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Benign tumors, but rarely cancer, are common in patients with tuberous sclerosis complex (TSC). Blood samples from patients undergoing treatment for TSC at our institution were analyzed for their individual sensitivity to ionizing radiation. Blood samples were collected from 13 adult patients with TSC. The samples were irradiated ex vivo and analyzed by 3-color fluorescence in situ hybridization. In each patient, aberrations were analyzed in 200 metaphases of chromosomes 1, 2, and 4 and scored as breaks. Radiosensitivity was determined by mean breaks per metaphase (B/M) and compared to both healthy donors and oncologic patients. The radiosensitivity (B/M) of the TSC patient cohort (n = 13; female: 46.2%, B/M: 0.48 ± 0.11) was clearly increased compared to healthy individuals of similar age (n = 90; female: 54.4%; B/M: 0.40 ± 0.09; p = 0.001). There was no difference compared to age-matched oncological patients (n = 78; female: 67.9%; B/M 0.49 ± 0.14; p = 0.246). Similarly, the proportion of radiosensitive (B/M > 0.5) and distinctly radiosensitive individuals (B/M > 0.6) was increased in the TSC and oncological patient cohorts (TSC: 30.8% and 7.7%, oncological patients: 46.2% and 14.1%) compared to the healthy individuals (11.1% and 2.2%). Although patients with TSC develop mostly benign and rarely malignant tumors, they are similarly sensitive to radiation as patients with malignant tumors. [ABSTRACT FROM AUTHOR]

Purpose: Ionizing radiation-based technologies are extensively used in the diagnosis and treatment of diseases. While utilizing the technologies, exposure to a certain amount of radiation is unavoidable. Data can be obtained from participants who received radiation during medical imaging and therapeutic purposes to predict the effects of low-dose radiation. Methods: To understand the effects of low-dose radiation, participants (n = 22) who received radioactive I-131 for scan/therapy were used as a model in this study. Blood samples were drawn pre- and post-administration of I-131. Biological effects were measured using markers of DNA damage (γ-H2AX, micronucleus (MN), and chromosomal aberrations (CA)) and response to damage through gene expression changes (ATM, CDKN1A, DDB2, FDXR, and PCNA) in blood samples. Results: Mean frequency of γ-H2AX foci in pre-samples was 0.28 ± 0.16, and post-samples were 1.03 ± 0.60. γ-H2AX foci frequency obtained from post-samples showed significant (p < 0.0001) and a heterogeneous increase in all the participants (received I-131 for scan/therapy) when compared to pre-samples. A significant increase (p < 0.0001) in MN and CA frequency was also observed in participants who received the I-131 therapy. Gene expression analysis indicates that all genes (ATM, CDKN1A, DDB2, FDXR, and PCNA) were altered in post-samples, although with varying degrees, suggesting that the cellular responses to DNA damage, such as damage repair, cell cycle regulation to aid in repair and apoptosis are increased, which priority is given to repair, followed by apoptosis. Conclusion: The results of this study indicate that the participants who received I-131 (low doses of β- and γ-radiation) can produce substantial biological effects. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Glyphosate and 2,4-dichlorophenoxyacetic acid (2,4-D) are the most widely used pesticides in the world. In this work, the cytogenotoxic potential of these herbicides and their binary mixtures was investigated using A. cepa test. 2,4-D was assayed at 0.4 – 400 μg L−1 and glyphosate at 0.65 – 650 μg L−1 concentration range. The concentrations evaluated cover those permitted by Brazilian legislation for the protection of aquatic life and human health. Sixteen binary mixtures were examined to replicate different contamination scenarios. When analyzed separately, 2,4-D at 400 μg L−1 inhibited the mitotic index, while glyphosate at 0.65 and 65 μg L−1 increased it. In addition, the herbicides increased the frequency of chromosomal aberrations (2,4-D at 0.4, 4, and 40 μg L−1 and glyphosate at 0.65, 65, and 650 μg L−1) and micronuclei (2,4-D at 400 μg L−1 and glyphosate at 650 μg L−1). Regarding the mixtures, six of them were cytotoxic while eight were genotoxic. Additive, synergistic, or potentiated effects were observed. However, none of the mixtures tested increased the frequency of micronuclei. The results showed that even concentrations allowed by Brazilian legislation pose a potential risk to exposed organisms. There is little research on the cytogenotoxic effects of 2,4-D + glyphosate mixtures, so this is the first study to analyze a large number of combinations. The detection of additive, synergistic, or potentiated toxicities highlights the need for better pesticide legislation and discussions among regulators and environmental managers regarding pesticide mixtures in water. [ABSTRACT FROM AUTHOR]

Abstract Benign tumors, but rarely cancer, are common in patients with tuberous sclerosis complex (TSC). Blood samples from patients undergoing treatment for TSC at our institution were analyzed for their individual sensitivity to ionizing radiation. Blood samples were collected from 13 adult patients with TSC. The samples were irradiated ex vivo and analyzed by 3-color fluorescence in situ hybridization. In each patient, aberrations were analyzed in 200 metaphases of chromosomes 1, 2, and 4 and scored as breaks. Radiosensitivity was determined by mean breaks per metaphase (B/M) and compared to both healthy donors and oncologic patients. The radiosensitivity (B/M) of the TSC patient cohort (n = 13; female: 46.2%, B/M: 0.48 ± 0.11) was clearly increased compared to healthy individuals of similar age (n = 90; female: 54.4%; B/M: 0.40 ± 0.09; p = 0.001). There was no difference compared to age-matched oncological patients (n = 78; female: 67.9%; B/M 0.49 ± 0.14; p = 0.246). Similarly, the proportion of radiosensitive (B/M > 0.5) and distinctly radiosensitive individuals (B/M > 0.6) was increased in the TSC and oncological patient cohorts (TSC: 30.8% and 7.7%, oncological patients: 46.2% and 14.1%) compared to the healthy individuals (11.1% and 2.2%). Although patients with TSC develop mostly benign and rarely malignant tumors, they are similarly sensitive to radiation as patients with malignant tumors.

Ganoderma lucidum has had great importance in healthcare in the Chinese for many decades. Polysaccharides and triterpenoids are one of the most important components of G. lucidum. Biological evidence indicates that this mushroom can be a promising treatment in many cancer cases and reduce the toxic effect of chemotherapy and radiotherapy if taken synchronously. This study highlights preparing an extract with therapeutic effects capable of removing free radicals and protecting cell membranes from hyperoxidation effects. The antitumor effect was evaluated on two types of cancer cell lines in vitro, Human Oral Squamous Cell Carcinoma (HOSCC) and Human Skin Squamous Cell Carcinoma (HSSCC), at different concentrations 0.0-1600 µg/mL. Antioxidant by DPPH assay was assessed at concentrations from 0.0-500 µg/mL, in addition to their effects on cytogenetic indicators such as mitotic index (MI), blastogenic index (BI) and total chromosomal aberration (TCAs) for three types of extracts (ethanol extract, water extract and acidified water extract). The results recorded an increase in the antioxidant activity of the three extracts, and that the acidified water extract had the highest effect, reaching a killing rate of 78.53% for the acidified water extract on the HOSCC cell line. Chromosomal stability indicates that the three extracts enhanced the cytogenetics parameters and supported chromosomal stability by increasing both mitotic index (MI) and blastogenic index (BI), while reducing chromosomal aberrations.

Abstract Background Toxicity by pesticide has become a global health issue and leaves a harmful impact on human health via various ways. The people exposed to pesticides in the rural population get affected by the harmful effects of it as they enter the human body system through skin, inhalation, oral administration, food chain and many more ways. The present work is designed to study the toxic effect of endosulfan in male (n=30) and female (n=30) Swiss albino mice. Endosulfan was administered by oral gavage (oral administration) method, at the dose of 3.5 mg/Kg body weight daily for period of 3 weeks, 5 weeks and 7 weeks. After the completion of the treatment, the mice were sacrificed and their ovary and testis tissues were dissected out to check the degeneration. The blood was collected for karyotyping, biochemical and hormonal analysis of pesticide induced genotoxicity. After 7 weeks of administration with Endosulfan, various abnormalities were observed in male and female mice. Results Treatment with endosulfan at the dose of 3.5 mg/Kg body weight caused a higher degree of degeneration in the reproductive organ of Swiss albino mice . Treatment by this pesticide generated degeneration in long duration of dosage for 3,5 and 7 weeks. Ovaries of endosulfan administered groups showed degenerated germinal epithelium, Graffian follicles and corpus luteum. In testis of endosulfan treated mice, microscopic examination showed that there is significant damage and reduction in the tissue of seminiferous tubules and primordial germ cells. High degree of degeneration caused the disarrangement and deformation of spermatogonia with the decrease in the number of Sertoli cells. Biochemical and hormonal properties was also affected by endosulfan treatment. There was significant 5 folds decrease in the testosterone value of endosulfan in 7 weeks treated mice in comparison to control (p

Abstract Astronauts travelling in space will be exposed to mixed beams of particle radiation and photons. Exposure limits that correspond to defined cancer risk are calculated by multiplying absorbed doses by a radiation-type specific quality factor that reflects the biological effectiveness of the particle without considering possible interaction with photons. We have shown previously that alpha radiation and X-rays may interact resulting in synergistic DNA damage responses in human peripheral blood lymphocytes but the level of intra-individual variability was high. In order to assess the variability and validate the synergism, blood from two male donors was drawn at 9 time points during 3 seasons of the year and exposed to 0–2 Gy of X-rays, alpha particles or 1:1 mixture of both (half the dose each). DNA damage response was quantified by chromosomal aberrations and by mRNA levels of 3 radiation-responsive genes FDXR, CDKN1A and MDM2 measured 24 h post exposure. The quality of response in terms of differential expression of alternative transcripts was assessed by using two primer pairs per gene. A consistently higher than expected effect of mixed beams was found in both donors for chromosomal aberrations and gene expression with some seasonal variability for the latter. No synergy was detected for alternative transcription.

Aging is a complex process that features a functional decline in many organelles. Various factors influence the aging process, such as chromosomal abnormalities, epigenetic changes, telomere shortening, oxidative stress, and mitochondrial dysfunction. Mitochondrial dysfunction significantly impacts aging because mitochondria regulate cellular energy, oxidative balance, and calcium levels. Mitochondrial integrity is maintained by mitophagy, which helps maintain cellular homeostasis, prevents ROS production, and protects against mtDNA damage. However, increased calcium uptake and oxidative stress can disrupt mitochondrial membrane potential and permeability, leading to the apoptotic cascade. This disruption causes increased production of free radicals, leading to oxidative modification and accumulation of mitochondrial DNA mutations, which contribute to cellular dysfunction and aging. Mitochondrial dysfunction, resulting from structural and functional changes, is linked to age-related degenerative diseases. This review focuses on mitochondrial dysfunction, its implications in aging and age-related disorders, and potential anti-aging strategies through targeting mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

This study aimed to investigation the effect of environmental changing associated with the elevation gradient on cytogenetic traits of Taraxacum officinale during its invasion in high altitude areas. We chose common dandelion as the object of research, because representatives of this species are able to inhabit a large range of elevations. The cytogenetic characteristics of the plants growing at altitudes of 200, 600, 1300, 2050, 2700 and 3050 m a.s.l in the Central Caucasus region have been studied. We determined the frequency of micronuclei, chromosomal aberrations, mitotic index and chromosome number in the cells of the apical root meristem using seed progeny of plants growing at different elevations. In the populations of natural habitats studied by us, all individuals were triploid with the exception of single ones. The level of ploidy increased in accordance with the altitude gradient when T. officinale invade in the disturbed highland areas. In the seed progeny of highland plants cell proliferation and the ratio of mitosis phases do not change along the elevation gradient. The frequency of chromosome aberrations increased by 1.3–4.6 times in the highland populations. The main types of mutations were fragments, lost and lagging chromosomes. The reasons for this are the influence of unfavorable conditions of high-altitude areas and high level of ploidy in plants of these populations. Despite the significant increase in the frequency of chromosome aberrations, no similar increase in the frequency of micronuclei resulting from these mutations was found. [ABSTRACT FROM AUTHOR]

Gasoline station attendants are exposed to numerous chemicals that might have genotoxic and carcinogenic potential, such as benzene in fuel vapor and particulate matter and polycyclic aromatic hydrocarbons in vehicle exhaust emission. According to IARC, benzene and diesel particulates are Group 1 human carcinogens, and gasoline has been classified as Group 2A "possibly carcinogenic to humans." At gas stations, self-service is not implemented in Turkey; fuel-filling service is provided entirely by employees, and therefore they are exposed to those chemicals in the workplace during all working hours. Genetic monitoring of workers with occupational exposure to possible genotoxic agents allows early detection of cancer. We aimed to investigate the genotoxic damage due to exposures in gasoline station attendants in Turkey. Genotoxicity was evaluated by the Comet, chromosomal aberration, and cytokinesis-block micronucleus assays in peripheral blood lymphocytes. Gasoline station attendants (n = 53) had higher tail length, tail intensity, and tail moment values than controls (n = 61). In gasoline station attendants (n = 46), the frequencies of chromatid gaps, chromosome gaps, and total aberrations were higher compared with controls (n = 59). Increased frequencies of micronuclei and nucleoplasmic bridges were determined in gasoline station attendants (n = 47) compared with controls (n = 40). Factors such as age, duration of working, and smoking did not have any significant impact on genotoxic endpoints. Only exposure increased genotoxic damage in gasoline station attendants independently from demographic and clinical characteristics. Occupational exposure-related genotoxicity risk may increase in gasoline station attendants who are chronically exposed to gasoline and various chemicals in vehicle exhaust emissions. [ABSTRACT FROM AUTHOR]

Astronauts travelling in space will be exposed to mixed beams of particle radiation and photons. Exposure limits that correspond to defined cancer risk are calculated by multiplying absorbed doses by a radiation-type specific quality factor that reflects the biological effectiveness of the particle without considering possible interaction with photons. We have shown previously that alpha radiation and X-rays may interact resulting in synergistic DNA damage responses in human peripheral blood lymphocytes but the level of intra-individual variability was high. In order to assess the variability and validate the synergism, blood from two male donors was drawn at 9 time points during 3 seasons of the year and exposed to 0–2 Gy of X-rays, alpha particles or 1:1 mixture of both (half the dose each). DNA damage response was quantified by chromosomal aberrations and by mRNA levels of 3 radiation-responsive genes FDXR, CDKN1A and MDM2 measured 24 h post exposure. The quality of response in terms of differential expression of alternative transcripts was assessed by using two primer pairs per gene. A consistently higher than expected effect of mixed beams was found in both donors for chromosomal aberrations and gene expression with some seasonal variability for the latter. No synergy was detected for alternative transcription. [ABSTRACT FROM AUTHOR]

Lymphopenia is now generally recognized as a negative prognostic factor in radiotherapy. Already at the beginning of the century we demonstrated that high-energy carbon ions induce less damage to the lymphocytes of radiotherapy patients than X-rays, even if heavy ions are more effective per unit dose in the induction of chromosomal aberrations in blood cells irradiated ex-vivo. The explanation was based on the volume effect, i.e. the sparing of larger volumes of normal tissue in Bragg peak therapy. Here we will review the current knowledge about the difference in lymphopenia between particle and photon therapy and the consequences. There is nowadays an overwhelming evidence that particle therapy reduces significantly the radiotherapy-induced lymphopenia in several tumor sites. Because lymphopenia turns down the immune response to checkpoint inhibitors, it can be predicted that particle therapy may be the ideal partner for combined radiation and immunotherapy treatment and should be selected for patients where severe lymphopenia is expected after X-rays. [ABSTRACT FROM AUTHOR]

Topotecan administered intraperitoneally at single doses of 0.25, 0.5, and 1 mg/kg induced chromosomal aberrations in bone marrow cells of F1(CBA×C57BL/6) hybrid mice in a dose-dependent manner. A tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitor, an usnic acid derivative OL9-116 was inactive in a dose range of 20-240 mg/kg, but enhanced the cytogenetic effect of topotecan (0.25 mg/kg) at a dose of 40 mg/kg (per os). The TDP1 inhibitor, a coumarin derivative TX-2552 (at doses of 20, 40, 80, and 160 mg/kg per os), increased the level of aberrant metaphases induced by topotecan (0.25 mg/kg) by 2.1-2.6 times, but was inactive at a dose of 10 mg/kg. The results indicate that TDP1 inhibitors enhance the clastogenic activity of topotecan in mouse bone marrow cells in vivo and are characterized by different dose profiles of the co-mutagenic effects. [ABSTRACT FROM AUTHOR]

Among the compounds present in necro-leachate, a liquid released during the process of decomposition of the human body, are the biogenic amines cadaverine and putrescine. Although some studies on necro-leachate have indicated a potential ecotoxicological and public health risk associated with it, the research on this type of contamination is still rather limited. This study presents information about the phytotoxic and cytogenotoxic potential of cadaverine and putrescine, evaluated separately and within a mixture. Phytotoxicity was evaluated through a germination test, the initial growth of seedlings with Lactuca sativa, and cytogenotoxicity through chromosomal aberration and micronucleus tests with Allium cepa. The L. sativa results showed a phytotoxic effect for the evaluated amines, by reducing root (> 90%) and hypocotyl (> 80%) elongation. The co-exposure of cadaverine and putrescine potentiated cytogenotoxic activity by aneugenic action in the meristematic cells of A. cepa. From this result, it is possible to infer the eco-toxicogenic potential of cadaverine and putrescine. This study not only highlights the importance of the phytotoxic and cytogenotoxic effects of these amines but also emphasizes the urgent need for further investigation into contamination originating from cemetery environments. By evaluating the risks associated with necro-leachate, this research is aimed at informing global efforts to protect ecological and public health. [ABSTRACT FROM AUTHOR]

Due to the large number of nuclear power plants around the globe and the growing threat of radioactive accidents, a complex assessment of the biological consequences of the Chornobyl disaster is a relevant issue. Study of mutagenic activity of prolonged and chronic action of radionuclide pollution of soil in the Chornobyl Exclusion Zone long after the accident will allow us to identify the current level of threat they pose to the human genome and can reveal specific cytogenic markers of radionuclide environmental pollution. For this purpose, we germinated seeds of wheat of soft winter varieties Smuhlianka and Bohdana in soil samples from the Chornobyl Exclusion Zone 35 years after the disaster. Specific activity of Cs-137 and Sr-90 accounted for 4.5–28.2 kBq/kg. To determine the frequency and range of chromosomal aberrations, we used the anaphase-telophase method. In aberrant cells, we studied extracellular distribution of chromosomal disorders. The frequency of aberrant cells was 3.53–7.55 times above the spontaneous level. High mutagenic activity remained in the conditions of the lowest density of radionuclide pollution of soil. The range of chromosomal disorders mostly included paired fragments and bridges and containd chromosomal acentric rings, binding of chromosomes, myocardium, and lagging and leading chromosomes. Radionuclide pollution in the Chornobyl Exclusion Zone induced multiple cellular aberrations in the rhizome meristem, the share of which was the highest in case of low specific radionuclide pollution of soil, and exhibited a tendency towards decrease against the background of the highest density of radionuclides. Pollution of the environment with radionuclides as a result of disasters at nuclear energy objects poses a threat to the human genome and is a global problem, requiring state support to solve through systematic genetic monitoring in readionuclide-polluted territories and areas adjacent to them.

Genome editing, notably CRISPR (cluster regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9), has revolutionized genetic engineering allowing for precise targeted modifications. This technique's combination with human induced pluripotent stem cells (hiPSCs) is a particularly valuable tool in cerebral organoid (CO) research. In this study, CRISPR/Cas9-generated fluorescently labeled hiPSCs exhibited no significant morphological or growth rate differences compared with unedited controls. However, genomic aberrations during gene editing necessitate efficient genome integrity assessment methods. Optical genome mapping, a high-resolution genome-wide technique, revealed genomic alterations, including chromosomal copy number gain and losses affecting numerous genes. Despite these genomic alterations, hiPSCs retain their pluripotency and capacity to generate COs without major phenotypic changes but one edited cell line showed potential neuroectodermal differentiation impairment. Thus, this study highlights optical genome mapping in assessing genome integrity in CRISPR/Cas9-edited hiPSCs emphasizing the need for comprehensive integration of genomic and morphological analysis to ensure the robustness of hiPSC-based models in cerebral organoid research. [ABSTRACT FROM AUTHOR]

Simple Summary: Organotypic features such as intratumoral thymopoiesis make thymomas (THs) unique tumors. Their remarkable histological heterogeneity and low mutational burden have largely precluded personalized therapies. Although most thymomas do not harbor known oncogenic driver mutations, common non-mutational key features such as chromosomal, epigenetic, and metabolic alterations are emerging that converge into a limited number of critical cellular pathways that may provide opportunities for therapeutic interventions. In this review, we have attempted to integrate the existing knowledge of TH biology into a broader picture and highlight opportunities for targeted treatment options in these non-mutated tumors. Thymomas (THs) are a unique group of heterogeneous tumors of the thymic epithelium. In particular, the subtypes B2 and B3 tend to be aggressive and metastatic. Radical tumor resection remains the only curative option for localized tumors, while more advanced THs require multimodal treatment. Deep sequencing analyses have failed to identify known oncogenic driver mutations in TH, with the notable exception of the GTF2I mutation, which occurs predominantly in type A and AB THs. However, there are multiple alternative non-mutational mechanisms (e.g., perturbed thymic developmental programs, metabolism, non-coding RNA networks) that control cellular behavior and tumorigenesis through the deregulation of critical molecular pathways. Here, we attempted to show how the results of studies investigating such alternative mechanisms could be integrated into a current model of TH biology. This model could be used to focus ongoing research and therapeutic strategies. [ABSTRACT FROM AUTHOR]

The present study focuses on investigating the interaction between radiation and biological systems, specifically examining the detrimental effects of radiation. This approach has proven to be effective in determining the optimal tolerance range of radiation on plants, which can lead to the development of beneficial characteristics and help improve the narrow genetic base. The study was conducted on Salvia hispanica L., a medicinally important plant. Inbred seeds of Salvia hispanica L. were subjected to five different doses of gamma rays (50, 100, 150, 200, 250 Gy) using a Co-60 source with a gamma irradiator of 7.247 k rate. The seeds were sown in triplicate, along with a control set. Various characteristics were assessed, including germination percentage, survival percentage, presence of chlorophyll mutants, and plant height. The results indicate that lower doses of gamma irradiation (LD50) have detrimental effects on several plant attributes, such as seed germination, survivability, inflorescence size, and pollen fertility. Chromosomal abnormalities were also observed, with an increase in their occurrence corresponding to higher doses of gamma radiation. Germination percentage and survivability were found to decrease as the dose of gamma radiation increased. The dose of 50 Gy resulted in the highest level of genetic variability. Additionally, compared to the control group, a significant percentage of chromosomal abnormalities, particularly stickiness and scattering, was observed at a dose of 250 Gy. Lower doses of gamma radiation (specifically 50 and 100 Gy) showed statistically significant (p>0.5) positive responses in Salvia plants, including plant height, leaf area, leaf mutants, inflorescence axis, and seed size. On the other hand, higher doses of radiation proved to be fatal for the plants. In summary, this study provides valuable insights into the effects of gamma radiation on Salvia hispanica L., highlighting the optimal dose range for inducing beneficial changes in plant characteristics while also emphasizing the harmful consequences associated with higher doses of radiation. [ABSTRACT FROM AUTHOR]

Background: Copy number variation sequencing (CNV-seq) is a powerful tool to discover structural genomic variation, but limitations associated with its retrospective study design and inadequate diversity of participants can be impractical for clinical application. Aim: This study aims to use CNV-seq to assess chromosomal aberrations in pregnant Vietnamese women. Materials & methods: A large-scale study was conducted on 3776 pregnant Vietnamese women with abnormal ultrasound findings. Results: Chromosomal aberrations were found in 448 (11.86%) women. Of these, 274 (7.26%) had chromosomal aneuploidies and 174 (4.61%) carried pathogenic/likely pathogenic CNVs. Correlations were established between chromosomal aberrations and various phenotypic markers. Conclusion: This comprehensive clinical study illuminates the pivotal role of CNV-seq in prenatal diagnosis for pregnancies featuring fetal ultrasound anomalies. Summary points Main topics In this study, we conducted a large clinical study of 3776 pregnant Vietnamese women to assess chromosomal aberrations using copy number variation sequencing (CNV-seq). Results Among 3776 pregnant women with abnormal ultrasound findings, 448 (11.86%) had chromosomal aberrations. Out of these cases, 274 (7.26%) were found to have chromosomal aneuploidies while 174 (4.61%) carried pathogenic/likely pathogenic CNVs. Moreover, our analysis established correlations between chromosomal aberrations and various phenotypic markers. Conclusion This comprehensive clinical study illuminates the pivotal role of CNV-seq in prenatal diagnosis for pregnancies featuring fetal ultrasound anomalies. [ABSTRACT FROM AUTHOR]

Differences/Disorders of sex development (DSDs) are conditions in which the development of chromosomal, gonadal, and anatomical sexes is atypical. DSDs are relatively rare, but their incidence is becoming alarmingly common in sub-Saharan Africa (SSA). Their etiologies and mechanisms are poorly understood. Therefore, we have investigated cytogenetic profiles, including telomere dysfunction, in a retrospective cohort of Senegalese DSD patients. Materials and methods: Peripheral blood lymphocytes were sampled from 35 DSD patients (mean age: 3.3 years; range 0–18 years) admitted to two hospital centers in Dakar. Peripheral blood lymphocytes from 150 healthy donors were used as a control. Conventional cytogenetics, telomere, and centromere staining followed by multiplex FISH, as well as FISH with SRY-specific probes, were employed. Results: Cytogenetic analysis identified 19 male and 13 female patients with apparently normal karyotypes, two patients with Turner syndrome, and one patient with Klinefelter syndrome. Additional structural chromosome aberrations were detected in 22% of the patients (8/35). Telomere analysis revealed a reduction in mean telomere lengths of DSD patients compared to those of healthy donors of similar age. This reduction in telomere length was associated with an increased rate of telomere aberrations (telomere loss and the formation of telomere doublets) and the presence of additional chromosomal aberrations. Conclusions: To the best of our knowledge, this study is the first to demonstrate a correlation between telomere dysfunction and DSDs. Further studies may reveal the link between telomere dysfunction and possible mechanisms involved in the disease itself, such as DNA repair deficiency or specific gene mutations. The present study demonstrates the relevance of implementing telomere analysis in prenatal tests as well as in diagnosed genetic DSD disorders. [ABSTRACT FROM AUTHOR]

Agricultural crop affected preliminary and the most prominent by the adverse effects of global climate change have to adapt to various abiotic factors that will occur as a result of climate fluctuations in the near-future and struggle to survive. Among abiotic factors, the one of the greatest impact on plant stress is high temperature. Therefore, the most important step to take action against the global threat is the development of new temperature tolerant varieties. Barley, which is the fourth most important cereal in the world after wheat, maize, and rice are affected by high ambient temperatures. In this work, the effects of their alone and in double, triple combinations of ten various plant growth regulators (PGRs) on mitotic activity and chromosome behaviors in root meristems of barley exposed to high temperature (30°C) were investigated. In the experiments, Hordeum vulgare L. cv. Bülbül 89 variety and GA3, KIN, BA, E, EBR, TRIA and PAs (Spm, Spd, Put, Cad) as growth regulators were used. The results obtained were compared with each other and with those of the seeds germinated at optimum temperature (20°C). Consequently; it has been determined that most of the PGRs studied, especially the GA3 and their combinations with GA3, exhibit a very successful performance on mitotic activity and cytogenetic aberrations in barley seeds germinated under high temperature stress- HTS conditions. The effects of these PGRs (except for EBR) and their combinations on mitotic activity and chromosome behaviors under HTS have been presented in this study for the first time.

Aging is a complex process that features a functional decline in many organelles. Various factors influence the aging process, such as chromosomal abnormalities, epigenetic changes, telomere shortening, oxidative stress, and mitochondrial dysfunction. Mitochondrial dysfunction significantly impacts aging because mitochondria regulate cellular energy, oxidative balance, and calcium levels. Mitochondrial integrity is maintained by mitophagy, which helps maintain cellular homeostasis, prevents ROS production, and protects against mtDNA damage. However, increased calcium uptake and oxidative stress can disrupt mitochondrial membrane potential and permeability, leading to the apoptotic cascade. This disruption causes increased production of free radicals, leading to oxidative modification and accumulation of mitochondrial DNA mutations, which contribute to cellular dysfunction and aging. Mitochondrial dysfunction, resulting from structural and functional changes, is linked to age-related degenerative diseases. This review focuses on mitochondrial dysfunction, its implications in aging and age-related disorders, and potential anti-aging strategies through targeting mitochondrial dysfunction.

Human exposure to radiofrequency electromagnetic fields (RF-EMF) is restricted to prevent thermal effects in the tissue. However, at very low intensity exposure ''non-thermal'' biological effects, like oxidative stress, DNA or chromosomal aberrations, etc. collectively termed genomic-instability can occur after few hours. Little is known about chronic (years long) exposure with non-thermal RF-EMF.We identified two neighboring housing estates in a rural region with residents exposed to either relatively low (control-group) or relatively high (exposed-group) RF-EMF emitted from nearby mobile phone base stations (MPBS). 24 healthy adults that lived in their homes at least for 5 years volunteered. The homes were surveyed for common types of EMF, blood samples were tested for oxidative status, transient DNA alterations, permanent chromosomal damage, and specific cancer related genetic markers, like MLL gene rearrangements. We documented possible confounders, like age, sex, nutrition, life-exposure to ionizing radiation (X-rays), occupational exposures, etc.The groups matched well, age, sex, lifestyle and occupational risk factors were similar. The years long exposure had no measurable effect on MLL gene rearrangements and c-Abl-gene transcription modification. Associated with higher exposure, we found higher levels of lipid oxidation and oxidative DNA-lesions, though not statistically significant. DNA double strand breaks, micronuclei, ring chromosomes, and acentric chromosomes were not significantly different between the groups. Chromosomal aberrations like dicentric chromosomes (p=0.007), chromatid gaps (p=0.019), chromosomal fragments (p

Background: Cascabela thevetia (L.) Lippold, a popular member of family Apocynaceae, (Yellow Oleander), being one of the preferred weapons for suicides in villages of India is grown in garden and roadside ways as a tree a. Pharmacologically active constituents include terpenoids, fla-vonoid, steroids and glycosides in seeds. Purpose: To identify the different alkaloids present in the seeds of Cascabela thevetia (L.) Lippold, and to evaluate the extent of severity of the toxic components (alkaloids) eubequitiously omnipotent in the aqueous decoction in different eukaryotic genomes. The other purpose lies in identifying this plant seed’s potency as a ready source of active but varied levels of phytochemicals that could be exploited as future “novel bioactives” as therapeutic leads in drug discovery. Results: Some important alkaloids viz., Hordenine, Ismine, Trisphaeridine, Crinine, Galanthamine, Anhydrolycorine, Assoanine, Galanthine, Incartine, Lycorine and Galwesine, are being identified in the dried seed powder of Cascabela thevetia (L.) Lippold. In addition to the presence of Carbohydrates, proteins, tannins, phenolics, terpenoids and alkaloids in the dried seed powder. The aqueous extract was found to produce significant root length inhibition in pretreated germinating Lathyrus sativus L. seeds with serially diluted concentrations (5mg, 10 mg, 20 mg, 30 mg and 40 mg/ ml respectively). There was significant occurrence of abnormal cells in the aforementioned doses of pre-treated seeds in Lathyrus sativus L., and Allium sativum L., root tip cells. There was significant induction of almost all types of clastogenic and aneugenic chromosomal aberrations. The said pre-treatments induced significant increase in nuclear budding, double nucleus, nuclear bridges, micronuclei followed by karyorrhexis and karyolysis. There was high frequency of occurrence of giant cells and apoptotic cells. At 40 mg/ml pre-treatment root tip cells there were higher degree of apoptotic responses showing nuclear fragmentations and dislodged nucleolus showing shifting on one corner of the cell in vacuolated cells. Conclusions: So it might be conclusively inferred that the seeds of Cascabela thevetia (L.) Lippold, is highly toxic for germinating plant root cells. Implications: Strict regulation and monitoring is highly needed to keep this ornamental plant from the reach of commercial cash crops including pulse crops for better safety and prevent genotoxicity.

Background: Chromosome-1 abnormalities (C1As) are common genetic aberrations in hematological malignancies. We sought to evaluate significance of these abnormalities with reference to clinical characteristics and survival outcome in a pediatric B-Lymphoblastic Leukemia (B-ALL) cohort. Methods: This is a retrospective study conducted in cytogenetic section of Indus Hospital and Health Network. Data was retrieved from October 2020 to July 2022 for childhood B-ALL cases exhibiting C1As. Chromosome analysis was performed on Cytovision MB8 using G-banded metaphases derived from unstimulated bone marrow culture. Results were recorded according to the International System for Human Cytogenetic Nomenclature (ISCN-2020). Data analyzed using SPSS, version 24.0. Results: C1As were observed in 60/450 (13.3%) cases of B-ALL. Among C1As, 29 (48%) cases had t(1;19). There were 13 (45%) balanced and 16 (55%) unbalanced translocations. The aberrations without t(1;19) were seen in 31 (52%) cases including 1q duplication with hyperdiploidy in 14 (45%) cases. The median age for C1As with and without t(1;19) was eight years and six years while the median leukocyte count was 32 x 109/L vs. 17 x 109/L. Event-free survival (EFS) for cases with and without t(1;19) was 69% and 74.2% respectively. Conclusion: Despite the fact that the t(1;19) positive group had a higher median age, a higher white cell count and more CNS positives, the difference in EFS is statistically insignificant when compared to the t(1;19) negative cases. Furthermore, we found a survival difference between balanced and unbalanced t(1;19) groups, which is statistically insignificant but warrants large-scale prospective studies for further understanding. [ABSTRACT FROM AUTHOR]

The effect of a pulsed magnetic field (PMF) on meristem cells of onion seedlings was compared with the effects of acute gamma irradiation using the allium test. It was found that a PMF with a carrier frequency of 1.8 MHz, a pulse repetition rate of 28 kHz, and a magnetic field induction of 75 mT per pulse leads to an increase in the mitotic index, mainly due to an increase in the proportion of cells in the prophase and an increase in the frequency of cells with chromosome aberrations in the ana-telophase and does not affect the frequency of cells with micronuclei. It has been suggested that a PMF causes nonspecific oxidative stress in plant cells, accompanied by a delay in the cell cycle at the check point (G2/M) and induction of DNA damage. According to these indicators, the PMF resembles the effect of ionizing radiation in doses of 0.05–0.5 Gy. [ABSTRACT FROM AUTHOR]

Introduction: Amenorrhea has been described as the cessation or absence of the menses. Two types described in the literature are primary and secondary amenorrhea (SA). Although there are known similarities in the causation for the two types of amenorrhea, the conditions warrant timed evaluation. Aims and objectives: To determine the cytogenetic abnormalities in women with amenorrhea who presented in a tertiary health care hospital, South India. Materials and methods: This was retrospective descriptive record study. Patients with amenorrhea who had presented themselves for karyotyping at St. John's Medical College and Hospital were included in the study. The study included all patients during the past 1.5 years (January 1, 2020 to June 30, 2021). Results: A total of 54 patients presented to the Division of Human Genetics for cytogenetic analysis over a period of 2.5 years with history of amenorrhea. Out of the 54 patients, 11 patients had cytogenetical abnormalities and the others had a normal karyotype. And 9 (82%) patients presented with primary amenorrhea (PA) and 2 (18%) presented with SA out of the 11 who presented with amenorrhea. The mean age of the study subjects was 22 ± 6.7 years. Peripheral blood was the specimen that was analyzed in the 11 patients. About 36% of the patients had a history of being born of a consanguineous marriage out of the 11 patients. Conclusion: This study shows the possible cytogenetic abnormalities that are present in women in a case of amenorrhea. Although most women presenting with amenorrhea have a normal karyotype, its testing remains vital for genetic counseling. [ABSTRACT FROM AUTHOR]

Radiation exposure analysis includes biological indication and biological dosimetry. Conducting such studies using human and animal cells under in vivo and in vitro conditions is not always possible or safe. The use of higher plants as test systems for assessing the impact of mutagenic factors in the environment has numerous advantages and primary bioindication of radiation exposure using them may be in great demand. Therefore, a comparative cytogenetic study of the radiosensitivity of two test systems was carried out - the plant Allium cepa and the conventional - a culture of human peripheral blood lymphocytes. An assessment was made of cytogenetic damage caused by short-term external irradiation in the range of low doses of 0.01-0.7 Gy. The presented work showed the high sensitivity of the Allium test for the induction of cytogenetic effects in the meristematic cells of onion roots. The most effective response to ionizing radiation is demonstrated by the induction of micronuclei in interphase cells. A significant positive correlation was shown between the frequency of chromosomal abnormalities in lymphocytes and micronuclei in interphase cells (+0.87), as well as the frequency of chromosomal abnormalities in metaphases of lymphocytes and onion roots (+0.93). The results obtained confirm the possibility of using the Allium cepa test system as a suitable indicator for the primary biological assessment of genotoxicity arising from external exposure to γ-radiation. [ABSTRACT FROM AUTHOR]

Cancer remains a pressing global health challenge, with millions of new cases reported annually. Oldenlandia corymbosa L. (Rubiaceae) has rich ethnomedicinal history in the treatment of various ailments. It is one of the plants used in traditional medicine for the management of cancer in Nigeria. This study aimed to assess the cytotoxic and cytogenetic potential of O. corymbosa ethanolic aerial extract (OCEE) using Allium cepa assay. The root tips of A. cepa were treated with OCEE at 1, 2, 3, 4, and 5 mg/ml for 48 hours and distilled water was used as the control. After 48 hours exposure period, cytotoxicity potential of OCEE was determined by measuring the mean length of A. cepa root compared to the control. Anti-proliferative activity of the extract was assessed by calculating the mitotic index. Cytogenetic effect of OCEE was assessed by cytological examination A cepa meristematic cells for chromosomal aberrations. The result showed a significant (p<0.05) decrease in the mean length of A. cepa root treated with OCEE (EC50 4.11 mg/ml). The mitotic index (MI) significantly reduced (p<0.05) in the lower doses, with the lowest at 1mg/ml concentration (MI = 8.50) compared to the control (MI = 9.40). The extract elicited chromosomal aberrations in all the treated groups, indicative of mutagenic and cytogenetic potential. Findings from this study showed that OCEE exerted cytotoxic, anti-proliferative and cytogenetic effect eliciting chromosomal aberrations in A. cepa root meristematic cells. The study provides insight on the use of OCEE in ethnomedicine for the management of cancer. Further research should elucidate the mechanism of action and the bioactive compounds. [ABSTRACT FROM AUTHOR]

Chromosome aberrations are an example of the mutation process that happens at the chromosome level of DNA packaging. The occurrence of inversions and complex translocations has not been studied well enough due to the complexity of their detection using the conventional methods of differential staining. It is well-known that ionizing radiation is one of the factors that increases the frequency of chromosomal rearrangements. The objective of this pilot research was to study the frequency of inversions involving telomere regions of the chromosomes and complex translocations in T-cells of 25 chronically exposed residents of the Southern Urals. Inversions were studied in the group of 12 exposed individuals (one man, 11 women, exposure doses ranging from 0.001 to 2.9 Gy) using the Q-FISH method. Complex translocations were analyzed in the group of 13 people (nine women, four men, exposure dose ranging from 0.5 to 3.1 Gy) with the help of M-FISH method. The groups did not overlap. As a result of this analysis, it has been revealed that complex translocations occur six times less frequently than simple ones (р < 0.001). Chromatid variants of inversions predominated as compared to chromosomal ones (9 : 0.17 per 100 cells, p < 0.001). No dependence of the studied parameters on the exposure dose to red bone marrow was noted. [ABSTRACT FROM AUTHOR]

Antineoplastic drugs and radioiodine are recognized occupational risk factors affecting the genetic material of exposed persons. To assess cytogenetic damage and evaluate the presence of chromosomal instability during occupational exposure, a biomonitoring study was performed using a chromosomal aberration assay and a cytokinesis-block micronucleus (CBMN) test. Blood samples from 314 healthy donors divided into 3 groups (control, exposed to antineoplastic drugs and exposed to radioiodine) were collected and cytogenetically analyzed. There was an increase in almost all analyzed parameters registered in the exposed persons. Chromatid breaks were higher in the subjects exposed to antineoplastic drugs, while dicentrics and premature centromere division (PCD) parameters were higher in nuclear medicine workers. The total number of micronuclei was higher in both groups of the exposed. The correlation analysis indicated the association of dicentrics, acentrics, chromosome and chromatid break with PCDs in both groups of the exposed, and micronuclei and nucleoplasmic bridges with PCDs in the subjects exposed to radioiodine. The discriminant analysis marked off PCD1-5 as the best predictor of exposure. Age, sex, sampling season and duration of exposure significantly influenced the analyzed parameters, while smoking habits did not show any influence. Based on the observed results, premature centromere division can be considered a valuable parameter of genotoxic risk for individuals occupationally exposed to low doses of ionizing radiation. [ABSTRACT FROM AUTHOR]

This paper presents a synthesis of silver nanoparticles by the novel method with grape pomace extract obtained by eco-friendly "green" solvent, namely, deep eutectic solvent (DES). The electrical conductivity of deep eutectic solvents was measured, and the width of electrochemical stability window was evaluated depending on water content in the solvent (0–25%). The DES was used to obtain the extract, and the latter was used in synthesis nanoparticles. The bands found in the FTIR spectrum were found to be associated with phenolic compounds. Grape pomace extract (GPE-DES) were analyzed by HPLC-DAD-MS to identify extracted compounds. The phytochemical profile of GPE-DES exhibits a high amount of the hydroxycinnamic acids (~23%), followed by anthocyanins (~19%). Furthermore, caffeic acid (164.5 μg/g), gallic acid (792.4 μg/g), and (+)-catechin (511.3 μg/g) were quantified with HPLC. A sharp absorbance peak at 436 nm was found using a UV-visible spectrophotometer, confirming the presence of AgNPs. The extensive spectroscopic study enabled the identification of synthesized AgNPs. The silver nanoparticles with round shape were noticed on the scanning electron microscopy micrographs with the particle size in the range of 10–20 nm. High antibacterial potential has been proven against gram-positive spore-forming B. subtilis and gram-negative bacteria E. coli with 9 mm and 16 mm zone inhibition, respectively, observed by agar well diffusion method. Mitotic index (MI) and chromosomal aberrations (CAs) were assessed by Allium cepa assay. The synthesized silver nanoparticles do not induce cytogenotoxic and genotoxic changes in Allium cepa L. with nanoparticles at concentration up to 10%. The silver nanoparticles are biocompatible and non-toxic. [ABSTRACT FROM AUTHOR]

In the current study, two plants, viz., Pisum sativum L. and Hordeum vulgare L., were exposed to nano- and macro-dispersed ZnO at 1, 10, and 30 times of maximal permissible concentration (MPC). The main objective of the study is to depict and compare the genotoxicity in terms of chromosomal anomalies, cytotoxicity (i.e., mitotic index), and phytotoxicity (viz., germination, morphometry, maximal quantum yield, and chlorophyll fluorescence imaging) of macro- and nano-forms of ZnO along with their accumulation and translocation. In the case of genotoxic and cytotoxic responses, the maximal effect was observed at 30 MPC, regardless of the macro- or nano-forms of ZnO. The phytotoxic observations revealed that the treatment with macro- and nano-forms of ZnO significantly affected the germination rate, germination energy, and length of roots and shoots of H. vulgare in a dose-dependent manner. The factor toxicity index of treated soil demonstrated that toxicity soared as concentrations increased and that at 30 MPC, toxicity was average and high in macro- and nano-dispersed ZnO, respectively. Furthermore, the photosynthetic parameters were observed to be negatively affected in both treatments, but the maximal effect was observed in the case of nano-dispersed form. It was noted that the mobility of nano-dispersed ZnO in the soil was higher than macro-dispersed. The increased mobility of nano-dispersed ZnO might have boosted their accumulation and translocation that subsequently led to the oxidative stress due to the accelerated production of reactive oxygen species, thus strengthen toxicity implications in plants. [ABSTRACT FROM AUTHOR]

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In this study, we investigate the toxicity of commercial formulations based on glyphosate, 2,4-D, imidacloprid, and iprodione, in isolation and mixed, on Allium cepa. The mixtures consisted of combinations in the lowest (M1), intermediate (M2), and highest concentrations (M3) of each pesticide. We measured physiological (germination rate, germination speed, and radicular length) and cyto-genotoxic (mitotic index and frequency of aberrant cells) parameters. In addition, we analyzed the cell cycle progression and cell death induction by flow cytometry. When applied in isolation, the pesticides changed the parameters evaluated. M1 and M2 inhibited root length and increased the frequency of aberrant cells. Their genotoxic effect was equivalent to that of pesticides applied in isolation. Furthermore, M1 and M2 caused cell death and M2 changed the cell cycle progression. M3 had the greatest deleterious effect on A. cepa. This mixture inhibited root length and promoted an additive or synergistic effect on the mitotic index. In addition, M3 changed all parameters analyzed by flow cytometry. This research clearly demonstrates that the pesticides tested, and their mixtures, may pose a risk to non-target organisms. [ABSTRACT FROM AUTHOR]

Introduction: In 2011, it was decided to implement chromosomal microarray in prenatal testing in the Central Denmark Region, mainly due to the expected higher diagnostic yield. Chromosomal microarray was introduced gradually for an increasing number of pregnancies and without a transition period where both karyotyping and chromosomal microarray were performed: first malformations (2011), then large nuchal translucency (2013), then high risk at combined first trimester risk screening (2016) and finally for all indications (2018). This retrospective study summarizes 11 years of using chromosomal microarray in invasive prenatal testing and presents the effect on diagnostic yield and turnaround time. Furthermore, the concerns when introducing chromosomal microarray are presented and discussed. Material and methods: Registry data from the Danish Fetal Medicine Database, the regional fetal medicine database, the Danish Cytogenetic Central Register and the local laboratory database at Department of Clinical Genetics were all combined, and a cohort of 147 158 singleton pregnancies with at least one ultrasound examination was established Results: Of the 147 158 pregnancies, invasive sampling was performed (chorionic villi or amniocytes) in 8456, corresponding to an overall invasive rate of 5.8%. Between 2016 and 2018, 3.4% (95% confidence interval [CI] 2.8–4.2%; n = 86) of the invasive samples (n = 2533) had a disease causing copy number variant and 5.3% (95% CI 4.4–6.2%; n = 133) had trisomies and other aneuploidies. The turnaround time more than halved from 14 days to an average of 5.5 days for chorionic villus sampling. Conclusions: Chromosomal microarray identified 5.3% trisomies and 3.4% copy number variants, thereby increased the diagnostic yield by more than 64% compared with karyotype only and it also more than halved the turnaround time. Some preliminary concerns proved real, eg prenatal counseling complexity, but these have been resolved over time in a clinical path with expert consultations. [ABSTRACT FROM AUTHOR]

The most sensitive biomolecule under radiation exposure is DNA, whose damage manifests itself in the form of chromosomal aberrations (CA). The processes of DNA methylation, which are involved in the regulation of gene expression, replication, DNA repair, etc., are also affected by gamma radiation. The aim of the study was to evaluate the relationship between the degree of DNA methylation and the frequency of CA after acute in vitro irradiation of human blood lymphocytes with gamma radiation. The study involved ten conditionally healthy workers of the Siberian Chemical Plant in whose blood lymphocytes the degree of methylation of CpG-dinucleotides (wide-genome bisulfite sequencing, XmaI-reduced representation bisulfite sequencing—XmaI-RRBS) and the frequency of CA (cytogenetic study) after acute in vitro irradiation of blood with doses of 0 and 1.5 Gy were evaluated. After acute exposure to gamma radiation in lymphocytes, the frequency of aberrant cells, dicentric chromosomes, and chromatid and chromosomal fragments increased. Correlation analysis of the status of CpG-dinucleotide methylation and the frequency of CA revealed changes in the degree of methylation of 97 genes, which strongly correlated positively (56 genes) or negatively (41 genes) with an increased frequency of CA. A primary genome-wide screening of genes whose methylation is correlated with a high frequency of CA was carried out. Many of the identified genes are promising as potential markers of radiation exposure and to study the mechanisms of formation of radiosensitivity of the body and radioresistance of tumors during radiation therapy. [ABSTRACT FROM AUTHOR]

The paper presents the results of evaluating the genetic and cytogenetic toxicity of etoposide, as well as the evaluation results of protective properties of aspirin against the toxicity of etoposide in C57Bl/6J mice. The cytogenetic activity and protective properties assessment was carried out using the chromosome aberration analysis in metaphase cells. Etoposide was tested at a concentration of 15 and 3 mg/kg and aspirin — at a concentration of 25 mg/kg of the animal. The results of metaphase analysis showed that etoposide exhibits cytogenetic toxicity in both doses, and aspirin exhibits protective properties against the toxicity of etoposide at a concentration of 15 mg/kg. The results of chromosome analysis regarding the protective properties of aspirin against etoposide at a concentration of 3 mg/kg are ambiguous and require further experiments.

Abstract Objective To investigate the efficiency of non-invasive prenatal testing (NIPT) in cases with different cutoffs of nuchal translucency (NT). Methods The study retrospectively analyses pregnancies with NT ≥ 2.5 mm who underwent NIPT. Results of NT, NIPT, chromosomal diagnostic and pregnancy outcomes were collected. Results Study group was composed of 1470 single pregnancies, including 864 with NT 2.5–2.9 mm, 350 with NT 3.0–3.4 mm and 256 with NT ≥ 3.5 mm. Non-significant differences were found in the positive predictive value (PPV) of NIPT between different cutoffs of NT. There was one false positive case with NT 4.3 mm, screening for 47,XYY in NIPT showed normal in diagnostic testing. For cases with normal NIPT results, the residual risk is 1:20 (5%, 95%CI: 0.1–10.1%) in fetuses with NT 3.0–3.4 mm and 1:15 (6.5%, 95%CI: 1.4%-11.5%) in fetuses with NT ≥ 3.5 mm. These false negative cases included one trisomy 21, seven pathogenic CNVs, one uniparental disomy and one single gene disorders. Conclusion Our findings demonstrated that the PPV of NIPT for screening chromosomal aberrations were similarly in different NT cutoffs, while false positive case does exist. After normal in NIPT, risk for chromosomal aberrations remained, especially pathogenic CNV and even common trisomy. Therefore, prenatal diagnosis was recommended and CMA was suggested to apply in pregnancies with NT ≥ 3.0 mm.

The analysis of cytological abnormalities is an important method for identifying the potential of a chemical as a mutagen for future heritable genetic changes, the level of genotype-mutagen interaction and site-specific activity for the nature and/or different concentrations of the mutagen. The research aims to determine the limits of the variability of genotypes of different origins, especially those with wide ecological and genetic variability, and to show the interaction between the variety and the mutagen. Winter wheat grains of several varieties (Balaton, Borovytsia, Zelenyi Hai, Zoloto Ukrainy, Kalancha, Niva Odeska, Polianka, Pochayna) were treated with dimethyl sulphate at concentrations of 0.0125%, 0.025%, 0.05%, and exposure was 24 hours. The cytogenetic activity was studied by the frequency and spectrum of chromosomal rearrangements in the corresponding phases of cell division, depending on the variety and concentration of the mutagen as the main factors affecting these parameters, as well as the main features of the spectrum, such as the overall rate of chromosomal rearrangements, the number of fragments and double fragments, bridges, micronuclei, and lagging chromosomes. The studied concentrations of the supermutagen were found to have a significant effect on all analysed parameters and can be classified as optimal and high concentration levels in terms of the effect on cytological activity and mitotic problems for the factor, despite previous studies. The variety factor has a much greater impact on the nature and frequency of certain types of aberrations than an increase in the mutagen concentration, it was characterised by a much greater site-specific effect than other chemical agents, and various variants in mutagenic effects were identified according to the subject’s genotype. It was generalised that the features that reproduced the effect of the mutagen, according to the discriminant analysis, were the total frequency, the frequency of fragments and double fragments, and bridges. In practical use in the genetic improvement of plants and for obtaining valuable traits, the optimal concentrations are 0.0125%, and 0.025%, which is planned to be further confirmed on a wider range of genotypes and by mutation studies for the next (second or third) generations

Introduction: Intramuscular myxomas are benign tumors that are challenging to diagnose, especially on core needle biopsies. Acquired chromosomal aberrations and pathogenic variants in codon 201 or codon 227 in GNAS complex locus gene (GNAS) have been reported in these tumors. Here we present our genetic findings in a series of 22 intramuscular myxomas.Materials and methods: The tumors were investigated for the presence of acquired chromosomal aberrations using G-banding and karyotyping. Pathogenic variants in codon 201 or codon 227 of GNAS were assessed using direct cycle Sanger sequencing and Ion AmpliSeq Cancer Hotspot Panel v2 methodologies.Results: Eleven tumors carried chromosomal abnormalities. Six tumors had numerical, four had structural, and one had both numerical and structural chromosomal aberrations. Gains of chromosomes 7 and 8 were the most common abnormalities being found in five and four tumors respectively. Pathogenic variants in GNAS were detected in 19 myxomas (86%) with both methodologies. The detected pathogenic variants were p.R201H in nine cases (seven with abnormal and two with normal karyotypes), p.R201C in five cases, all with normal karyotypes, p.R201S in three cases (two with abnormal and one with normal karyotype), p.R201G in one case with a normal karyotype, and p.Q227E in one case with a normal karyotype.Conclusion: Firstly, our data indicate a possible association between chromosomal abnormalities and GNAS pathogenic variants in intramuscular myxomas. Secondly, the presence of the rare pathogenic variants R201S, p.R201G and p.Q227E in 26% (5 out of 19) of myxomas with GNAS pathogenic variants shows that methodologies designed to detect only the common “hotspot” of p.R201C and p.R201H will give false negative results. Finally, a comparison between Ion AmpliSeq Cancer Hotspot Panel v2 and direct cycle Sanger sequencing showed that direct cycle Sanger sequencing provides a quick, reliable, and relatively cheap method to detect GNAS pathogenic variants, matching even the most cutting-edge sequencing methods.

Curcumin is a yellow pigment produced from the rhizomes of the Curcuma longa plant and a primary chemo preventive component of turmeric is used as a spice and food coloring ingredient. Curcumin has a large number of pharmacological activities, such as anticancer, anti-diabetic, antioxidant, anti-infectious, and anti-inflammatory properties.Investigation of the geno-protective effect of curcumin on methotrexate induces chromosomal aberrations of spleen and bone marrow cells. In this study, 32 mice were used and divided into four groups (eight mice at each group) as follows: Group1 (negative control): Dimethyl sulfoxide was given intraperitoneally to mice every day for ten days.Group2 (positive control): Mice were received a single dose (20mg/kg) of methotrexate intraperitoneally Group3: Mice were received (200mg/kg) of curcumin solution intraperitoneally for ten successive days.Group4: Mice were received (200mg/kg) of curcumin solution intraperitoneally for ten successive days and on the day 11, a single dose of methotrexate ( 20 mg/kg ) was injected intraperitoneally . In animals treated with methotrexate, significant elevations of the chromosomal aberrations were observed along with a decline in the mitotic index. Meanwhile, there was a considerable elevation of the mitotic index and no detectable chromosomal changes in the curcumin-supplemented mice. The number of abnormal cells was reduced significantly in the curcumin-treated group in comparison with the methotrexate-treated group. The ability of curcumin to inhibit methotrexate's cytotoxic effects was shown by the compound's ability to raise the mitotic index. According to this finding, curcumin approved to be a protective agent against genotoxic effects of methotrexate. Keywords: Curcumin, Chromosomal aberrations, Methotrexate, Mitotic index, Mice

Objective: To investigate the efficiency of non-invasive prenatal testing (NIPT) in cases with different cutoffs of nuchal translucency (NT). Methods: The study retrospectively analyses pregnancies with NT ≥ 2.5 mm who underwent NIPT. Results of NT, NIPT, chromosomal diagnostic and pregnancy outcomes were collected. Results: Study group was composed of 1470 single pregnancies, including 864 with NT 2.5–2.9 mm, 350 with NT 3.0–3.4 mm and 256 with NT ≥ 3.5 mm. Non-significant differences were found in the positive predictive value (PPV) of NIPT between different cutoffs of NT. There was one false positive case with NT 4.3 mm, screening for 47,XYY in NIPT showed normal in diagnostic testing. For cases with normal NIPT results, the residual risk is 1:20 (5%, 95%CI: 0.1–10.1%) in fetuses with NT 3.0–3.4 mm and 1:15 (6.5%, 95%CI: 1.4%-11.5%) in fetuses with NT ≥ 3.5 mm. These false negative cases included one trisomy 21, seven pathogenic CNVs, one uniparental disomy and one single gene disorders. Conclusion: Our findings demonstrated that the PPV of NIPT for screening chromosomal aberrations were similarly in different NT cutoffs, while false positive case does exist. After normal in NIPT, risk for chromosomal aberrations remained, especially pathogenic CNV and even common trisomy. Therefore, prenatal diagnosis was recommended and CMA was suggested to apply in pregnancies with NT ≥ 3.0 mm. [ABSTRACT FROM AUTHOR]

Chloroform is a widely used industrial chemical that can also pollute the environment. The aims of this study were to examine the potential cytotoxicity and genotoxicity of chloroform on plant cells, using the Vicia faba bioassay. Chloroform was evaluated at concentrations of 0.1, 0.5, 1, 2, and 5 mg·L−1. The following parameters were analyzed: the mitotic index (MI), micronucleus (MN) frequency, chromosomal aberration (CA) frequency, and malondialdehyde (MDA) content. The results showed that exposure to increasing concentrations of chloroform caused a decrease in MI and an increase in the frequency of MN in Vicia faba root tip cells, relative to their controls. Moreover, various types of CA, including C-mitosis, fragments, bridges, laggard chromosomes, and multipolar mitosis, were observed in the treated cells. The frequency of MN was positively correlated with the frequency of CA in exposure to 0.1–1 mg·L−1 chloroform. Furthermore, chloroform exposure induced membrane lipid peroxidation damage in the Vicia faba radicle, and a linear correlation was observed between the MDA content and the frequency of MN or CA. These findings indicated that chloroform exposure can result in oxidative stress, cytotoxicity, and genotoxicity in plant cells. [ABSTRACT FROM AUTHOR]

The current work examined the genotoxic effects of pyridaben (PDB) in male Sprague Dawley rats. Twenty Sprague Dawley rats were divided into four equal groups; the first group was used as a control group; the other three groups were exposed to 19, 28.5, and 57 mg/kg b.w PDB by oral gavage for 4 weeks. Blood samples were collected for hematological and biochemical parameters; femoral bone marrow was flushed for chromosomal aberrations (CA) assay and liver samples were used for the analysis of gene expression of IL‐6 and Casp‐3 as well as histopathological and immunhistochemical investigation for Casp‐3. The results showed that PDB exposure lead to non‐significant changes in hematological parameters in all PDB administrated groups while malondialdehyde, glutathione peroxidase, aspartate aminotransferase, and alkaline phosphatase were significantly increased in 19 and 57 mg/kg PDB doses groups Also, gene expression of IL‐6 and Casp‐3 revealed a significant increase in 28.5 and 57 mg/kg PDB doses groups as compared with the control. However, there was no significant change in the percentage of CAs in bone marrow cells in all PDB‐exposed groups. The histopathological and immunhistochemical examination showed focal areas of inflammatory cellular infiltration with fibrosis in 57 mg/kg b.w PDB dose group accompanied by the severe positive reaction of caspase3 in the liver. [ABSTRACT FROM AUTHOR]