Damage In Peripheral Blood Lymphocytes Research Articles

Exploring cytokinesis block micronucleus assay in Croatia: A journey through the past, present, and future in biomonitoring of the general population

In this study, we used the cytokinesis-block micronucleus (CBMN) assay to evaluate the background frequency of cytogenetic damage in peripheral blood lymphocytes of the general population concerning different anthropometric data and lifestyle factors. The background frequency of CBMN assay parameters was analysed in 850 healthy, occupationally non-exposed male and female subjects (average age, 38±11 years) gathered from the general Croatian population from 2000 to 2023. The mean background values for micronuclei (MNi) in the whole population were 5.3±4.3 per 1000 binucleated cells, while the mean frequency of nucleoplasmic bridges (NPBs) was 0.7±1.3 and of nuclear buds (NBUDs) 3.1±3.2. The cut-off value, which corresponds to the 95th percentile of the distribution of 850 individual values, was 14 MNi, 3 NPBs, and 9 NBUDs. Results from our database also showed an association of the tested genomic instability parameters with age and sex but also with other lifestyle factors. These findings underscore the importance of considering several anthropometric and lifestyle factors when conducting biomonitoring studies. Overall, the normal and cut-off values attained here present normal values for the general population that can later serve as baseline values for further human biomonitoring studies either in Croatia or worldwide.

Effect of a phthalimide pesticide on human peripheral blood lymphocytes in vitro: induction of DNA damage

Introduction. Captan is a contact fungicide from the phthalimide class, used in agriculture to combat plant diseases. However, the question of its genotoxicity for humans remains open. Various studies examining the mutagenic activity of captan using different tests have yielded conflicting results. This study aims to investigate the potential of captan to induce DNA damage in human peripheral blood lymphocytes in vitro using single-cell alkaline gel electrophoresis.
 Material and methods. The DNA-damaging effect of captan (0; 2.5; 5.0; 10.0; 12.5 and 25 μg/ml) on lymphocytes of 26 donors was assessed with metabolic activation (+S9) and without it (–S9) using DNA comet analysis.
 Results. In the absence of metabolic activation, captan exhibited a pronounced genotoxic effect on cells. Statistically significant effects of captan was found on lymphocytes of all donors. The level of DNA-damaging effect on lymphocytes from 20 out of 26 donors depended on the concentration. The fold increase in the “%DNA in the tail of comets” indicator compared to the negative control at a concentration of 25 μg/ml varied in the range of 4,3–226 times. In the presence of the S9 mixture, weak but significant effects meeting the criteria for a positive response were detected only in three donors.
 Limitations. The genotoxicity of captan was studied only in vitro.
 Conclusion. Captan induces DNA damage in human peripheral blood lymphocytes in vitro in the absence of metabolic activation. Under conditions of metabolic activation, genotoxic effects were low. The levels of DNA damage in peripheral blood lymphocytes of different donors after exposure to captan varied markedly, indicating the necessity to consider individual sensitivity to genotoxicants when utilizing the DNA comet method to assess the potential mutagenic activity of chemicals.

Oxidative and DNA damage in obese patients undergoing bariatric surgery: A one-year follow-up study

The pathogenesis of obesity and related comorbidities has long been associated with oxidative stress. The excess of adipose tissue contributes to the production of free radicals that sustain both a local and a systemic chronic inflammatory state, whereas its reduction can bring to an improvement in inflammation and oxidative stress. In our work, using the fluorescent lipid probe BODIPY® 581/591 C11 and the γH2AX foci assay, a well-known marker of DNA double strand breaks (DSB), we evaluated the extent of cell membrane oxidation and DNA damage in peripheral blood lymphocytes of normal weight (NW) controls and obese patients sampled before and after bariatric surgery. Compared to NW controls, we observed a marked increase in both the frequencies of oxidized cells or nuclei exhibiting phosphorylation of histone H2AX in preoperatory obese patients. After bariatric surgery, obese patients, resampled over one-year follow-up, improved oxidative damage and reduced the presence of DSB. In conclusion, the present study highlights the importance for obese patients undergoing bariatric surgery to also monitor these molecular markers during their postoperative follow-up.

Utility of comet assay of DNA damage in the detection of malignant transformation of chronic liver cirrhosis

Early detection of hepatocellular carcinoma (HCC) remains a great challenge in laboratory medicine. This study aimed to assess the ability to use the degree of DNA damage (using the comet assay) for the early detection of malignant transformation of liver cirrhosis (LC) to HCC. We used alkaline comet assay for measuring DNA damage in peripheral blood lymphocytes in 50 patients with chronic LC and 50 patients with HCC. Fifty healthy individuals served as a control group. We compared the results of comet assay parameters with alpha fetoprotein as a relevant traditional marker. The HCC group was associated with a significantly higher tail intensity (p=.004), tail moment (p=.016), total area (p=.003), total intensity (p=.010), width (p=.005), and a significantly lower head intensity (.004) when compared to the LC group. Good areas under the curve (AUCs) were found for total area (0.890), head intensity (0.880) and tail intensity (0.880), making it useful for discrimination between HCC and LC groups. Lower head intensity, higher tail intensity, tail moment, total area and width were found to be independent risk factors for HCC on top of LC. Measuring DNA damage using the Alkaline comet assay technique can be considered a sensitive and reliable diagnostic tool for early neoplastic transformation of advanced LC.

Изучение бактериального микробиома мокроты больных раком легкого и его связи с повреждениями хромосом в лимфоцитах периферической крови

Микробиом респираторного тракта может оказывать значимое влияние на развитие ряда заболеваний дыхательной системы человека. Помимо дисбиотических изменений в составе микробиома пациентов отмечено, что многие бактерии обладают генотоксическим потенциалом и способны прямо или опосредованно повреждать геном в клетках организма хозяина. Цель исследования - изучить связь между составом микробиома мокроты и уровнем повреждений хромосом в лейкоцитах крови больных раком легкого (РЛ). Изучены таксономический состав бактериального микробиома мокроты, а также базовые частоты хромосомных аберраций (ХА) и микроядер (МЯ) в лимфоцитах крови 66 мужчин с диагнозом РЛ и у 62 здоровых доноров. Результаты секвенирования показали, что микробиом больных РЛ имеет признаки дисбиоза с достоверным увеличением содержания бактерий родов Streptococcus, Bacillus, Gemella и Haemophilus. У пациентов с РЛ выявлена прямая связь между частотой аберрантных метафаз в лимфоцитах и процентным содержанием в мокроте представителей рода Bacteroides. The microbiome of the respiratory tract can have a significant impact on the development of a number of diseases of the human respiratory system. In addition to dysbiotic changes in the composition of the microbiome of patients, it was noted that many bacteria have a genotoxic potential and are able to directly or indirectly damage the genome in the cells of the host organism. The aim of the study was to study the relationship between the composition of the sputum microbiome and the level of chromosome damage in the blood leukocytes of patients with lung cancer (LC). The taxonomic composition of the sputum bacterial microbiome, as well as the basic frequencies of chromosomal aberrations (CA) and micronuclei (MN) in blood lymphocytes of 66 men diagnosed with LC and 62 healthy donors were studied. The results of sequencing showed that the microbiome of LC patients has signs of dysbiosis with a significant increase in the content of bacteria of the genera Streptococcus, Bacillus, Gemella and Haemophilus. In patients with LC, a direct relationship was found between the frequency of aberrant metaphases in lymphocytes and the percentage of representatives of the genus Bacteroides in sputum.

DNA damage in peripheral blood lymphocytes of severely ill COVID-19 patients in relation to inflammatory markers and parameters of hemostasis.

Bearing in the mind that a variety of agents can contribute to genome instability, including viral infections, the aim of this study was to analyze DNA damage in hospitalized COVID-19 patients and its relationship with certain laboratory parameters. The potential impact of applied therapy and chest X-rays on DNA damage was also estimated. The study population included 24 severely COVID-19 patients and 15 healthy control subjects. The level of DNA damage was measured as genetic damage index (GDI) by comet assay. The standard laboratory methods and certified enzymatic reagents for the appropriate autoanalyzers were performed for the determination of the biochemical and hematological parameters. COVID-19 patients had significantly higher level of DNA damage compared with control subjects. The absolute number of neutrophil leukocytes was statistically higher, while the absolute number of lymphocytes was statistically lower in COVID-19 patients than in healthy controls. The analysis of the relationship between DNA damage and laboratory parameters indicated that GDI was positively correlated with interleukin 6 (IL-6) concentration and negatively with platelet count in COVID-19 patients. The level of DNA damage was slightly higher in female patients, in whom it was demonstrated a positive correlation of GDI with C-reactive protein (CRP) and procalcitonin. Likewise, there was a negative relationship of GDI and platelet count, and positive relationship of GDI and activated partial thromboplastin time (aPTT) in female population. The applied therapy (antibiotics, corticosteroid, anticoagulant, and antiviral therapy) as well as chest X rays has been shown to have genotoxic potential. The level of DNA damage significantly corresponds to the inflammatory markers and parameters of hemostasis in COVID-19 patients. In conclusion, inflammation, smoking habit, applied therapy, and chest X rays contribute to a higher level of DNA damage in COVID-19 patients.

Protective role of strawberry tree (Arbutus unedo L.) honey against cyto/genotoxic effects induced by ultraviolet B radiation in vitro

Strawberry tree (Arbutus unedo L.) honey (STH) is widely used as part of traditional medicine in the Mediterranean area, especially in the treatment of wounds, burns and infections. In this study, we investigated the cyto-/genoprotective properties of STH at cell level following short-term exposure to UVB radiation at 2 kJ/m2. Isolated human peripheral blood lymphocytes (PBL) were selected as model cells. Phenolics in STH were determined using an ultra-high-performance liquid chromatograph (UHPLC) coupled to a linear ion trap-Orbitrap hybrid mass spectrometer (LTQ Orbitrap MS), while homogentisic acid (HGA) was quantified using a gas chromatograph-mass spectrometer (GC-MS). Primary DNA damage in PBLs treated with STH before and after irradiation was assessed by alkaline comet assay, while their viability was determined using the apoptosis/necrosis assay. The levels of thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) were determined in plasma samples. STH applied as pre-treatment at a concentration equivalent to its average daily portion efficiently counteracted the cytotoxic and genotoxic effects and diminished UVB-induced oxidative stress. Post-radiation treatment with STH was not as beneficial. Protective effects could be associated to the complex phytochemical profile of STH and the high content of HGA (306.8 mg/kg). It was confirmed that an intake of a complex mixture of bioactive constituents as STH prior to potential cyto/genotoxic insults stimulated a broad-spectrum of protective mechanisms, including intracellular antioxidative defence and DNA repair systems that helped pre-treated cells to counteract harmful exposures more efficiently.

The effects of repeated brain MRI on chromosomal damage

BackgroundMagnetic resonance imaging (MRI) is currently considered a safe imaging technique because, unlike computed tomography, MRI does not expose patients to ionising radiation. However, conflicting literature reports possible genotoxic effects of MRI. We herein examine the chromosomal effects of repeated MRI scans by performing a longitudinal follow-up of chromosomal integrity in volunteers.MethodsThis ethically approved study was performed on 13 healthy volunteers (mean age 33 years) exposed to up to 26 3-T MRI sessions. The characterisation of chromosome damage in peripheral blood lymphocytes was performed using the gold-standard biodosimetry technique augmented with telomere and centromere staining.ResultsCytogenetic analysis showed no detectable effect after a single MRI scan. However, repeated MRI sessions (from 10 to 20 scans) were associated with a small but significant increase in chromosomal breaks with the accumulation of cells with chromosomal terminal deletions with a coefficient of 9.5% (95% confidence interval 6.5–12.5%) per MRI (p < 0.001). Additional exposure did not result in any further increase. This plateauing of damage suggests lymphocyte turnover. Additionally, there was no significant induction of dicentric chromosomes, in contrast to what is observed following exposure to ionising radiation.ConclusionsOur study showed that MRI can affect chromosomal integrity. However, the amount of damage per cell might be so low that no chromosomal rearrangement by fusion of two deoxyribonucleic breaks is induced, unlike that seen after exposure to computed tomography. This study confirms that MRI is a safe imaging technique.

Evaluation of DNA Damage in Peripheral Blood Lymphocytes Exposed to Gamma Radiation

Evaluation of DNA Damage in Peripheral Blood Lymphocytes Exposed to Gamma Radiation

Assays of genotoxic damage in peripheral blood lymphocytes of individuals occupationally exposed to different x-ray systems in hospital radiology departments

We obtained peripheral blood lymphocyte samples from individuals occupationally exposed to X-rays in hospital radiology departments that use different radiology systems: analog film (AF), computerized radiology (CR), or digital radiology (DR). The micronucleus test (MNT) and comet assay were performed on the samples. Micronucleus cell counts (means vs. controls, i.e., individuals not occupationally exposed to ionizing radiation) were as follows: AF, 1.96 ± 0.21 vs 1.2 ± 0.25; CR, 1.89 ± 0.15 vs 1.31 ± 0.36; and DR, 1.75 ± 0.11 vs 1.59 ± 0.32. For the comet assay, damage scores were as follows; AF, 0.84 ± 0.22 vs 0.47 ± 0.04; CR, 0.64 ± 0.26 vs 0.43 ± 0.04; and DR, 0.56 ± 0.19 vs 0.49 ± 0035. These findings were consistent with cytogenetic damage due to radiation exposure.

Long-Term Persistence of Increased Number of γH2AX+ Peripheral Blood Lymphocytes in Monkeys Exposed to Negative Factors of Space Flights: Ionizing Radiation and Simulated Hypogravity.

We studied the influence of ionizing radiation and hypogravity as negative factors of space flights on DNA damage in peripheral blood lymphocytes of rhesus monkeys at different times after exposure (from 1 to 446 days). The proportion of cells with high numbers of DNA double-strand breaks (DSB), positive for the surrogate DSB marker-protein γH2AX, was monitored using flow cytometry. Some animals were exposed to 7-day antiorthostatic hypokinesia simulating hypogravity, the others to a combined effect of antiorthostatic hypokinesia, whole-body γ-irradiation (2.34 cGy/h, dose 1 Gy), and irradiation of the head with 12C ions (450 MeV, dose 1 Gy). Exposure to antiorthostatic hypokinesia led to a significant increase in the proportion of γH2AX+ lymphocytes only on the first day after exposure, whereas after combined exposure, increased numbers of damaged lymphocytes were recorded up to 42 days after exposure.

Cisplatin Reduces the Frequencies of Radiotherapy-Induced Micronuclei in Peripheral Blood Lymphocytes of Patients with Gynaecological Cancer: Possible Implications for the Risk of Second Malignant Neoplasms.

Gynaecologic cancers are common among women and treatment includes surgery, radiotherapy or chemotherapy, where the last two methods induce DNA damage in non-targeted cells like peripheral blood lymphocytes (PBL). Damaged normal cells can transform leading to second malignant neoplasms (SMN) but the level of risk and impact of risk modifiers is not well defined. We investigated how radiotherapy alone or in combination with chemotherapy induce DNA damage in PBL of cervix and endometrial cancer patients during therapy. Blood samples were collected from nine endometrial cancer patients (treatment with radiotherapy + chemotherapy—RC) and nine cervical cancer patients (treatment with radiotherapy alone—R) before radiotherapy, 3 weeks after onset of radiotherapy and at the end of radiotherapy. Half of each blood sample was irradiated ex vivo with 2 Gy of gamma radiation in order to check how therapy influenced the sensitivity of PBL to radiation. Analysed endpoints were micronucleus (MN) frequencies, apoptosis frequencies and cell proliferation index. The results were characterised by strong individual variation, especially the MN frequencies and proliferation index. On average, despite higher total dose and larger fields, therapy alone induced the same level of MN in PBL of RC patients as compared to R. This result was accompanied by a higher level of apoptosis and stronger inhibition of cell proliferation in RC patients. The ex vivo dose induced fewer MN, more apoptosis and more strongly inhibited proliferation of PBL of RC as compared to R patients. These results are interpreted as evidence for a sensitizing effect of chemotherapy on radiation cytotoxicity. The possible implications for the risk of second malignant neoplasms are discussed.

UCTD and SLE patients show increased levels of oxidative and DNA damage together with an altered kinetics of DSB repair.

Immunological tolerance is a critical feature of the immune system; its loss might lead to an abnormal response of lymphocytes causing autoimmune diseases. One of the most important groups belonging to autoimmune disorders is the connective tissue diseases (CTD). CTD are classified among systemic rheumatic diseases and include pathologies such as systemic lupus erythematosus (SLE), and undifferentiated CTD (UCTD). In this study, we evaluated oxidative and genome damage in peripheral blood lymphocytes from patients with SLE and UCTD, further classified on the basis of disease activity and the presence/absence of a serological profile. Oxidative damage was evaluated in cell membrane using the fluorescent fatty acid analogue BODIPY581/591 C11. The percentage of oxidised lymphocytes in both SLE and UCTD patients was higher than in the control group, and the oxidative stress correlated positively with both disease activity and autoantibody profile. The γH2AX focus assay was used to quantify the presence of spontaneous double strand breaks (DSBs), and to assess the abilities of DSBs repair system after T cells were treated with mitomycin C (MMC). Subjects with these autoimmune disorders showed a higher number of γH2AX foci than healthy controls, but no correlation with diseases activity and presence of serological profile was observed. In addition, patients displayed an altered response to MMC-induced DSBs, which led their peripheral cells to greatly increase apoptosis. Taken together our results confirmed an interplay among oxidative stress, DNA damage and impaired DNA repair, which are directly correlated to the aggressiveness and clinical progression of the diseases. We propose the evaluation of these molecular markers to better characterise SLE and UCTD, aiming to improve the treatment plan and the quality of the patients' life.

Influence of dietary fish oil supplementation on DNA damage in peripheral blood lymphocytes of nine healthy dogs.

BackgroundFish oil (FO) supplementation as a source of omega 3 fatty acids is associated with beneficial effects on health. However, high unsaturated fatty acid content in the diet could result in increased lipid peroxidation and damage to proteins, lipids and DNA. We evaluated the effect of dietary FO supplementation on DNA damage in peripheral blood lymphocytes of dogs. Additionally, we determined the effect of FO supplementation on lipid peroxidation and lipid profile of these dogs.MethodsHealthy male dogs (n = 9) were randomly assigned to one of two diets during 90 days: control (CG, n = 4), based on a commercial food, and FO (FOG, n = 5), the same food supplemented with 1000 mg FO. Blood samples were collected on days −1, 30, 60 and 90. DNA damage was assessed with the comet assay, and the damage index was obtained. Malondialdehyde (MDA) levels were determined as an indicator of lipid peroxidation. Lipid profile determination included serum triglyceride, cholesterol, low‐density lipoprotein and high‐density lipoprotein levels (HDL).ResultsDamage index values (arbitrary units) were lower in FOG on day 30 (CG, 13.7 ± 2.5; FOG, 6.5 ± 2.5), 60 (CG, 14.7 ± 2.5; FOG, 3.5 ± 2.5) and 90 (CG, 15.5 ± 2.5; FOG, 3.0 ± 2.5) compared with CG (treatment × time interaction, p < 0.01). Serum MDA and HDL concentrations were lower in FOG compared with CG on day 60 and 90 (treatment × time interaction, p < 0.05).ConclusionThese findings suggest that dietary FO supplementation did not induce DNA damage in peripheral blood lymphocytes of healthy dogs, but rather reduced it.

Evaluating the genetic basiss of anti-cancer property of Taxol in Saccharomyces cerevisiae model.

Taxol has been regarded as one of the most successful anti-cancer drugs identified from natural sources to date. Although Taxol is known to sensitize cells by stabilizing microtubules, its ability to cause DNA damage in peripheral blood lymphocytes and to induce oxidative stress and apoptosis indicates that Taxol may have other modes of cytotoxic action. This study focuses on identifying the additional targets of Taxol that may contribute to its multifaceted cell killing property, using Saccharomyces cerevisiae. We show that yeast oxidative stress response mutants (sod1Δ, tsa1Δ and cta1Δ) and DNA damage response mutants (mre11∆, sgs1∆ and sub1∆) are highly sensitive to Taxol. Our results also show that Taxol increases the level of reactive oxygen species (ROS) in yeast oxidative stress response mutant strains. Further, 4',6-Diamidino-2'-phenylindole (DAPI) and acridine orange/ethidium bromide (AO/EB) staining show that Taxol induces apoptotic features such as nuclear fragmentation and chromatin condensation in DNA repair mutants. On the whole, our results suggest that Taxol's cytotoxic property is attributed to its multifaceted mechanism of action. Yeast S. cerevisiae anti-oxidant and DNA repair gene mutants are sensitive to Taxol compared to wild-type, suggesting yeast model can be used to identify the genetic targets of anti-cancer drugs.

Strawberry (Fragaria ananassa duch.) Alba extract attenuates DNA damage in lymphocytes of patients with Alzheimer's disease.

Increased levels of oxidative stress and oxidative DNA damage are common features in the pathology of Alzheimer's disease (AD) found in neurons and peripheral cells like peripheral blood lymphocytes (PBL). Natural products such as strawberry cultivar Alba are an important source of bioactive nutrients that could help in lowering both the oxidative stress and DNA damage levels. The objective was to estimate the effects of Alba extract on DNA damage in peripheral blood lymphocytes of sporadic AD (aged 60-84years) patients, and healthy elderly (aged 69-83years) and young (aged 21-30years) individuals in in vitro conditions. Comet assay was used as a sensitive technique for the evaluation of PBL DNA damage levels. Reduction of basal DNA damage level in PBL was shown in the young group after the incubation with Alba extract ranging from 25 to 200μg/ml, with 100μg/ml being the most effective concentration. Selected Alba extract of 100μg/ml was further used for PBL treatment of AD and healthy elderly age matched group, displaying potential to significantly attenuate DNA damage levels in both groups (p<.05). Alba extract displayed biological activity against oxidative DNA damage, suggesting that its functional ingredients may have beneficial health effects. PRACTICAL APPLICATIONS: The data obtained in this preliminary study displayed that strawberry Alba extract is efficient against DNA damage induced by endogenous and exogenous oxidative stress in peripheral blood lymphocytes of Alzheimer`s disease in vitro. An active area of future research of Alba cultivar should be to determine the trials in in vivo systems. Our findings also suggest that Alba cultivar's functional ingredients potentially may have beneficial health effects in AD.

Assessment of DNA damage through micronucleus studies in subjects exposed to formalin

Background: Formaldehyde (FA) is the reactive and simplest of all the aldehydes. It is used as a preservative in anatomy, pathology and forensic laboratories. The international agency for research on cancer has classified FA as a carcinogen that can cause nasopharyngeal carcinoma, Leukaemia, Liver and pancreatic cancer. Objective And Method: The aim of the study was to assess the DNA damage in peripheral blood lymphocytes and in buccal cells by Micronucleus assay in Formalin exposed workers of Anatomy, Pathology and Forensic laboratories and compare with the control group, and also to analyze the relationship between frequency of Micronuclei and duration of exposure to formalin. Results: The mean and standard deviation (SD) of micronuclei in peripheral blood of exposed was 8.35 and in controls was 4.18. There was a significant increase in the frequency of MN in exposed group when compared with the comparison group (p&lt;0. 5876). Pearson’s correlation test showed a positive correlation between the years of FA exposure and the number of micronuclei in buccal cells and peripheral blood indicating that DNA damage due to FA was directly proportional to the duration of exposure (r=0.8, 0.9). Conclusion: The present study was done to assess the DNA damage in people who were exposed to FA and a control group not exposed to FA by buccal cell and peripheral blood Micronucleus Assay. There was a significant increase in the MN in people exposed to FA which was directly proportional to the duration of exposure.

Genotoxic biomarkers in patients on hemodialiasis

It is generally recognized that genotoxic damage have essential etiopathogenetic significance, and its prevention is an important measure to preserve human life and health. In the framework of this concept, literature information on studies of genotoxic biomarkers in patients with various hemodialysis regiments has been reviewed and summarized, and ways to prevent detectable genotoxicity have been identified. Based on the analysis of the known data, it was concluded that patients of this group have an increased level of DNA and chromosome damage in peripheral blood lymphocytes. Based on the results of individual studies, it was shown that one of the strategies for reducing genotoxicity may be the improvement of hemodialysis therapy methods and regimes, as well as pharmacological and nutritional correction of genotoxic effects.

Prospective evaluation of functional brain activity and oxidative damage in breast cancer: changes in task-induced deactivation during a working memory task.

Cancer-related cognitive dysfunction is an important issue for breast cancer survivors. Previous research has identified both cross-sectional and longitudinal alterations in brain function related to cancer status and treatment. In this study, we prospectively collected functional magnetic resonance imaging data in breast cancer cases treated with adjuvant chemotherapy and in controls with no cancer history during a working memory task. Data and blood specimens were collected immediately prior to the start of treatment (baseline) and following completion of treatment (follow-up), and at yoked intervals for controls. In secondary analysis we assessed the levels of oxidative DNA damage in peripheral blood lymphocytes of cases and controls using the Comet assay. A significant group*time interaction revealed reduced deactivation in the superior frontal gyrus in the controls at follow-up, in contrast to cases, who exhibited similar magnitude of deactivation at baseline and follow-up. Working memory performance indicated a significant improvement in the controls at follow-up, and no change in performance in cases. In secondary analyses, oxidative DNA damage levels were elevated in the cases at follow-up compared to controls, but no associations were found between the Comet assay variables and functional imaging at either time-point or group. In light of previous reports on task induced deactivations, our findings reflect continuing effortful processing at follow-up in the breast cancer group, with relatively less effortful processing in the control group given the reduced novelty and practice effects from the baseline to follow-up.

Study of the DNA Damage in Peripheral Blood Lymphocytes Using Micronucleus Test in Residents of the Techa Riverside Villages Who Were Chronically Exposed in Utero and Postnatally

The paper presents the results of the assessment of the frequency of the peripheral blood Т lymphocytes with micronuclei in Techa riverside residents who were chronically exposed in the 1950s. The study was performed 40–60 years after the onset of exposure. The exposed persons consisted of two groups: individuals who were first exposed in utero and then postnatally, and individuals who had only postnatal exposure. Cumulative dose to RBM in exposed persons varied within the range 0.001–4 Gy. A comparison group was also formed. It included individuals comparable in age, sex, and living conditions, but these people were not affected by accidental exposure. Findings of the study demonstrated that the frequency of lymphocytes with micronuclei was significantly higher in exposed women as compared to exposed men. The frequency of lymphocytes with micronuclei was significantly lower in those exposed in utero relative to the postnatally exposed persons and members of the comparison group. This decrease was observed both in women and in men. The study of the contribution of the cumulative dose to RBM revealed an increase in frequency of the lymphocytes with micronuclei in women exposed at doses of 0.1–0.49 Gy.