Chromosome Aberrations In Lymphocytes Research Articles

Influencing factors of occupational health of clinical nuclear medical staff

Objective: To analyze the characteristics and its influencing factors of occupational injury among clinical nuclear medicine staff, and to put forward suggestions for formulating relevant radiation protection intervention measures. Methods: In March 2022, a study was conducted involving 12 medical institutions engaged in nuclear medicine in Gansu Province. The occupational health examination data of 1451 clinical nuclear medicine staff were analyzed. The study subjects were divided into two groups based on the median annual effective dose of external exposure in 2022: Group A (annual effective dose ≤0.2 mSv, n=927) and group B (annual effective dose >0.2 mSv, n=524). The effects of annual effective dose, age, seniority, gender and occupational category on occupational health of clinical nuclear medicine staff were analyzed. Classification variables between groups were compared with Pearson χ(2) test. Multivariate logistic regression was used to analyze the influencing factors of the abnormal results. Results: The abnormal rates of white blood cell count (WBC), red blood cell count (RBC) and hemoglobin (HGB) in female clinical nuclear medical staff were higher than those in males, and the differences were statistically significant (P<0.001). The abnormal rates of WBC and HGB in clinical nuclear medicine staff of different occupational categories were statistically significant (P<0.05). The abnormal rates of RBC and HGB of clinical nuclear medicine staff in annual effective dose group B were higher than those in group A, and the differences were statistically significant (P<0.05). Multivariate logistic regression results showed that the abnormal risks of RBC in annual effective dose group B was 2.465 times of that in group A, the abnormal risks of RBC, WBC and HGB in females were 9.354, 2.939 and 6.760 times of those in males, respectively. The abnormal risk of WBC in the radiotherapy group was 2.334 times of that in general radiotherapy group. The abnormal risk of lens in nuclear medicine group was 2.459 times of that in general radiotherapy group. The abnormal risk of ECG and lens in ≥35 years old age group were 1.814 times and 1.969 times of those in <35 years old age group, respectively. The abnormal risk of lens of the ≥10 working years group was 1.899 times of that in the <10 working years group. The risk of lymphocyte micronucleus abnormality in the interventional group was 1.481 times of that in the general radiotherapy group, the risk of lymphocyte micronucleus abnormality in females was 2.215 times of that in males. The risk of lymphocyte micronucleus abnormality and lymphocyte chromosome aberration in ≥35 years old age group were 2.552 and 2.266 times of those in <35 years old age group, respectively. The risk of lymphocyte micronucleus abnormality in the group with≥10 working years was 1.443 times of that in<10 working years group (P<0.05) . Conclusion: Long-term low-dose ionizing radiation has a certain effect on the lens and genetic indexes of clinical nuclear medicine staff.

Oral subchronic toxicity study and genetic toxicity evaluation of mitoquinone mesylate

AbstractMitochondrial dysfunction and excessive reactive oxygen species production contributes to the pathophysiology of aging. Coenzyme Q10 is thought to protect mitochondria from oxidative damage; thus, mitoquinone was developed as mitochondria‐targeted analogue with similar antioxidant activity. Mitoquinone is the oxidized form of mitoquinol. Mitoquinone/mitoquinol mesylate has been proposed as a food ingredient. As part of the safety analysis, we performed genotoxicity assays and a 39‐week toxicity study to determine overall toxicity potential. Mitoquinone mesylate showed no evidence of genotoxic potential in two in vitro assays, bacterial reverse mutation and human lymphocyte chromosome aberration, nor in the in vivo micronucleus test in rats. In the 39‐week study in dogs, there were no findings observed, which were considered to represent adverse systemic toxicity; therefore, the high dose level (40 mg/kg/day) was considered the NOAEL. The principal findings in this study were fecal disturbances and vomiting. These findings were considered to be due to a local, possibly irritant effect of the test substance on the gastrointestinal tract and were not considered adverse as there were no impacts on clinical or histopathology. This highest dose exceeds the expected daily human intake more than 100‐fold. Data from well‐designed clinical trials actively collecting safety endpoints corroborate that 20 mg/day can be safely consumed and is not likely to result in significant gastrointestinal complaints. These results support the conclusion that the use of mitoquinone/mitoquinol mesylate as a food ingredient is safe.

Analysis of chromosome aberrations in peripheral blood lymphocyte of medical radiation workers in a tertiary hospital

Objective: To analyze the level of chromosome aberration in lymphocytes of medical radiation workers and its influencing factors. Methods: From July to September 2020, 252 medical workers in a tertiary hospital were selected as the study subjects and 107 preserviceworkers were selected as the control group. The Chromosomal aberrations of peripheral blood lymphocytes were measured using conventional cytogenetic analysis method, and the differences were analyzed. Results: The frequencies of dicentric puls centric ring, total chromosome-type aberrations, and abnormal detection rate in the radiation group were significantly higher than those in the control group (Z=2.59, 3.74, 9.99, P<0.05). There was significant difference in the frequencies of dicentric plus centric ring and total chromosome-type aberrations among different types of work (χ(2)=8.59, 8.17, 11.39, P<0.05), and the frequencies of dicentric plus centric ring were significantly higher in the interventional radiology group than those in diagnostic radiology (χ(2)=2.90, P<0.05), While the rates of acentric fragment and total chromosome-type aberrations were significantly higher in the nuclear medicine group than those in diagnostic radiology (χ(2)=2.81, 3.19, P<0.05). The difference in the abnormal detection rate of chromosome aberrations between different types of work was statistically significant (P<0.05), and the rate in the interventional radiology group was significantly higher than that in the diagnostic radiology group (χ(2)=7.66, P<0.05). There was no significant difference in chromosome aberration level and abnormal detection rate among different working ages (P>0.05). Poisson regression analysis indicated that the type of work is a risk factor for chromosomal aberration [IRR=2.31 (nuclear medicine group), 1.66 (Radiation therapy), and 1.78 (interventional group) ; P<0.05]. Conclusion: Ionizing radiation causes certain radiation damage to medical radiology workers, and the frequencies of chromosome aberration in the radiation workers of nuclear medicine and interventional radiology groups are relatively high, so radiation protection should be strengthened to ensure the health of relevant workers.

Chromosome damage in regions with different levels of air pollution.

Air pollution is an important environmental factor influencing human health. In this study, we compared chromosome damage in city policemen from three cities in the Czech Republic: industrial Ostrava characterized by high levels of benzo[a]pyrene, Prague with heavy traffic emitting nitrogen oxides, and relatively clean Ceske Budejovice located in an area with predominantly agricultural activity. Chromosomal aberrations in lymphocytes were evaluated by fluorescence in situ hybridization with painting probes for chromosomes 1, 2, 3, and 4 in spring and autumn. An increase in the frequency of unstable chromosome aberrations, that is, dicentric chromosomes and acentric fragments, was observed in spring samples from Ostrava (p = .014 and p = .044, respectively) and Prague (p = .002 and p = .006, respectively) in comparison with Ceske Budejovice. The difference was significant only for samples taken after the winter period, when the concentration of pollutants in the air increases due to poor dispersion conditions. An increased frequency of dicentric chromosomes was observed in spring compared to autumn in both Ostrava and Prague (p = .017 and p = .023, respectively), but not in Ceske Budejovice. More breakpoints were observed on chromosome 1 than on the other chromosomes examined (p < .001). The number of breakpoints in the heterochromatin region 1p11-q12 was lower than in other parts of chromosome 1 (p < .001), suggesting a protective function of heterochromatin against damage. Our study showed, that air pollution increased the frequency of unstable chromosome aberrations, especially dicentric chromosomes. However, we did not show an effect on stable chromosome rearrangements.

Exploring X Chromosomal Aberrations in Ovarian Cells by using Fluorescence In Situ Hybridization.

Millions of people worldwide deal with issues concerning fertility. Reduced fertility, or even infertility, may be due to many different causes, including genetic disorders, of which chromosomal abnormalities are the most common. Fluorescence in situ hybridization (FISH) is a well-known and frequently used method to detect chromosomal aberrations in humans. FISH is mainly used for the analysis of chromosomal abnormalities in the spermatozoa of males with numerical or structural chromosomal aberrations. Furthermore, this technique is also frequently applied in females to detect X chromosomal aberrations that are known to cause ovarian dysgenesis. However, information on the X chromosomal content of ovarian cells from females with X chromosomal aberrations in lymphocytes and/or buccal cells is still lacking. The aim of this study is to advance basic research regarding X chromosomal aberrations in females, by presenting two methods based on FISH to identify the X chromosomal content of ovarian cells. First, a method is described to determine the X chromosomal content of isolated ovarian cells (oocytes, granulosa cells, and stromal cells) in non-grafted ovarian cortex tissue from females with X chromosomal aberrations. The second method is directed at evaluating the effect of chromosomal aberrations on folliculogenesis by determining the X chromosomal content of ovarian cells of newly formed secondary and antral follicles in ovarian tissue, from females with X chromosomal aberrations after long-term grafting into immunocompromised mice. Both methods could be helpful in future research to gain insight into the reproductive potential of females with X chromosomal aberrations.

Cytogenetic features in adolescent girls with abnormal uterine bleeding which is comorbid with multi­factor diseases

Objective — to study the state of chromosomal apparatus in adolescent girls with abnormal uterine bleeding which is comorbid with multi-­factor diseases.&#x0D; Materials and methods. Cytogenetic analysis has been carried out in 25 girls aged 14 to 17 with abnormal uterine bleeding (AUB) which is comorbid with multifactor diseases (endocrine and nervous). The comparison group included 25 age-matching healthy girls. All the girls have been examined in the Laboratory of Medical Genetics of the Institute. Statistical processing of the study results has been carried out following the Student’s t­test with the use of Excel software package.&#x0D; Results and discussion. According to the data of cytogenetic analysis, it has been established that the total level of chromosome aberrations in blood lymphocytes of sick girls constituted 5.44 % and exceeded this value by a factor of 2.2 in comparison with the frequency in healthy girls. A 1.8-­fold increase of the number of chromosome aberrations was observed; among them the paired acentric fragments have been recorded twice as often. Chromatid­type aberrations in blood lymphocytes were observed in 2.9 times oftener in girls with AUB, mainly due to an increase in the number of single acentric fragments. The frequency of genomic disorders was 0.60 % that is five times more than their frequency in blood lymphocytes of healthy girls.&#x0D; Conclusions. Cytogenetic analysis conducted in adolescent girls with abnormal uterine bleeding and comorbid pathology have revealed an increase of the overall level of chromosome aberrations in comparison with healthy girls. Paired acentric fragments prevailed among chromosome aberrations, single acentric fragments prevailed among chromatid-­type aberrations, polyploid cells prevailed among genomic disorders.

High Resolution and Automatable Cytogenetic Biodosimetry Using In Situ Telomere and Centromere Hybridization for the Accurate Detection of DNA Damage: An Overview.

In the event of a radiological or nuclear accident, or when physical dosimetry is not available, the scoring of radiation-induced chromosomal aberrations in lymphocytes constitutes an essential tool for the estimation of the absorbed dose of the exposed individual and for effective triage. Cytogenetic biodosimetry employs different cytogenetic assays including the scoring of dicentrics, micronuclei, and translocations as well as analyses of induced premature chromosome condensation to define the frequency of chromosome aberrations. However, inherent challenges using these techniques include the considerable time span from sampling to result, the sensitivity and specificity of the various techniques, and the requirement of highly skilled personnel. Thus, techniques that obviate these challenges are needed. The introduction of telomere and centromere (TC) staining have successfully met these challenges and, in addition, greatly improved the efficiency of cytogenetic biodosimetry through the development of automated approaches, thus reducing the need for specialized personnel. Here, we review the role of the various cytogenetic dosimeters and their recent improvements in the management of populations exposed to genotoxic agents such as ionizing radiation. Finally, we discuss the emerging potentials to exploit these techniques in a wider spectrum of medical and biological applications, e.g., in cancer biology to identify prognostic biomarkers for the optimal triage and treatment of patients.

Dose-Dependent Transmissibility of Chromosome Aberrations in Human Lymphocytes at First Mitosis. II. Biological Effectiveness of Heavy Charged Particles Versus Gamma Rays.

Chromosome aberrations (CAs) are large scale structural rearrangements to the genome that have been used as a proxy endpoint of mutagenic and carcinogenic potential. And yet, many types of CAs are incapable of causing either of these effects simply because they are lethal. Using 24-color multi-fluor combinatorial painting (mFISH), we examined CAs in normal human lymphocytes exposed to graded doses of 1 GeV/nucleon accelerated 56Fe ions and 662 keV 137Cs gamma rays. As expected, the high-linear energy transfer (LET) heavy ions were considerably more potent per unit dose at producing total yields of CAs compared to low-LET gamma rays. As also anticipated, the frequency distribution of aberrations per cell exposed to 56Fe ions was significantly overdispersed compared to the Poisson distribution, containing excess numbers of cells devoid of aberrations. We used the zero-inflated negative binomial (ZINB) distribution to model these data. Based on objective cytogenetic criteria that are subject to caveats we discuss, each cell was individually evaluated in terms of likely survival (i.e., its ability to transmit to daughter cell progeny). For 56Fe ion irradiations, the frequency of surviving cells harboring complex aberrations represented a significant portion of aberration-bearing cells, while for gamma irradiation no survivable cells containing complex aberrations were observed. When the dose responses for the two radiation types were compared, and the analysis was limited to surviving cells that contained aberrations, we were surprised to find the high-LET 56Fe ions only marginally more potent than the low-LET gamma rays for doses less than 1 Gy. In fact, based on dose-response modeling, they were predicted to be less effective than gamma rays at somewhat higher doses. The major implication of these findings is that measures of relative biological effectiveness that fail to account for coincident lethality will tend to overstate the impact of transmissible chromosomal damage from high-LET particle exposure.

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.

The effect of arsenic, cadmium, mercury, and lead on the genotoxic activity of Boletaceae family mushrooms present in Serbia

ABSTRACT The aim of this study was to determine accumulation of heavy metals and metalloids which are widely distributed in the environment and in food chain using wild edible mushrooms belonging to the Boletaceae family mushrooms. In addition, methanol extracts of mushrooms were tested for in vitro protective effect by the cytochalasin-B blocked micronucleus (CBMN) assay using chromosome aberrations in human peripheral lymphocytes as a model. The genotoxic activity of methanol extracts prepared at 4 different concentrations (1, 2, 3 or 6 µg/ml) was examined using amifostine and mitomycin C as positive controls. Extracts of species B. regius and B. edulis exhibited the greatest reduction in the frequency of micronuclei (MN). Extract of B. regius at concentrations of 2 µg/ml showed the highest decrease in number of MN. In comparison, extract of mushroom B. edulis at a concentration of 3 µg/ml displayed less reduction. However, as heavy metals and metalloids are found in mushrooms, another aim was to examine whether these agents affected genotoxicity. Principal component analysis (PCA) identified clustering differences between control and heavy metals and metalloids groups and might explain the influence of heavy element content and genotoxic activity in mushrooms.

Beyond Traditional Use of Alchemilla vulgaris: Genoprotective and Antitumor Activity In Vitro

Alchemilla vulgaris L. (lady's mantle) was used for centuries in Europe and Balkan countries for treatments of numerous conditions and diseases of the reproductive system, yet some of the biological activities of lady's mantle have been poorly studied and neglected. The present study aimed to estimate the potential of A. vulgaris ethanolic extract from Southeast Serbia to prevent and suppress tumor development in vitro, validated by antioxidant, genoprotective, and cytotoxic properties. A total of 45 compounds were detected by UHPLC-HRMS analysis in A. vulgaris ethanolic extract. Measurement of antioxidant activity revealed the significant potential of the tested extract to scavenge free radicals. In addition, the analysis of micronuclei showed an in vitro protective effect on chromosome aberrations in peripheral human lymphocytes. A. vulgaris extract strongly suppressed the growth of human cell lines derived from different types of tumors (MCF-7, A375, A549, and HCT116). The observed antitumor effect is realized through the blockade of cell division, caspase-dependent apoptosis, and autophagic cell death. Our study has shown that Alchemilla vulgaris L. is a valuable source of bioactive compounds able to protect the subcellular structure from damage, thus preventing tumorigenesis as well as suppressing tumor cell growth.

Spontaneous Chromosomal Aberrations in Lymphocytes and Development of Tumor in Hospital Workers.

Cytogenetic analysis of chromosomes in blood lymphocytes can be used to reveal biomarkers of tumor risk. The frequency of chromosomal aberrations (CAs) appears to correlate with the later incidence of cancer. In our work, a total of 515 healthy Hungarian medical workers and 725 controls were enrolled in our investigation. The CAs in peripheral blood lymphocytes were analyzed. The frequency of CAs was significantly higher in the groups working with ionizing radiation and with cytostatic agents compared to unexposed controls and in male smokers rather than non-smokers. The frequency of dicentric chromosomes, however, was not significantly different between control and exposed groups. Among 82 cancer cases (6.6%), the most frequent types were cancer of the breast (20.5%), colon (12.8%), lung and thyroid gland (9-9%). Our analysis showed 8.1% cancer cases in smokers compared to 5.7% in non-smokers. The potential exposure to carcinogens did not modify the effect of CAs on cancer risk but tobacco smoking did increase risk.

A multi-detector experimental setup for the study of space radiation shielding materials: Measurement of secondary radiation behind thick shielding and assessment of its radiobiological effect

Space agencies have recognized the risks of astronauts’ exposure to space radiation and are developing complex model-based risk mitigation strategies. In the foundation of these models, there are still significant gaps of knowledge concerning nuclear fragmentation reactions which need to be addressed by ground-based experiments. There is a lack of data on neutron and light ion production by heavy ions, which are an important component of galactic cosmic radiation (GCR). A research collaboration has been set up to characterize the secondary radiation field produced by GCR-like radiation provided by a particle accelerator in thick shielding. The aim is to develop a novel method for producing high-quality experimental data on neutron and light ion production in shielding materials relevant for space radiation protection. Four complementary detector systems are used to determine the energy and angular distributions of high-energy secondary neutrons and light ions. In addition to the physical measurement approach, the biological effectiveness of the secondary radiation field is determined by measuring chromosome aberrations in human peripheral lymphocytes placed behind the shielding. The experiments are performed at the heavy ion

Dose estimation after a mixed field exposure: Radium-223 and intensity modulated radiotherapy

IntroductionRadium-223 dichloride ([223Ra]RaCl2), a radiopharmaceutical that delivers α-particles to regions of bone metastatic disease, has been proven to improve overall survival of men with metastatic castration resistant prostate cancer (mCRPC). mCRPC patients enrolled on the ADRRAD clinical trial are treated with a mixed field exposure comprising radium-223 (223Ra) and intensity modulated radiotherapy (IMRT). While absorbed dose estimation is an important step in the characterisation of wider systemic radiation risks in nuclear medicine, uncertainties remain for novel radiopharmaceuticals such as 223Ra. Methods24-Colour karyotyping was used to quantify the spectrum of chromosome aberrations in peripheral blood lymphocytes of ADRRAD patients at incremental times during their treatment. Dicentric equivalent frequencies were used in standard models for estimation of absorbed blood dose. To account for the mixed field nature of the treatment, existing models were used to determine the ratio of the component radiation types. Additionally, a new approach (M-FISHLET), based on the ratio of cells containing damage consistent with high-LET exposure (complex chromosomal exchanges) and low-LET exposure (simple exchanges), was used as a pseudo ratio for 223Ra:IMRT dose. ResultsTotal IMRT estimated doses delivered to the blood after completion of mixed radiotherapy (after 37 IMRT fractions and two [223Ra]RaCl2 injections) were in the range of 1.167 ± 0.092 and 2.148 ± 0.096 Gy (dose range across all models applied). By the last treatment cycle analysed in this study (four [223Ra]RaCl2 injections), the total absorbed 223Ra dose to the blood was estimated to be between 0.024 ± 0.027 and 0.665 ± 0.080 Gy, depending on the model used. Differences between the models were observed, with the observed dose variance coming from inter-model as opposed to inter-patient differences. The M-FISHLET model potentially overestimates the 223Ra absorbed blood dose by accounting for further PBL exposure in the vicinity of metastatic sites. ConclusionsThe models presented provide initial estimations of cumulative dose received during incremental IMRT fractions and [223Ra]RaCl2 injections, which will enable improved understanding of the doses received by individual patients. While the M-FISHLET method builds on a well-established technique for external exposures, further consideration is needed to evaluate this method and its use in assessing non-targeted exposure by 223Ra after its localization at bone metastatic sites.

Flavonoids of the Heartwood of Cotinus coggygria Scop. Showing Protective Effect on Human Lymphocyte DNA

In continuation of our study on Cotinus coggygria from Serbia, 10 known flavonoids (1-10) were isolated from the methylene chloride/methanol extract of the heartwood. They were tested for in vitro protective effect against chromosome aberrations in peripheral human lymphocytes, using the cytokinesis-block micronucleus assay. All tested compounds (in minimal doses of 1 μg/mL) exerted a beneficial effect by decreasing DNA damage of human lymphocytes in the range of 24.2% to 54.5%, better than the radio protectant control, amifostine. Functional groups, such as 3′,4′-dihydroxyphenyl (catechol), 5-OH, 3-OH, and 4-keto in flavonoids (3-keto in aurones), which play a key role in antioxidant activity, are proposed to be responsible for the DNA protective activity of the tested compounds.

Analysis on the status of occupational health of medical radiation workers in China in 2019

Objective: To grasp the occupational health monitoring of radiation workers in medical institutions across the country, and to discover weak links in the prevention and treatment of occupational radiation diseases. Methods: In 2020 January, according to the monitoring data of the "National Radiation Health Information Platform" (Occupational Radiation Disease and Occupational Health Monitoring Subsystem and Occupational Radiation Disease Reporting Subsystem) , the national occupational health monitoring data from January 1 to December 31, 2019, including the number of radiation workers in medical institutions, occupational health examinations, personal dose monitoring and occupational radiation disease diagnosis, were descriptive analyzed. Results: There were a total of 394436 radiation workers in medical institutions across the country. The number of radiation workers in various provinces was quite different, with a median of 10206, which was positively correlated with the number of permanent residents in each province (r=0.947) . There were 376 personal dose monitoring institutions nationwide, and the personal dose monitoring rate of radiation workers in medical institutions was 96.61% (381045/394436) . There were 419 occupational health inspection institutions for radiation workers across the country, and 269 (64.20%) used software to print physical examination forms. A total of 334455 radiation workers in medical institutions had been subjected to occupational health examinations. The rate of occupational health examinations for radiation workers in medical institutions was 84.79% (334455/394436) . The abnormal rate of chromosomal aberrations in peripheral blood lymphocytes of radiation workers in medical institutions was 0.33% (776/233571) , the detection rate of posterior posterior subcapsular turbidity was 0.63% (2093/334455) , and the abnormality rate of thyroid color ultrasound was 28.49% (14946/52464) . In 2019, a total of 16 cases of occupational radiation diseases were reported. Conclusion: The personal dose monitoring rate and occupational health examination rate of medical radiation workers nationwide are relatively high, but the quality of lymphocyte chromosome aberration analysis, eye lens examination and thyroid color photograph examination needs to be further improved.

Healthy Tissue Damage Following Cancer Ion Therapy: A Radiobiological Database Predicting Lymphocyte Chromosome Aberrations Based on the BIANCA Biophysical Model.

Chromosome aberrations are widely considered among the best biomarkers of radiation health risk due to their relationship with late cancer incidence. In particular, aberrations in peripheral blood lymphocytes (PBL) can be regarded as indicators of hematologic toxicity, which is a major limiting factor of radiotherapy total dose. In this framework, a radiobiological database describing the induction of PBL dicentrics as a function of ion type and energy was developed by means of the BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations) biophysical model, which has been previously applied to predict the effectiveness of therapeutic-like ion beams at killing tumour cells. This database was then read by the FLUKA Monte Carlo transport code, thus allowing us to calculate the Relative Biological Effectiveness (RBE) for dicentric induction along therapeutic C-ion beams. A comparison with previous results showed that, while in the higher-dose regions (e.g., the Spread-Out Bragg Peak, SOBP), the RBE for dicentrics was lower than that for cell survival. In the lower-dose regions (e.g., the fragmentation tail), the opposite trend was observed. This work suggests that, at least for some irradiation scenarios, calculating the biological effectiveness of a hadrontherapy beam solely based on the RBE for cell survival may lead to an underestimation of the risk of (late) damage to healthy tissues. More generally, following this work, BIANCA has gained the capability of providing RBE predictions not only for cell killing, but also for healthy tissue damage.

Хромосомні аберації у лімфоцитах людини за зовнішнього та/або внутрішнього опромінення зразків крові 137Cs у модельних експериментах in vitro

The linear dependence of the yield of unstable chromosomal aberrations in human lymphocytes on the dose of prolonged external and/or internal irradiation of peripheral blood samples by 137Cs in the dose range of 0.09 - 0.54 Gy in vitro is presented. The higher cytogenetic efficiency of internal 137Cs irradiation is shown in comparison with external. It is shown that the cytogenetic efficiency of 137Cs in blood contamination is caused by influence on cells not only in the mitotic rest phase but during proliferation, within intracellular radioactivity through their cultivation. It is proposed to use the presented dose dependences of the yield of chromosomal aberrations in lymphocytes in vitro for human biological dosimetry during radiation accidents associated with prolonged external exposure or 137Cs incorporation to the body as a supplement to the results of physical dosimetry.

РОЛЬ МЕТИЛИРОВАНИЯ BAK1 В ИНДУКЦИИ ХРОМОСОМНЫХ АБЕРРАЦИЙ ПРИ ХРОНИЧЕСКОМ НИЗКОИНТЕНСИВНОМ ВНЕШНЕМ ОБЛУЧЕНИИ

Purpose: To study the relationship between the methylation status of the Bаk1 promoter and the frequency of chromosomal aberrations in human blood lymphocytes under chronic low-intensity external ionizing radiation.&#x0D; Material and methods: The study was performed on 41 people (31 men and 10 women, aged from 36 to 83 years) who are former or current employees of the Siberian Group of Chemical Enterprises, who have been exposed or haven't been exposed to chronic low-intensity external radiation in the course of their professional activities. The workers included in the study were divided into two groups: the first – 15 people who did not have exposure, the second – 26 people who had external exposure (gamma radiation, total dose 89–716 mSv). Whole blood was used to isolate DNA and evaluate chromosomal aberrations in lymphocytes. The methylation status of the Bаk1 promoter was determined using methylsensitive PCR, which was performed after pretreatment of the isolated DNA with methylsensitive AoxI restrictase. The obtained quantitative data were analyzed using the Statistica 10. The differences were considered statistically significant at p ≤ 0.05.&#x0D; Results: The methylation status of the Bаk1 promoter in the study groups does not differ (p = 0.18). The study of the effect of external radiation dose on the methylation status of the Bak1 promoter showed that the unmethylated promoter prevails in workers with an average radiation dose of 273.37 ± 43.82 mSv, while the methylated promoter – in workers with an average radiation dose of 183.63 ± 20.58 mSv (p = 0.03). The unmethylated promoter Bаk1 is associated with an increased frequency of chromatid fragments in the blood lymphocytes of group 2 workers (p = 0.03).&#x0D; Conclusion: The status of methylation of the Bаk1 promoter in human blood lymphocytes under chronic low-intensity ionizing radiation does not change, but it is observed to depend on the radiation dose and is associated with an increased frequency of chromosomal aberrations (chromatid fragments). Thus, the unmethylated Bаk1 promoter prevails when the external radiation dose is increased. An increase in the frequency of chromatid fragments is associated with an unmethylated Bаk1 promoter. In addition, exposure to chronic low-intensity external radiation is accompanied by a decrease in the frequency of chromosomal fragments in the blood lymphocytes of workers of the Siberian Group of Chemical Enterprises.

Biological features of blood lymphocytes of the primary patients with endometrial cancer

The aim: to examine the radiosensitivity of chromosomes of T-lymphocytes in the blood of primary patients with endometrial cancer depending on the radiation dose. It was expected that the investigations would reveal a cytogenetic parameter as a predictor of radiosensitivity in non-malignant cells of patients exposed to curative irradiation.&#x0D; Materials and methods. Blood samples from 20 primary patients and 30 conditionally healthy donors were examined. Peripheral blood T-lymphocytes culture test system with metaphase chromosome aberration analysis was used. X-ray test-irradiation was performed at G0-stage of the cell cycle in the dose range of 0.5–3.0 Gy.&#x0D; Results. It was shown that the spontaneous level of chromosome aberrations in lymphocytes of primary patients before anti-tumour therapy is 7,82±0,33 aberrations/100 metaphases. This is more than 2-fold higher than the upper limit of average population index and approximately 6-fold higher than the data of own control. In our study during X-ray irradiation of cells cultures of patients, it was found for the first time that the total frequency of radiation-induced chromosome aberrations obeys the classical linear quadratic dose dependence with a predominance of linear component values; the frequency of radiation markers – also linear quadratic dose dependence, but with a predominance of quadratic component.&#x0D; Conclusions. High specificity of T-lymphocyte chromosomes to exposure to ionizing radiation as well as strict dependence of chromosome aberration yield on exposure dose justify their use as predictors of radiosensitivity of healthy cells from the tumour environment. The revealed dependences of induction of chromosomal damage in T-lymphocytes of patients with endometrial cancer prove the need for a personalized approach to plan the course of radiation therapy