Stable Chromosome Aberrations Research Articles

Conversion from the frequency of chromosome translocations in T-lymphocytes to the bone marrow dose in the long-term period after internal 89,90 Sr exposure

Cytogenetic Fluorescence In Situ Hybridization studies, that allow assessing the frequency of stable chromosome aberrations in circulating T lymphocytes, are commonly used in retrospective dosimetry in cases of uniform whole-body exposure. In the event of 89,90Sr exposure, interpretation of cytogenetic data is challenging, especially if blood sampling occurs long after the start of exposure. The weighted average dose to T-lymphocytes at the time of donor blood sampling in the long-term period after exposure to 89,90Sr does not coincide with the red bone marrow dose. Previously, we developed a model that allows us to estimate the weighted average doses to T-lymphocytes upon 89,90Sr ingress into the body of people belonging to various age groups. In this study, the modeling results were used to estimate the conversion factors from the frequency of translocations to the red bone marrow dose, which is important for assessing radiobiological effects associated with hematological diseases. The objective of our study is to estimate numerically the conversion factors (Brbm) from the dose to lymphocytes to the dose to red bone marrow for various scenarios of 89,90Sr ingestion depending on age, sex, and time after the start of exposure. The following scenarios are considered: single, uniform chronic for six months, uniform chronic for 1-5 years, non-uniform intake for 5 years (simulates the dynamics of intake in the Techa riverside settlements in 1950-1954). As a result, it has been found that the Brbm values significantly depend on the age at the time of 89,90Sr intake. The older the person is at the start of exposure, the more the cytogenetic dose differs (it is significantly lower) from the dose to the red bone marrow. We can say that the cytogenetic dose corresponds to the red bone marrow dose only in newborns and infants. This is due to the age-related dynamics of T-cell populations. Sex does not have a significant effect on Brbm. The effect of the 89,90Sr intake duration on Brbm is the most pronounced for 15-year-old adolescents. For them, the difference in Brbm values for a single and chronic 5-year ingress reaches 13%. Non-uniform intake of 90Sr over several years does not have a significant effect on Brbm and can be modelled by a uniform intake of the same duration.

Model of age-dependent dynamics and biokinetics of T-cells as natural biodosimeters.

Circulating T-lymphocytes are used as "natural biodosimeters" for estimating radiation doses, since the frequency of chromosomal aberrations induced in them is proportional to the accumulated dose. Moreover, stable chromosomal aberrations (translocations) are detected years and decades after exposure. Internal incorporation of radionuclides often leads to non-uniform exposure, which resulted in difficulties in the application of retrospective biodosimetry using T-lymphocytes. Some properties of T-lymphocytes complicate retrospective biodosimetry in this case: (1) the thymic production of T-cells depends significantly on age, the maximum is observed in early childhood; (2) the "lymphocyte-dosimeter" accumulates changes (translocations) while circulating through the body. The objective of this paper is to describe the technical characteristics of the model of age dynamics and T-cell biokinetics and approaches to assessing the dose to circulating lymphocytes under various exposure scenarios. The model allows to quantify the fractions of T-lymphocytes that were formed before and after exposure. The model takes into account the time fractions that circulating lymphocytes spend in various lymphoid organs. Age-related thymic involution was also considered. The model predicts that after internal exposure to 90Sr, the doses to T-lymphocytes can differ significantly from the doses to the bone marrow and other tissues. For uniform external γ-exposure, and for internal exposure due to non-bone -seeking radionuclides (for example, 144Ce), predicted doses to T-lymphocytes are very close to bone marrow doses. The model allows to quantify the correction factors for FISH-based doses to obtain doses to organs and tissues.

Contribution of radioactive particles to the post-explosion exposure of atomic bomb survivors implied from their stable chromosome aberration rates.

Even today when nearly 80 years have passed after the atomic bomb (A-bomb) was dropped, there are still debates about the exact doses received by the A-bomb survivors. While initial airborne kerma radiation (or energy spectrum of emitted radiation) can be measured with sufficient accuracy to assess the radiation dose to A-bomb survivors, it is not easy to accurately assess the neutron dose including appropriate weighting of neutron absorbed dose. Particularly, possible post-explosion exposure due to the radioactive particles generated through neutron activation have been almost neglected so far, mainly because of a large uncertainty associated to the behavior of those particles. However, it has been supposed that contribution of such non-initial radiation exposure from the neutron-induced radioactive particles could be significant, according to the findings that the stable chromosomal aberration rates which indicate average whole-body radiation doses were found to be more than 30% higher for those exposed indoors than for those outdoors even at the same initial dose estimated for the Life Span Study. In this Mini Review article, the authors explain that such apparently controversial observations can be reasonably explained by assuming a higher production rate of neutron-induced radioactive particles in the indoor environment near the hypocenter.

Preliminary study of chromosome aberrations using Giemsa, two-colour fish, and micronucleus assays in lymphocytes of individuals living in elevated radon concentration areas.

The frequencies of unstable and stable chromosome aberrations and micronuclei were examined in peripheral blood samples from 10 individuals living in elevated radon concentration areas (Takandeang Village, Mamuju, Indonesia). Blood samples from 10 people living in Topoyo Village were used as a control group. For unstable chromosome aberration analysis, a dicentric chromosome assay was conducted using conventional Giemsa staining. Chromosomal painting of chromosomes 1 and 4 using the fluorescence in situ hybridisation technique was also applied to four subjects to assess the stable chromosome aberration. Our study showed no significant increases across all groups in dicentric and other unstable chromosome aberrations, such as rings and acentric fragments. Translocations were found in one person from Takandeang Village and two Topoyo Village inhabitants. The translocations found in the subjects from Takandeang Village were due more to aging factors than to radon exposure. The number of micronuclei per 1000 binucleus cells in Takandeang Village inhabitants was not significantly different than that in the control group (p=0.943). A more comprehensive analysis should be conducted in a subsequent study by increasing the number of study donors and the number of metaphases to be analysed in both dicentric chromosome assay and fluorescence in situ hybridisation assays. Such research could provide valid information on the cytogenetic effects of elevated indoor radon exposure.

Detection of Primary DNA Lesions by Transient Changes in Mating Behavior in Yeast Saccharomyces cerevisiae Using the Alpha-Test.

Spontaneous or induced DNA lesions can result in stable gene mutations and chromosomal aberrations due to their inaccurate repair, ultimately resulting in phenotype changes. Some DNA lesions per se may interfere with transcription, leading to temporary phenocopies of mutations. The direct impact of primary DNA lesions on phenotype before their removal by repair is not well understood. To address this question, we used the alpha-test, which allows for detecting various genetic events leading to temporary or hereditary changes in mating type α→a in heterothallic strains of yeast Saccharomyces cerevisiae. Here, we compared yeast strains carrying mutations in DNA repair genes, mismatch repair (pms1), base excision repair (ogg1), and homologous recombination repair (rad52), as well as mutagens causing specific DNA lesions (UV light and camptothecin). We found that double-strand breaks and UV-induced lesions have a stronger effect on the phenotype than mismatches and 8-oxoguanine. Moreover, the loss of the entire chromosome III leads to an immediate mating type switch α→a and does not prevent hybridization. We also evaluated the ability of primary DNA lesions to persist through the cell cycle by assessing the frequency of UV-induced inherited and non-inherited genetic changes in asynchronous cultures of a wild-type (wt) strain and in a cdc28-4 mutant arrested in the G1 phase. Our findings suggest that the phenotypic manifestation of primary DNA lesions depends on their type and the stage of the cell cycle in which it occurred.

Cytogenetic Damage Induced by Radioiodine Therapy: A Follow-Up Case Study.

The risk of toxicity attributable to radioiodine therapy (RIT) remains a subject of ongoing research, with a whole-body dose of 2 Gy proposed as a safe limit. This article evaluates the RIT-induced cytogenetic damage in two rare differentiated thyroid cancer (DTC) cases, including the first follow-up study of a pediatric DTC patient. Chromosome damage in the patient's peripheral blood lymphocytes (PBL) was examined using conventional metaphase assay, painting of chromosomes 2, 4, and 12 (FISH), and multiplex fluorescence in situ hybridization (mFISH). Patient 1 (female, 1.6 y.o.) received four RIT courses over 1.1 years. Patient 2 (female, 49 y.o.) received 12 courses over 6.4 years, the last two of which were examined. Blood samples were collected before and 3-4 days after the treatment. Chromosome aberrations (CA) analyzed by conventional and FISH methods were converted to a whole-body dose accounting for the dose rate effect. The mFISH method showed an increase in total aberrant cell frequency following each RIT course, while cells carrying unstable aberrations predominated in the yield. The proportion of cells containing stable CA associated with long-term cytogenetic risk remained mostly unchanged during follow-up for both patients. A one-time administration of RIT was safe, as the threshold of 2 Gy for the whole-body dose was not exceeded. The risk of side effects projected from RIT-attributable cytogenetic damage was low, suggesting a good long-term prognosis. In rare cases, such as the ones reviewed in this study, individual planning based on cytogenetic biodosimetry is strongly recommended.

Effect of curcumin on γ-ray-induced cell response.

The purpose of the present study is to evaluate the effect of curcumin as a natural compound against radiation induced γ-foci and stable chromosome aberrations. Whole blood samples form three human volunteers were pretreated with curcumin at different concentrations (0.5, 10, 20 and 100μg/ml). After 1-hour incubation, the lymphocytes were exposed to γ-rays (0.05, 0.5, 1 and 2Gy). Radiation induced changes in cells were quantified using γ-H2AX/53BP1 assay and FISH analysis. Our results have shown that curcumin significantly reduced the frequency of both γ-foci and translocations. We found concentration-dependent increase of curcumin protective effect on γ-H2AX/53BP1 foci formation at all radiation doses. Concerning the translocations, after 0.05 and 0.5Gy γ-rays the values of genomic frequencies are comparable within each dose and we did not observe any impact of curcumin. The most protective effect after 1Gy exposure was found at 100μg/ml curcumin. At 2Gy irradiation, the maximum protection was achieved at 0.5 and 10μg/ml of curcumin. Concentrations of 20 and 100μg/ml also prevent lymphocytes but to less extent. Our in vitro study indicates radioprotective efficacy of curcumin against γ-ray induced damages in human lymphocytes. This observation suggests that curcumin may play a role to protect patients undergoing radiological procedures.

The Association of Radiation Exposure with Stable Chromosome Aberrations in Atomic Bomb Survivors Based on DS02R1 Dosimetry and FISH Methods.

The frequency of stable chromosome aberrations (sCA) in lymphocytes is a recognized radiation biological dosimeter. Its analysis can provide insights into factors that affect individual susceptibility as well as into the adequacy of radiation dose estimates used in studies of atomic bomb survivors. We analyzed the relationship between atomic bomb radiation exposure using the most recent DS02R1 dose estimates and the frequency of sCA as determined by FISH in 1,868 atomic bomb survivors. We investigated factors that may affect the background sCA rate and the shape and magnitude of the dose response. As in previous analyses of sCA in atomic bomb survivors that were based on Giemsa staining methods and used older DS86 dose estimates, the relationship between radiation dose and sCA rate was significant (P < 0.0001) with a linear-quadratic relationship at lower doses that did not persist at higher doses. As before, age at the time of the bombing and type of radiation shielding were significant dose-effect modifiers (P < 0.0001), but in contrast the difference in dose response by city was not so pronounced (P = 0.026) with a city effect not evident at doses below 1.25Gy. Background sCA rate increased with age at the time of examination (P < 0.0001), but neither sex, city, nor smoking was significantly associated with background rate. Based on FISH methods and recent dosimetry, the relationship between radiation dose and sCA frequency is largely consistent with previous findings, although the lesser importance of city as an effect modifier may reflect better dosimetry as well as more reproducible scoring of sCA. The persisting difference in sCA dose response by shielding category points to remaining problems with the accuracy or precision of radiation dose estimates in some A-bomb survivors.

Clinical, immunological and genetic research on the participants in mitigating the consequences of the Chernobyl nuclear accident

Introduction. The paper presents the results of research on the influence of IR sources on the health of professionally and accidentally exposed personnel. Particular emphasis is placed on: identifying the relationships between the level of radiation dose and the development of oncological diseases; use of contemporary biological dosimetry methods for retrospective analysis of irradiation doses; the impact of parental irradiation on the health of the offspring; the structure of morbidity, including oncological diseases in patients exposed to IR sources.&#x0D; Material and methods. The study material was used by subjects professionally and accidentally exposed to IR sources: medical staff and PMCCNA born in the Republic of Moldova, Ukraine and the Russian Federation, as well as their descendants, victims of the accident at the Fukushima Daiichi nuclear power plant (Japan) and residents of the region. Chelyabinsk. Clinical, immunological and cytogenetic methods were used.&#x0D; Results. A wide range of mental pathologies was observed at PMCCNA, at the victims of the accident at the Fukushima Daiichi nuclear power plant, etc. The structure of immune deficiency syndromes was dominated by allergic and autoimmune syndromes. Based on the analysis of stable chromosomal aberrations, exposure doses were established.&#x0D; Conclusions. In the absence of dose information received by staff professionally/accidentally exposed to IR sources, assessment of stable chromosomal aberrations makes it possible to reconstruct the radiation dose for PMCCNA exposed to low doses of IR.

Estimation of radiation doses on lymphocytes and their progenitors after ingestion of strontium-89,90

In radiobiology circulating T-lymphocytes are used as “natural biodosimeters” since the frequency of chromosomal aberrations that occur in them after radiation exposure is proportional to the accumulated dose. In addition, stable chromosomal aberrations (translocations) are detected in them years and decades after radiation exposure. Estimation of doses to circulating lymphocytes requires consideration of two dose components: the dose accumulated by the lymphocyte precursors (progenitors) in the red bone marrow; and dose accumulated by the lymphocytes in the lymphoid organs/tissues during circulation. A recently created model of T-lymphocyte exposure takes into account all these dose components, as well as the age-dependent dynamics of T-lymphocytes. The use of a model approach is especially important in assessing doses from osteotropic beta emitters (89,90Sr). They accumulate in the bone and locally expose predominately bone marrow. The dose to other lymphoid organs and tissues is much lower. The objective of this study is to evaluate the conversion factors from ingested 89,90Sr to the cumulative dose to circulating T-lymphocytes and their progenitors (DCL). For calculations, the previously developed model of T-lymphocyte exposure and new dose coefficients for the red bone marrow, estimated on the basis of a sex-and-age-dependent biokinetic model and a new dosimetric model of the human skeleton were used. As a result, the DCL values were evaluated for the first time. The age at the time of 89,90Sr intake varied from a newborn to 35 years, the age of T-lymphocyte examination (blood sampling age) was up to 75 years. The maximum values of DCL for both 90Sr and 89Sr were typical of children in the first years of life. It has been shown that doses to circulating T-lymphocytes from these radionuclides are lower than those to bone marrow, but are significantly higher than doses to other lymphoid tissues. The effect of sex on DCL is manifested for children 10 years of age and older. The area of DCL application covers the population of radioactively contaminated territories (the Urals region, the zone of the Chernobyl accident), as well as personnel of the nuclear industry enterprises.

Chromosome aberrations, micronucleus frequency, and catalase concentration in a population chronically exposed to high levels of radon

Purpose To deepen our knowledge on the effects of high levels of indoor radon exposure, we assessed the frequencies of unstable and stable chromosome aberrations and micronucleus (MN), as well as the concentration of an endogenous antioxidant (catalase, CAT), in blood samples of individuals chronically exposed to high indoor radon concentrations in Indonesia (Tande-Tande sub-village, Mamuju, West Sulawesi). Moreover, we also investigated the occurrence of a radio-adaptive response (RAR) in Tande-Tande sub-village inhabitants using the G2 MN assay. Materials and Methods The frequencies of dicentric (DC), acentric (AF), ring (R), and translocation (Tr) chromosomes in Tande-Tande inhabitants were compared to those in people living in a reference area with low levels of indoor radon levels (Topoyo village, Indonesia). The number of MN per 1000 binucleated cells (BNC) and CAT concentration per total protein was quantified and compared between groups. Lastly, we irradiated (2 Gy) phytohemagglutinin-stimulated samples in vitro and measured the frequency of MN to verify the occurrence of a RAR in Tande-Tande sub-village inhabitants. Results and Conclusion The frequencies of DC, AF, and Tr did not differ between Tande-Tande inhabitants and control subjects (p = 0.350, 0.521, 0.597). The frequency of MN in Tande-Tande inhabitants was significantly lower than that in the control group (p = 0.006). Similarly, CAT concentration in Tande-Tande inhabitants was also significantly lower than that in the control population (p < 0.001). Significant negative correlations were identified for MN number and CAT concentration versus indoor radon concentration, annual effective dose, or cumulative dose both within groups and when all data were analyzed together. Our findings indicate that, despite the high indoor radon levels, Tande-Tande inhabitants are not under oxidative stress, since this group had lower CAT concentration and MN frequency than those in the control group. The negative correlation between MN frequency and indoor radon concentration, annual effective dose, and cumulative dose suggests the occurrence of an RAR phenomenon in Tande-Tande sub-village inhabitants. This interpretation is also supported by the results of the G2 MN assay, which revealed lower MN frequencies after in vitro irradiation of samples from Tande-Tande sub-village inhabitants than those in samples from the control group (p = 0.0069, for cumulative MN frequency; p = 0.0146, for radiation-induced MN only).

Alternative end-joining originates stable chromosome aberrations induced by etoposide during targeted inhibition of DNA-PKcs in ATM-deficient tumor cells.

ATM and DNA-PKcs coordinate the DNA damage response at multiple levels following the exposure to chemotherapy. The Topoisomerase II poison etoposide (ETO) is an effective chemotherapeutic agent that induces DNA double-strand breaks (DSB), but it is responsible from the chromosomal rearrangements frequently found in therapy-related secondary tumors. Targeted inhibition of DNA-PKcs in ATM-defective tumors combined with radio- or chemotherapy has been proposed as relevant therapies. Here, we explored the DNA repair mechanisms and the genetic consequences of targeting the non-oncogenic addiction to DNA-PKcs of ATM-defective tumor cells after exposure to ETO. We demonstrated that chemical inhibition of DNA-PKcs followed by treatment with ETO resulted in the accumulation of chromatid breaks and decreased mitotic index in both A-T cells and ATM-knocked-down (ATMkd) tumor cells. The HR repair process in DNA-PKcs-inhibited ATMkd cells amplified the RAD51 foci number, with no correlated increase in sister chromatid exchanges. The analysis of post-mitotic DNA lesions presented an augmented number of persistent unresolved DSB, without alterations in the cell cycle progression. Long-term examination of chromosome aberrations revealed a strikingly high number of chromatid and chromosome exchanges. By using genetic and pharmacological abrogation of PARP-1, we demonstrated that alternative end-joining (alt-EJ) repair pathway is responsible for those chromosome abnormalities generated by limiting c-NHEJ activities during directed inhibition of DNA-PKcs in ATM-deficient cells. Targeting the non-oncogenic addiction to DNA-PKcs of ATM-defective tumors stimulates the DSB repair by alt-EJ, which is liable for the origin of cells carrying stable chromosome aberrations that may eventually restrict the therapeutic strategy.

Analysis of Short-Term and Stable DNA Damage in Patients with Differentiated Thyroid Cancer Treated with 131I in Hypothyroidism or with Recombinant Human Thyroid-Stimulating Hormone for Remnant Ablation.

It is well known that ionizing radiation can induce genetic damage and that oxidative stress is a major factor inducing it. Our aim was to investigate whether thyroid remnant ablation with low activities of 131I (1,850 MBq) is associated with DNA damage by evaluating the CometAssay, micronuclei, and chromosome aberrations with multicolor fluorescent in situ hybridization. Methods: We studied 62 patients prepared with recombinant human thyroid-stimulating hormone (rhTSH) or by thyroid hormone withdrawal. In both groups, we analyzed stable and unstable genetic alterations before 131I therapy and 1 wk and 3 mo after 131I administration. We also correlated the genetic damage with several variables, including the degree of radiation-induced oxidative stress, genetic polymorphisms of enzymes involved in DNA repair, and antioxidative stress. Results: We found a comparable amount of DNA breaks evaluated by CometAssay and micronuclei testing in both groups of patients at different time points, but there was a significant increase in stable chromosome aberrations evaluated by multicolor fluorescent in situ hybridization (breaks and translocations) in patients prepared with thyroid hormone withdrawal. Overall, high chromosome damage was associated with higher retained body radioactivity and unfavorable gene polymorphism. A high level of free oxygen radicals and a low level of antioxidants were found in all patients at any time point. In particular, patients prepared with thyroid hormone withdrawal, at 3 mo, had significantly higher levels of free oxygen radicals than those prepared with rhTSH. Conclusion: An increase in stable chromosome aberrations with respect to baseline is detectable after administration of low doses of 131I in patients prepared with thyroid hormone withdrawal but not in patients prepared with rhTSH. The clinical significance of these chromosomal alterations remains to be determined.

Cytogenetic follow-up studies on humans with internal and external exposure to ionizing radiation

Cells exposed to ionizing radiation have a wide spectrum of DNA lesions that include DNA single-strand breaks, DNA double-strand breaks (DSBs), oxidative base damage and DNA-protein crosslinks. Among them, DSB is the most critical lesion, which when mis-repaired leads to unstable and stable chromosome aberrations. Currently, chromosome aberration analysis is the preferred method for biological monitoring of radiation-exposed humans. Stable chromosome aberrations, such as inversions and balanced translocations, persist in the peripheral blood lymphocytes of radiation-exposed humans for several years and, therefore, are potentially useful tools to prognosticate the health risks of radiation exposure, particularly in the hematopoietic system. In this review, we summarize the cytogenetic follow-up studies performed by REAC/TS (Radiation Emergency Assistance Center/Training site, Oak Ridge, USA) on humans exposed to internal and external radiation. In the light of our observations as well as the data existing in the literature, this review attempts to highlight the importance of follow-up studies for predicting the extent of genomic instability and its impact on delayed health risks in radiation-exposed victims.

Retrospective cytogenetic analysis of unstable and stable chromosome aberrations in the victims of radiation accident in Bulgaria

Five occupational workers in an industrial sterilization unit at Stamboliyski in Bulgaria were accidentally exposed to a very high specific activity of Cobalt-60 source on June 14, 2011. Initial cytogenetic analysis performed on days 2 and 7 after radiation exposure revealed the whole body absorbed radiation doses of 5.32 Gy for patient 1, 3.40 Gy for patient 2, 2.50 Gy for patient 3, 1.91 Gy for patient 4 and 1.24 Gy for patient 5 [1]. Here, a retrospective multicolor FISH analysis was performed on three patients (patients 1, 2 and 3) using the blood samples collected over a period of 4 years from 2012 through 2015. In all the three patients, cells with stable chromosome aberrations (simple and complex chromosome translocations) were 3–4 folds more than cells with unstable chromosome aberrations (dicentric, rings and excess acentric chromosome fragments). In corroboration with the results reported in the literature, we observed that the time dependent decline of dicentrics, rings and excess acentric fragments occurred much more rapidly than chromosome translocations in the blood samples of the three victims. Further, inter-individual variation in the decline of radiation induced chromosome aberrations was also noticed among the three victims. The reason for the increased persistence of balanced chromosome translocations is not entirely clear but may be attributed to certain subsets of long-lived T-lymphocytes. The retrospective cytogenetic follow up studies on radiation-exposed victims may be useful for determining the extent of genomic/chromosomal instability in the hematopoietic system.

Rogue cell-like chromosomal aberrations in peripheral blood lymphocytes of interventional radiologists: A case study

We report two cases of interventional radiologists who had been exposed to radiation while performing fluoroscopically-guided interventional procedures (FGIPs), mainly transcatheter arterial chemoembolization, percutaneous catheter drainage, and percutaneous transhepatic biliary drainage procedures, for over 10 years. They had a unique multi-aberrant cell type with not only high numbers of dicentrics and/or centric rings but also excess acentric double minutes, similar to a rogue cell. As revealed in a self-administered questionnaire, they wore personal dosimeters and protective equipment at all times and used shielding devices during interventional fluoroscopy procedures. However, the exposed dose levels derived from cytogenetic dosimetry were much higher than the doses recorded on their personal dosimeters. A large number of unstable and stable chromosomal aberrations that were found in the peripheral blood lymphocytes of these interventional radiologists might be due to repeated and long-term exposure to ionizing radiation while performing FGIPs. Further investigations of chromosomal aberrations in interventional radiologists may improve the understanding of the long-term effects of radiation exposure on medical personnel.

THE ABILITY OF CYTOGENETIC ANALYSIS TO ESTIMATE RADIATION DOSES RETROSPECTIVELY IN CHERNOBYL ACCIDENT RECOVERY WORKER

Relevance. There is a need to evaluate doses retrospectively in Chernobyl nuclear power plant accident recovery workers without established external doses.Intention: To assess the ability of cytogenetic analysis to estimate external radiation doses retrospectively in Chernobyl nuclear power plant accident recovery workers exposed to low-dose radiation in the remote period.Methodology. Cytogenetic biological indication and biological dosimetry were performed in Chernobyl nuclear power plant accident recovery workers 27–30 years after their participation in recovery works. Stable and unstable chromosome aberrations were assessed in peripheral blood lymphocytes.Results and Discussion. The analysis of unstable chromosome aberrations showed that 45.1 % of Chernobyl nuclear power plant accident recovery workers had radiation markers more frequently than in the comparison group. Biological doses were retrospectively evaluated in 18 % of Chernobyl nuclear power plant accident recovery workers and ranged within 14–48 cGy. Specific anamnestic factors should be assessed while evaluating doses retrospectively.Conclusion. Analysis of stable chromosome aberrations allows retrospective dosimetry after low-dose exp sure if external dose is unavailable. Based on this, adverse health effects of low-dose exposure can be assessed and reimbursed in Chernobyl nuclear power plant accident recovery workers.

Detection of Simple, Complex, and Clonal Chromosome Translocations Induced by Internal Radioiodine Exposure: A Cytogenetic Follow-Up Case Study after 25 Years

Here, we report the findings of a 25-year cytogenetic follow-up study on a male patient who received 2 rounds of radioiodine treatment within a span of 26 months (1.78 GBq in 1992 and 14.5 GBq in 1994). The patient was 34 years old with a body mass index of 25 at the time of the first radioiodine treatment. Multicolor FISH and multicolor banding (mBAND) techniques performed on the patient detected inter- and intrachromosomal exchanges. Although the frequency of chromosome translocations remained essentially the same as reported in our earlier study (0.09/cell), the percentage of reciprocal (balanced) translocations increased from 54.38 to 80.30% in the current study. In addition to simple chromosome translocations, complex exchanges (0.29%) involving more than 2 chromosomes were detected for the first time in this patient. Strikingly, a clonal translocation involving chromosomes 14 and 15, t(14p;15q), was found in 7 of the 677 cells examined (1.03%). The presence of complex and clonal translocations indicates the onset of chromosomal instability induced by internal radioiodine exposure. mBAND analysis using probes specific for chromosomes 1, 2, 4, 5, and 10 revealed 5 inversions in a total of 717 cells (0.69%), and this inversion frequency is several-fold higher than the baseline frequency reported in healthy individuals using the classical G-banding technique. Collectively, our study suggests that stable chromosome aberrations such as translocations and inversions can be useful not only for retrospective biodosimetry but also for long-term monitoring of chromosomal instability caused by past radioiodine exposure.

Interpretation of FISH Results in the Case of Nonuniform Internal Radiation Exposure of Human Body with the Use of Model Approach

The fluorescence in situ hybridization (FISH) technique allows for the estimation of the number of stable chromosomal aberrations (translocations) in human blood T-lymphocytes decades after radiation exposure. Therefore, it is used for retrospective assessment of irradiation doses received by red bone marrow (RBM). Cytogenetic analysis of individuals exposed on the Techa River in the 1950s to 89,90Sr, locally irradiating RBM, showed that dose assessment based on FISH data led to underestimation of the actual dose estimated from measurements of whole-body 90Sr content. The purpose of current study was to evaluate the dose–effect relationship and the frequency of translocations per 1 Gy of RBM irradiation dose and T-lymphocytes dose for donors living in Techa riverside villages (n = 178; translocation yield = 2389; number of genome equivalents GE = 96 446). Irradiation doses were estimated using the latest version of the Techa River dosimetry system and the T-cell irradiation model. Statistical analysis showed that the frequency of translocations per 1000 GE per 1 Gy of RBM dose was 8.0 ± 0.7; this value was statistically significantly lower than the value estimated for Sellafield radiation workers under external exposure (11.6 ± 1.6). At the same time, the use of T-cell and their progenitor doses led to re-evaluation (increase) in the slope of the dose–response curve to 11.8 ± 1.6 per 1 Gy per 1000 GE, which agreed well with the published data. The obtained estimates of the background frequencies of translocations also were close to the published values ​​for unexposed donors. These findings demonstrate the legitimacy of using a model approach for estimation of irradiation doses in T-lymphocytes and their progenitors and the need to take into account complex T-cell dynamics in interpretation of cytogenetic data for the purposes of biodosimetry.

Use of human lymphocyte G0 PCCs to detect intra- and inter-chromosomal aberrations for early radiation biodosimetry and retrospective assessment of radiation-induced effects.

A sensitive biodosimetry tool is required for rapid individualized dose estimation and risk assessment in the case of radiological or nuclear mass casualty scenarios to prioritize exposed humans for immediate medical countermeasures to reduce radiation related injuries or morbidity risks. Unlike the conventional Dicentric Chromosome Assay (DCA), which takes about 3–4 days for radiation dose estimation, cell fusion mediated Premature Chromosome Condensation (PCC) technique in G0 lymphocytes can be rapidly performed for radiation dose assessment within 6–8 hrs of sample receipt by alleviating the need for ex vivo lymphocyte proliferation for 48 hrs. Despite this advantage, the PCC technique has not yet been fully exploited for radiation biodosimetry. Realizing the advantage of G0 PCC technique that can be instantaneously applied to unstimulated lymphocytes, we evaluated the utility of G0 PCC technique in detecting ionizing radiation (IR) induced stable and unstable chromosomal aberrations for biodosimetry purposes. Our study demonstrates that PCC coupled with mFISH and mBAND techniques can efficiently detect both numerical and structural chromosome aberrations at the intra- and inter-chromosomal levels in unstimulated T- and B-lymphocytes. Collectively, we demonstrate that the G0 PCC technique has the potential for development as a biodosimetry tool for detecting unstable chromosome aberrations (chromosome fragments and dicentric chromosomes) for early radiation dose estimation and stable chromosome exchange events (translocations) for retrospective monitoring of individualized health risks in unstimulated lymphocytes.