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The highly valued oil of Rosa damascena Mill. (Rosaceae), widely used in high perfumery, cosmetics, and other spheres of human life, obliges us to know and study the safety profile of the product obtained from the water–steam distillation of fresh rose petals. The genotoxicity of the essential oil (EsO) has not been thoroughly studied despite its wide range of applications. That predetermined the object of this study—to evaluate, through classical cytogenetic methods, the possible cytotoxic/genotoxic activities of R. damascena Mill. EsO (EsORdm) in three different test systems: plant root meristem cells, mammalian bone marrow cells, and human lymphocyte cultures. The rose essential oil showed varying concentration- and time-dependent cytotoxic and genotoxic effects depending on the test system used, and it was established that the oil showed moderate cytotoxicity in lymphocyte cultures and non-high cytotoxicity in ICR mice but none in barley. Both barley and human lymphocytes showed a genotoxic effect with a dose-dependent increase in chromosomal aberrations (CAs) and a substantial rise in micronucleus (MN) frequency, while no genotoxicity was observed in bone marrow cells at the applied concentrations. Human lymphocytes exhibited the highest susceptibility to cytotoxic and genotoxic actions of the EsO. As a valuable plant-derived aromatic product with versatile uses in human life, R. damascena Mill. essential oil should be used in an appropriate concentration range tailored to cellular sensitivity. [ABSTRACT FROM AUTHOR]

Titanium dioxide (TiO2) nanoparticles are being extensively used in a wide range of industrial applications for producing a variety of different consumer products, including medicines and even food items. The consumption of these products is increasing at an alarming rate, and this results in the release of these nanoparticles in the environment, causing a threat to organisms thriving in aquatic as well as terrestrial ecosystems. That is why screening such materials for their genotoxic effects, if any, becomes essential. A toxicity assay was performed to determine the LD20 of these nanoparticles for the mosquito Culex quinquefaciatus by Probit analysis. Early fourth instar larvae were exposed to the selected dose of 50 µg/mL, which is 20 value, for 24 h treatment. Chromosomal slides were prepared from lacto-aceto-orcein-stained gonads of adult mosquitoes developed from treated and control larvae. These nanoparticles were reported cytotoxic as a statistically significant decline in mitotic index in treated mosquitoes than controls were observed. The nanoparticles were also found to induce various structural and numerical chromosomal aberrations in the treated lot. In the end, it can be concluded that these nanoparticles do have a genotoxic effect. The present study provides a caution against further use of these nanoparticles. There must be the development of strategies for the safe, sustainable use as well as proper disposal of these nanoparticles so as to protect both biotic and non-biotic components of the environment. [ABSTRACT FROM AUTHOR]

Abstract Optical genome mapping (OGM) offers high consistency in simultaneously detecting structural and copy number variants. This study aimed to retrospectively evaluate the efficacy and potential applications of OGM in preconception genetic counseling. Herein, 74 samples from 37 families were included, and their results of OGM were compared to conventional methods, namely karyotyping (KT) and chromosomal microarray analysis (CMA), which identified 27 variants across 16 positive families. Notably, OGM achieved a concordance rate of 94.7% and 100% with KT and CMA, respectively, presenting an overall concordance of 96.3%, as it missed detecting a centromeric translocation. Additionally, OGM detected two cryptic balanced translocations and a small deletion in three families that were missed by conventional methods, improving the diagnostic rate by 5.4%, along with assisting in the diagnoses of six families (16.2%) by identifying complex rearrangements and confirming cryptic translocations. The combination of KT with OGM yielded the highest diagnostic rate in all families. Overall, the findings of this study present the notable potential of OGM for its application, combined with KT per requirement, in clinical settings to improve the efficiency and accuracy of diagnoses and rapid screening of individuals seeking preconception genetic counseling.

Round cell soft tissue tumors (RCSTTs) are a diverse group of aggressive malignancies that share overlapping clinical, morphological, and immunohistochemical features, posing significant diagnostic challenges. Recent advances in molecular pathology have revolutionized the understanding and classification of these tumors by identifying tumor-specific genetic alterations. This review highlights the role of molecular insights in complementing histopathology and immunohistochemistry to achieve precise diagnosis, risk stratification, and therapeutic decision-making. Key subtypes, including Ewing sarcoma, CIC- and BCOR-rearranged sarcomas, alveolar rhabdomyosarcoma, desmoplastic small round cell tumor, and extraskeletal myxoid chondrosarcoma, are discussed with emphasis on their molecular signatures and clinical significance. The advent of techniques such as fluorescence in situ hybridization (FISH), reverse transcriptase-polymerase chain reaction (RT-PCR), and next-generation sequencing (NGS) has enabled detection of genetic fusions and aberrations critical for tumor identification and targeted therapies. Integration of molecular pathology with traditional diagnostic approaches is essential for improving diagnostic accuracy, prognostication, and therapeutic strategies, paving the way for personalized medicine in the management of RCSTTs. Full form of ABBREVIATIONS are provided at the end.

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.

Purpose of the study. Analysis of the molecular and biological features of synovial sarcoma (SS), as well as its tissue microenvironment according to modern research.Materials and methods. The analysis of literature sources was carried out mainly in the databases «Istina» and «PubMed», publication date limitations were set up from 2019 to 2023. The following keywords for the search were used: «synovial sarcoma», «chromosomal aberrations», «carcinogenesis».Results. Understanding the molecular mechanisms and signaling pathways in the development of SS may lead to the development of more effective treatment strategies. The importance of further research in this area cannot be overestimated, as it can provide new data to create innovative approaches aimed at improving the prognosis and quality of patients’ lives. Chromosomal aberrations, such as translocations and deletions, can lead to the activation of oncogenes or inactivation of tumor suppressor genes, which, in turn, contributes to the malignant transformation of cells. Epigenetic changes such as DNA methylation and histone modifications also play an important role in the regulation of genes related to the growth and survival of tumor cells. Disorders in these processes can contribute to tumor progression by altering the expression of key genes involved in the cell cycle, apoptosis, and angiogenesis. Additionally, part of the review is devoted to the interaction of atypical cells against the background of chromosomal aberrations and epigenetic changes with the SS microenvironment. These factors may have a certain effect on the growth and progression of synovial sarcoma. In addition, the review discusses various aspects of the diagnosis of SS using modern molecular genetic methods. Examples of successful use of targeted therapy and immunotherapy are given, which open up new prospects in the treatment of this disease.Conclusion. The importance of molecular biological and molecular genetic analysis of SS for the possibility of an interdisciplinary approach in the study and treatment of this aggressive malignant tumor has been revealed.

AbstractOcimum tenuiflorum, commonly referred to as holy basil or Tulsi, has a long history of use in traditional medicine systems, particularly Ayurveda, due to its various health benefits, including anti-inflammatory, antioxidant, and adaptogenic properties. In contemporary contexts, this plant is progressively incorporated into dietary supplements and nutraceuticals. Given its widespread use and potential health beneficial properties, it is imperative to scientifically evaluate the safety of Ocimum tenuiflorum. This study presents comprehensive safety assessments of a standardized extract of Ocimum tenuiflorum. We conducted a series of genotoxicity studies, including the bacterial reverse mutation test (BRMT), in-vitro mammalian chromosomal aberration (CA) test, and in-vivo mammalian erythrocyte micronucleus (MN) test in Swiss Albino mice. Additionally, an acute oral toxicity study was performed using Sprague Dawley rats, adhering to OECD guidelines in a GLP-compliant laboratory. The results showed no mutagenic effect with O. tenuiflorum extract up to a dose of 5000 µg/plate in BRMT. The results of CA test revealed the non clastogenic activity of O. tenuiflorum extract up to a dose of 500 µg/mL with and without metabolic activation (S9). Ocimum tenuiflorum extract was found to be non-clastogenic at the highest tested dose of 2000 mg/kg bodyweight in invivo MN test. In acute oral toxicity study, O. tenuiflorum extract was found to be safe up to 5 g/kg bodyweight in Wistar rats. Collectively, these findings suggest that Ocimum tenuiflorum extract is non-genotoxic and safe for oral consumption up to 5000 mg/kg body weight in Sprague Dawley rats. [ABSTRACT FROM AUTHOR]

The frequent use of electronic devices in daily lives, predominantly reliant on non-ionizing radiation, has increased the prevalence of electromagnetic radiation (EMR) in natural environment. In light of this, effects of EMR at frequencies of 1800 MHz and 2400 MHz characterized by a power of 10.0 dBm (0.01 W), across varying exposure durations of 1 h/day, 2 h/day, 4 h/day, 6 h/day, and 8 h/day for 7 days, in Allium cepa L. were studied. The effects of the treatment on the morphological features (root length, fresh weight, and dry weight of roots) and biochemical characteristics (protein content and antioxidative enzymes, namely, ascorbate peroxidase (APX), glutathione reductase (GR), superoxide dismutase (SOD), glutathione-S-transferase (GST), guaiacol peroxidase (POD), catalase (CAT), and dehydroascorbate (DHAR)) were studied in roots and bulbs of Allium cepa L. Further genotoxicity for different exposure periods at both frequencies was also conducted. Prolonged exposure to electromagnetic radiation (EMR) at both frequencies was found to reduce root length, fresh weight, and dry weight of plant. Furthermore, significant effects were observed on protein content, indicating a reduction with prolonged exposure duration. Investigation into the activities of antioxidative enzymes such as APX, GR, GST, DHAR, CAT, SOD, and POD at a frequency of 1800 MHz and 2400 MHz in roots and bulbs demonstrated a significant enhancement in enzyme activity during 6 h/day and 8 h/day exposure periods. Additional investigation during genotoxicity studies demonstrated the induction of chromosomal aberrations in the root tip cells of the Allium cepa L. plant test system. The current study revealed the initiation of oxidative stress and genotoxicity resulting from long-term exposure to electromagnetic radiation in the studied plant test systems. [ABSTRACT FROM AUTHOR]

In this study, we investigate the cytotoxic effects of the herbicides Pendinova (active ingredient Pendimethalin) and Nasa (active ingredient Glyphosate) on the root meristems of garden pea (Pisum sativum L.) variety Marci. Aqueous solutions of increasing concentrations of both herbicides were used to examine their effects on seed germination, mitotic index (MI), and chromosomal aberrations in the meristem. Results showed that the root growth of treated seeds after 72 hours varied widely and was not dependent on the concentration of the applied solutions. It was found that the herbicides Pendinova and Nasa reduce the mitotic index in a dose-dependent manner. The highest intensity of cell division was recorded in the control variant - 83.41%, indicating the mitosis-depressive effect of the herbicides on the root meristem. Plants of variety Marci responded differently to the two tested herbicides, with Nasa solutions leading to higher toxicity, most pronounced at a concentration of 3.9% with an MI of 36.2%. Chromosomal aberrations such as chromosomal stickiness, irregular metaphase and anaphase, pole deviations, lagging chromosomes and/or chromosomal fragments, and C-mitosis were described as a result of the cytotoxicity of the herbicides in the root meristem cells. [ABSTRACT FROM AUTHOR]

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]

High levels of natural radiation areas are found in different parts of the world like Yangjiang in China, Guarapari in Brazil, Ramsar in Iran and Kerala in India. These areas are considered as appropriate places for the study regarding health risks as a result of continuous exposure to elevated level of radiation, if any, on the inhabitants there. Karunagappally, lying on the south west coast of Kerala in India is known for HBR due to natural deposit of monazite sand containing thorium (8-10%), uranium (0.3%) and its decay products. The present study analysed the chromosomes in peripheral lymphocytes from the female inhabitants of HBRAs of Karunagappally and compared their results with female inhabitants of adjacent normal background radiation areas (NBRAs). Peripheral blood samples from 110 female inhabitants of HBRA of Karunagappally and 100 samples from NBRAs were collected in heparinized vials and cultures were set up employing standard microculture techniques, slides were prepared, coded and stained with giemsa. Well spreaded metaphases were analysed for chromosome aberrations. Fluoroscence in-situ hybridization (FISH) using whole chromosome probe (WCP) 1, 2, 4 and X was performed in representative samples. The frequencies of chromosomal aberrations in HBRAs and NBRAs were 5.85±3.7 and 0.27± 0.58 per hundred cells respectively. All statistical analysis were done using SPSS version 21 to assess the Group statistics in experimentals for mean age, mean cumulative dose and chromosomal aberration frequency. FISH does not reveal any translocation among the chromosomes 1, 2, 4 and X. Background radiation had effect on the frequencies of chromosomal aberration in the inhabitants of HBRA and was found significant compared to inhabitants from NBRAs. The lack of any stable aberrations/translocations in chromosomes can be considered as one of the reasons for not having any serious ill effects or increased cancer incidence due to the radiation exposure in the area. [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]

Space rockets are regularly launched from the Baikonur Cosmodrome in Kazakhstan. The ecological impact of territories affected by the consequences of space rocket activities on the environment is a significant concern. On July 27, 2006, the Dnepr rocket was launched from the Baikonur Cosmodrome, resulting in an abnormal situation and its emergency fall. The rocket fuel components, heptyl, and amyl, led to decontamination and reclamation activities. However, the self-restoration of soil and vegetation cover is currently in the earliest stages. Consequently, an assessment of the remote consequences of the accidental fall of the Dnepr launch vehicle for environmental objects was conducted. The study involved eco-toxicological characterization of habitat conditions, assessment of species diversity, determination of key morphophenetic indicators, and the genetic status of indicator species as the main parameters. The results revealed an increased level of genotoxicity in soils at the accident site. While there were deviations from the norm in some morphophenetic and cytogenetic parameters in indicator animals, they were not critical for their existence in this territory. Possibly, at the physiological level, they exhibit a high enough adaptation potential and compensatory mechanism. [ABSTRACT FROM AUTHOR]

INTRODUCTION. Metaphase analysis is used to assess the mutagenicity of medicines, and its accuracy depends directly on the quality of cytogenetic preparations. Existing procedures for cytogenetic sample preparation require optimisation because of their time and labour intensiveness and potential for artefactual chromosome loss that leads to errors in the interpretation of analytical results.AIM. This study aimed to optimise a cytogenetic sample preparation procedure for mammalian bone marrow cells for in vivo metaphase analysis.MATERIALS AND METHODS. The study was performed in randomly bred male mice weighing 18–20 g. The authors prepared cytogenetic samples of bone marrow cells according to the procedures set forth in the Guidelines for Conducting Preclinical Studies of Drugs (A.N. Mironov (ed.), 2012), and GOST 34659-2020, Methods for Testing the Impact of Chemical Products on the Human Body. Assessment of Chromosomal Aberrations in Bone Marrow Cells of Mammals, as described and with modifications. Sample preparation involved using Hanks’ solution, sodium citrate and potassium chloride solutions, acetic acid, methyl alcohol, medium 199, HEPES, and Giemsa stain.RESULTS. The authors conducted an experimental comparison of the characteristics of cytogenetic preparations of mammalian bone marrow cells for in vivo metaphase analysis prepared using several methods. The samples prepared in accordance with the Guidelines for Conducting Preclinical Studies of Drugs exhibited the highest percentage of analysable metaphase plates, in comparison with those obtained using the other sample preparation procedures. The authors optimised the sample prepara tion conditions, including the composition of the hypotonic solution (0.56% KCl), the time of hypotonic treatment (20 min), the time of fixation (12 h), and the composition of the culture medium (liquid medium 199 with Hanks’ salts and glutamine). The authors introduced a step of preliminary chromosome fixation with 6% acetic acid, which generally contributed to an increase in the proportion of analysable metaphase plates by reducing the scattering and sticking of chromosomes. CONCLUSIONS. The authors presented a modified sample preparation procedure for cytogenetic preparations that, compared with the previous procedures, offers an increase in the percentage of analysable metaphase plates to 56%, a 12% rise in the percentage of full sets of chromosomes (n=40), and a 2–10-hour reduction in the preparation time.

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.

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]

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]

Cinnamon (Cinnamomum zeylanicum) bark is used as a spice in culinary practices and has been documented for health and medicinal benefits. Polyphenol (PP) is the major bioactive constituent of cinnamon bark. However, acceptable and safe dose levels and toxicity information of oral exposure to PP-based standardized cinnamon bark extract (PP-CZ) are crucial for safe human consumption. To evaluate PP-CZ for acute oral, subchronic oral toxicities in vivo, mutagenicity in vitro and genotoxic potential in vitro. The effects of oral treatment with single- and 90-days repeated dose were evaluated in rates as per OECD Test 423 and 408, respectively. Effects on body weight, food and water intake, organ weight, hematology, biochemistry, and histology were recorded. Mutagenicity and genotoxicity were evaluated using Ames (OECD No. 471) and chromosomal aberrations (OECD Test. 473) tests. A single oral dose of PP-CZ did not cause death or treatment-related toxic effects, indicating a "median lethal dose" > 2,000 mg/ kg. In addition, a subchronic dosage (500 mg/kg/day, 90 days) was found safe in rats, suggesting "no observed adverse effect level" (NOAEL) of 500 mg/kg and "Human Equivalent Dose" (HED) of 4.8 g/day. Furthermore, the absence of mutagenicity or genotoxicity of PP-CZ was observed during in vitro tests. PP-CZ showed a robust safety profile without mutagenicity or genotoxicity in rats. [ABSTRACT FROM AUTHOR]

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]

Heliotropium keralense Sivar. & Manilal is an endangered medicinal plant native to the Indian state of Kerala. Cytotoxic effects of aqueous extracts of leaves, stems, and roots of H. keralense were evaluated using Allium cepa L. root tip method. Allium cepa bulbs were exposed to extracts of different parts of the plant for 24 hours. Compared to the negative control, a significant decrease in the length, root number and mitotic index of Allium cepa was observed with 5 to 25% aqueous extracts of H. keralense. Chromosomal abnormalities such as single, double, and multiple lesions in interphase, single and double lesions in prophase, diagonal metaphase, diagonal anaphase, bridged anaphase, strap-shaped nuclei, giant cells and chromosome loops are identified in positive control and treatments. The highest percentage of chromosomal aberration was observed in the (95.18±2.07%) positive control and 25% (71.76±7.46%) leaf extract. The analysis showed that the aqueous plant parts of H. keralense had antimitotic and cytotoxic effects. This study shows that Heliotropium keralense contains strong cytotoxic substances that can cause 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.

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.

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. [ABSTRACT FROM AUTHOR]

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]

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]

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]

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

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.

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.

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.

Titanium dioxide (TiO2) nanoparticles are being extensively used in a wide range of industrial applications for producing a variety of different consumer products, including medicines and even food items. The consumption of these products is increasing at an alarming rate, and this results in the release of these nanoparticles in the environment, causing a threat to organisms thriving in aquatic as well as terrestrial ecosystems. That is why screening such materials for their genotoxic effects, if any, becomes essential. A toxicity assay was performed to determine the LD20 of these nanoparticles for the mosquito Culex quinquefaciatus by Probit analysis. Early fourth instar larvae were exposed to the selected dose of 50 µg/mL, which is 20 value, for 24 h treatment. Chromosomal slides were prepared from lacto-aceto-orcein-stained gonads of adult mosquitoes developed from treated and control larvae. These nanoparticles were reported cytotoxic as a statistically significant decline in mitotic index in treated mosquitoes than controls were observed. The nanoparticles were also found to induce various structural and numerical chromosomal aberrations in the treated lot. In the end, it can be concluded that these nanoparticles do have a genotoxic effect. The present study provides a caution against further use of these nanoparticles. There must be the development of strategies for the safe, sustainable use as well as proper disposal of these nanoparticles so as to protect both biotic and non-biotic components of the environment.

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 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.

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

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]