distribution provide evidence that the individuals investigated had indeed been exposed to high LET irradiation.

Microcirculatory disturbances in the early period of autotoxic shock

Telomeric fusion of metaphase chromosomes was studied in conditions of DNA hypomethylation induced with 5-azacytidine. It was shown that the increased number of dicentric chromosomes was statistically significant in experiments when 5-azacytidine was used together with colcemid and 5-bromodeoxyuridine. These data demonstrate that DNA hypomethylation plays an important role in the manifestation of this phenomenon.

Chromosome-exchange aberrations in human lymphocytes.

SummaryThe probability of finding a given chromosome in a dicentric is directly proportional to the length of that chromosome at interphase, but not to the length of the early replicating portion of the interphase chromosome or to its length at metaphase. The number of dicentric chromosomes and centric rings per cell is limited primarily by the number of centromeres. These results are consistent with the assumption that every chromosome break is a site for chromosome-exchange.