Frequency Of Chromosomal Aberrations Research Articles

Protective Effect of Boric Acid Against Ochratoxin A-Induced Toxic Effects in Human Embryonal Kidney Cells (HEK293): A Study on Cytotoxic, Genotoxic, Oxidative, and Apoptotic Effects.

The present study evaluates the protective properties of boric acid (BA) against the toxic effects induced by ochratoxin A (OTA) in human embryonic kidney cells (HEK293). The focus is on various parameters such as cytotoxicity, genotoxicity, oxidative stress, and apoptosis. OTA is a known mycotoxin that has harmful effects on the liver, kidneys, brain, and nervous system. BA, on the other hand, a boron-based compound, is known for its potential as a vital micronutrient with important cellular functions. The results show that BA administration not only increases cell viability but also mitigates the cytotoxic effects of OTA. This is evidenced by a reduction in the release of lactate dehydrogenase (LDH), indicating less damage to cell membranes. In addition, BA shows efficacy in reducing genotoxic effects, as the frequency of micronucleus (MN) and chromosomal aberrations (CA) decreases significantly, suggesting a protective role against DNA damage. In addition, the study shows that treatment with BA leads to a decrease in oxidative stress markers, highlighting its potential as a therapeutic intervention against the deleterious effects of OTA. These results emphasize the need for further research into the protective mechanisms of boron, particularly BA, in combating cell damage caused by OTA.

Influence of Sayanogorsk Aluminum Plant emissions on morphological characteristics and phytopathology of Scots pine (<i>Pinus sylvestris</i> L., 1753)

This article presents data on the variability of morphological features and cytogenetic indicators in Scots Pine (Pinus sylvestris) growing in areas affected by the industrial activity of the Sayanogorsk Aluminum Plant (SAP). We demonstrated that in polluted plots located at a distance of 1 and 5 km from the plant, the reproductive organ indicators of pine significantly decreased, germination energy and viability decreased, and needle necrosis frequency increased compared with the control. A significant increase in the frequency of class III needle necrosis in experimental plots by 7.2–8.6 times compared with the control, as well as a decrease in germination energy and seed germination in experimental plots by 1.1 and 1.3–1.5 times indicates the strong negative impact of SAP emissions on pine. Mitotic index and frequency of chromosomal aberrations in the apical meristem cells of Scots Pine seedlings were determined by cytogenetic analysis. A considerable reduction in mitotic activity by 1.35 to 0.8 times was observed in the meristem cells of Scots Pine growing in experimental plots, compared with the control plot. A tendency toward an increase in the frequency of abnormal mitoses of Scots Pine in the experimental areas was observed. Thus, the data obtained made it possible to assess the condition of Scots Pine in areas exposed to the influence of SAP.

Abstract 567: Fisetin sensitizes triple negative breast cancer cells to radiation

Abstract Triple negative breast cancer (TNBC) represents a highly aggressive subtype, constituting approximately 20% of all breast cancer cases. Y-box binding protein-1 (YB-1) is often overexpressed in various tumor types and has been implicated in conferring resistance to cell death induced by radiotherapy. Fisetin, a flavonoid compound with demonstrated anti-cancer properties, operates in part through inhibiting phosphorylation of YB-1 by p90 ribosomal S6 kinase (RSK). In this study, we investigated the potential synergistic effects of combining fisetin with radiotherapy in TNBC. The activation status of the RSK signaling pathway was assessed in both total cell lysate and subcellular fractions using Western blotting. A standard clonogenic assay was employed to evaluate post-irradiation cell survival. To investigate the frequency of double-strand breaks (DSBs) and chromosomal aberrations, γH2AX foci assay and 3-color fluorescence in situ hybridization analyses were conducted, respectively. The DSB repair pathways targeted by fisetin were examined in cells expressing genomically integrated reporter constructs by quantifying green fluorescence protein expression through flow cytometry. Apoptosis and autophagy were measured using flow cytometric quantification of sub-G1 cells and the assessment of LC3-II protein expression, respectively. Kinase array and phosphoproteomics analyses were carried out to study the potential impact of fisetin on the signaling involved in the DNA damage response (DDR) after irradiation. We demonstrated that fisetin mimics the effects of RSK pharmacological inhibitors in terms of effect on YB-1 phosphorylation. Treatment with fisetin increased frequency of DSB in non-irradiated cells and impaired repair of DSB after irradiation. Fisetin attenuated DSB repair by suppressing the classical non-homologous end-joining and homologous recombination repair pathways. The frequency of chromosomal aberration was enhanced by fisetin treatment. The effect of fisetin on inhibiting DSB repair was partially YB-1 dependent. Phosphoproteomic analysis revealed that fisetin inhibits DDR signaling, which leads to radiosensitization in TNBC cells, as shown in combination with single dose or fractionated doses irradiation. Fisetin neither inhibited DSB repair nor radiosensitized normal human fibroblast HSF7 cells. The radiosensitizing effect of fisetin was not attributed to enhancing apoptosis or modulating autophagy. In summary, combining fisetin with radiotherapy may enhance TNBC radiotherapy outcomes. -This research was supported by a grant from the German Research Council (DFG,TO 685/2-3). Citation Format: Shayan Khozooei, Soundaram Veerappan, Mahmoud Toulany. Fisetin sensitizes triple negative breast cancer cells to radiation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 567.

Genetic And Environmental Associations Of Nonspecific Chromosomal Aberrations.

Nonspecific structural chromosomal aberrations (CAs) are found in around 1% of circulating lymphocytes from healthy individuals but the frequency may be higher after exposure to carcinogenic chemicals or radiation. CAs have been used in the monitoring of persons exposed to genotoxic agents and radiation. Previous studies on occupationally exposed individuals have shown associations between the frequency of CAs in peripheral blood lymphocytes and subsequent cancer risk. The cause for CA formation are believed to be unrepaired or insufficiently repaired DNA double-strand breaks or other DNA damage, and additionally telomere shortening. CAs include chromosome (CSAs) and chromatid type aberrations (CTAs). In the present review, we first describe the types of CAs, the conventional techniques used for their detection and some aspects of interpreting the results. We then focus on germline genetic variation in the frequency and type of CAs measured in a genome-wide association study (GWAS) in healthy individuals in relation to occupational and smoking-related exposure compared to non-exposed referents. The associations (at p<10-5) on 1473 healthy individuals were broadly classified in candidate genes from functional pathways related to DNA damage response/repair, including PSMA1, UBR5, RRM2B, PMS2P4, STAG3L4, BOD1, COPRS and FTO; another group included genes related to apoptosis, cell proliferation, angiogenesis and tumorigenesis, COPB1, NR2C1, COPRS, RHOT1, ITGB3, SYK, and SEMA6A; a third small group mapped to genes KLF7, SEMA5A and ITGB3 which were related to autistic traits, known to manifest frequent CAs. Dedicated studies on 153 DNA repair genes showed associations for some 30 genes, expression of which could be modified by the implicated variants. We finally point out that monitoring of CAs is so far the only method of assessing cancer risk in healthy human populations, and the use of the technology should be made more attractive by developing automated performance steps and incorporating artificial intelligence methods into the scoring.

Safety assessment of high fructose corn syrup and fructose used as sweeteners in foods

High Fructose Corn Syrup (HFCS) and Fructose (FR) are widely used sweeteners in many foods and beverages. This study aimed at investigating the cytotoxic effects of HFCS (5%–30%) and FR (62.5–2000 μg/mL) using MTT assay in Human Hepatocellular Carcinoma (HepG2) cells, and genotoxic effects of using Chromosome Aberrations (CAs), Sister Chromatid Exchanges (SCEs), Micronuclei (MN) and comet assays in human lymphocytes. HFCS significantly reduced the cell viability in HepG2 cells at between 7.5% and 30% for 24 and 48 h. 30% HFCS caused a very significant toxic effect. FR had a cytotoxic effect in HepG2 cells at all treatments. However, as fructose concentration decreased, the cell viability decreased. HFCS (10%–20%) and FR (250–2000 μg/mL) decreased the mitotic index at higher concentrations. IC50 value was found to be a 15% for 48 h. IC50 value of FR was detected as 62.5 μg/mL for 24 h and 48 h. HFCS significantly increased CAs frequency at 15% and 20%. FR significantly increased the frequency of CAs at 250, 1000, and 2000 μg/mL for 48 h. Both sweeteners increased the frequency of SCEs at all concentrations. HFCS (15% and 20%) and FR (250, 1000, and 2000 μg/mL) induced MN frequency at higher concentrations. HFCS caused DNA damage in comet assay at 10% −30%. FR increased tail intensity and moment at 125-2000 μg/mL and tail length at 62.5, 250 and 500 μg/mL. Therefore, HFCS and FR are clearly seen to be cytotoxic and genotoxic, especially at higher concentrations.

Vitamin B12 Protects Against Genotoxicity Induced by Cisplatin.

Cisplatin is an effective synthetic chemotherapeutic drug used for cancer treatment. Vitamin B12 has been shown to possess anti-genotoxic activity. This study aimed to investigate the effect of vitamin B12 on chromosomal damage induced by cisplatin. The level of sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) were measured in cultured human blood lymphocytes treated with cisplatin and/or vitamin B12. The results showed a significantly elevated frequency of CAs and SCEs of cisplatin-treated cultures compared to the control (P < 0.05). The CAs and SCEs induced by cisplatin were significantly lowered by pretreatment of cell cultures with vitamin B12. In addition, cisplatin caused a slight reduction in the mitotic index (MI), while vitamin B12 did not modulate the effect of cisplatin on MI. Vitamin B12 can protect human lymphocytes against genotoxicity associated with cisplatin.

Boron Compounds Mitigate 2,3,7,8-Tetrachlorodibenzo-p-dioxin-Induced Toxicity in Human Peripheral Blood Mononuclear Cells.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) stands as one of the most potent halogenated polycyclic hydrocarbons, known to inflict substantial cytotoxic effects on both animal and human tissues. Its widespread presence and recalcitrance make it an environmental and health concern. Efforts are being intensively channeled to uncover strategies that could mitigate the adverse health outcomes associated with TCDD exposure. In the realm of counteractive agents, boron compounds are emerging as potential candidates. These compounds, which have found applications in a spectrum of industries ranging from agriculture to pharmaceutical and cosmetic manufacturing, are known to modulate several cellular processes and enzymatic pathways. However, the dose-response relationships and protective potentials of commercially prevalent boron compounds, such as boric acid (BA), ulexite (UX), and borax (BX), have not been comprehensively studied. In our detailed investigation, when peripheral blood mononuclear cells (PBMCs) were subjected to TCDD exposure, they manifested significant cellular disruptions. This was evidenced by compromised membrane integrity, a marked reduction in antioxidant defense mechanisms, and a surge in the malondialdehyde (MDA) levels, a recognized marker for oxidative stress. On the genomic front, increased 8-OH-dG levels and chromosomal aberration (CA) frequency suggested that TCDD had the potential to cause DNA damage. Notably, our experiments have revealed that boron compounds could act as protective agents against these disruptions. They exhibited a pronounced ability to diminish the cytotoxic, genotoxic, and oxidative stress outcomes instigated by TCDD. Thus, our findings shed light on the promising role of boron compounds. In specific dosages, they may not only counteract the detrimental effects of TCDD but also serve as potential chemopreventive agents, safeguarding the cellular and genomic integrity of PBMCs.

M-FISH evaluation of chromosome aberrations to examine for historical exposure to ionising radiation due to participation at British nuclear test sites

Veterans of the British nuclear testing programme represent a population of ex-military personnel who had the potential to be exposed to ionising radiation through their participation at nuclear testing sites in the 1950s and 1960s. In the intervening years, members of this population have raised concerns about the status of their health and that of their descendants, as a consequence. Radiation dose estimates based on film badge measurements of external dose recorded at the time of the tests suggest any exposure to be limited for the majority of personnel, however, only ∼20% of personnel were monitored and no measurement for internalised exposure are on record. Here, to in-part address families concerns, we assay for chromosomal evidence of historical radiation exposure in a group of aged nuclear test (NT) veterans, using multiplex in situ hybridisation (M-FISH), for comparison with a matched group of veterans who were not present at NT sites. In total, we analysed 9379 and 7698 metaphase cells using M-FISH (24-colour karyotyping) from 48 NT and 38 control veteran samples, representing veteran servicemen from the army, Royal Airforce and Royal Navy. We observed stable and unstable simple- and complex-type chromosome aberrations in both NT and control veterans’ samples, however find no significant difference in yield of any chromosome aberration type between the two cohorts. We do observe higher average frequencies of complex chromosome aberrations in a very small subset of veterans previously identified as having a higher potential for radiation exposure, which may be indicative of internalised contamination to long-lived radionuclides from radiation fallout. By utilising recently published whole genome sequence analysis data of a sub-set of the same family groups, we examined for but found no relationship between paternal chromosome aberration burden, germline mutation frequency and self-reported concerns of adverse health in family members, suggesting that the previously reported health issues by participants in this study are unlikely to be associated with historical radiation exposure. We did observe a small number of families, representing both control and NT cohorts, showing a relationship between paternal chromosome aberrations and germline mutation sub-types which should be explored in future studies. In conclusion, we find no cytogenetic evidence of historical radiation exposure in the cohort of nuclear veterans sampled here, offering reassurance that attendance at NTs sites by the veterans sampled here, was not associated with significant levels of exposure to radiation.

Evaluation of cytotoxicity and genotoxicity of the upstream Citarum River using Allium cepa assay

Citarum River is the longest and largest river in West Java, and its existence greatly influences the lives of surrounding communities. Many industries are built around the area. It is important to assess the quality of the water, because certain heavy metal might leak to the body of water. This research aimed to investigate the mitotic index (MI), root length, frequency and types of chromosomal aberration which determined the cytotoxicity and genotoxicity by using Allium cepa L. as biomarker. The Completely randomized design with seven treatments and four replications were used. Observation was done 96 hours after onion bulb soaked in water. Data was analysed using Analysis of Variance and continued with Duncan post-hoc. Results showed that root length was not affected. Water samples were affecting the MI, frequency, and types of chromosomal aberration. The highest number of chromosome aberrations was recorded on Dayeuh Kolot stations and the most common type of aberration was stickiness. The chromosome aberrations observed were; stickiness, chromosome loss, chromosome bridge, chromosome break, binucleated cells, multipolar, micronuclei, and c-mitosis. Based on the results, Allium assay is beneficial to evaluate the level of cytotoxicity and genotoxicity in the upstream Citarum River.

Safety of GMP-compliant iPSC lines generated by Sendai virus transduction is dependent upon clone identity and sex of the donor.

Human induced pluripotent stem cells (hiPSCs) are a potential source of somatic cells for cell therapies due to their ability to self-renew and differentiate into various cells of the body. To date, the clinical application of hiPSCs has been limited due to safety issues. The present study aims to standardize the safety procedure of the derivation of GMP-compliant induced pluripotent stem cell (iPSC) lines from human fibroblasts. The hiPSC lines were generated using the nonintegrative Sendai virus method to incorporate Yamanaka reprogramming factors (OCT3/4, SOX2, KLF4 and c-MYC) into cells. A constant temperature was maintained during the cell culture, including all stages of the culture after transduction with Sendai virus. Pluripotency was proved in six independently generated hiPSC lines from adult female (47 years old) and male (57 years old) donors' derived fibroblasts via alkaline phosphatase live (ALP) staining, qPCR, and immunocytochemistry. The hiPSC lines showed a gradual decrease in the presence of the virus with each subsequent passage, and this reduction was specific to the hiPSC line. The frequency and probability of chromosomal aberrations in hiPSCs were dependent on both the iPSC clone identity and sex of the donor. In summary, the generation of hiPSC for clinical applications requires safety standards application (biosafety protocol, quality control of hiPSC lines, viral and genetic integrity screening) from the first stages of the clonal selection of hiPSC from the same donor.

Anticancer Effect of Alstonia Scholaris Against the Methyl-Methanesulphonate-Induced Genotoxicity in Human Peripheral Lymphocytes in Vitro

Abstract: Alstonia scholaris is used in various Ayurvedic preparations like Saptaparnasatvadi vati, Saptachadadi vati, Saptachhadadi vati, Saptacchadadi taila, Saptacchadadi kvatha and Saptaparna ghanasara or uses of Alstonia scholaris mainly in Whooping cough, Malaria, Jaundice, Gastric complaint, Headache, Asthma, Stomachache, Wound, Fever and also much effective in all types of cancer. The antigenotoxic potential of Alstonia scholaris extract (AS) was demonstrated on the methyl methanesulphonate (MMS) induced genotoxicity. In vitro studies were carried on human lymphocyte culture. We have used chromosomal aberration (CA), sister chromatid exchange (SCE) and cell cycle kinetics (CCK) with and without S9 mix. as markers in this experiments. Four doses viz., 100, 150, 200, 250 μl/ml per culture were selected and found that Alstonia scholaris extract significantly reduces the frequencies of chromosomal aberration, sister chromatid exchanges and enhances RI in vitro .It was also noticed that the antigenotoxic potential of AS shows dose – response relationship. The results suggest that AS was a potent anticarcinogen may contribute to the cancer prevention.

Cytogenetic analysis of coke oven workers in Eastern Slovakia.

Our study aimed to evaluate the extent of polycyclic aromatic hydrocarbon (PAH) exposure in coke oven workers from Eastern Slovakia by cytogenetic analysis of human peripheral lymphocytes. A total of 81 peripheral blood samples were collected from PAH-exposed workers (mean age 45.84 ± 9.73 years) and 30 samples constituted the control group (41.93 ± 15.39 years). The samples were processed using routine cytological analysis. Conventional cytogenetic analysis of human peripheral lymphocytes has been used to evaluate the effects of PAHs. Comparison of the aberrant cells in the total exposed with the controls showed a significant difference (p < 0.05). A high level of significance (p < 0.001) was observed when comparing the gaps between the exposed group and the control group. There was a significant difference (p < 0.01) in aberrant cells and chromatid breaks (p < 0.05) in the GR1 working subgroup compared with the control group. The results of the correlation analysis did not show a significant relationship between the length of occupational exposure and the frequency of aberrant cells (r = 0.071, p = 0.529). Similarly, no association was observed between smoking among coke plant workers and the frequency of aberrant cells (r = 0.117, p = 0.538). Cytogenetic analysis showed an increased frequency of chromosomal aberrations in coke oven workers in Eastern Slovakia.

A retrospective analysis of spontaneous chromosomal aberrations in human lymphocyte cultures of individuals from Bosnia and Herzegovina

Spontaneous chromosomal aberrations are structural or numerical changes of chromosomes that occur naturally, without exposure to external genotoxic factors. They are not inherited, occur randomly in the karyotype, and do not have direct clinical significance. However, they can affect genomic instability and disease predisposition. They can result from DNA replication or repair processes errors, and typically are observed in cells that are actively dividing. Spontaneous chromosomal aberrations may arise due to the natural chromosomal instability and can be elevated in individuals exposed to mutagens. We analyzed frequencies of spontaneous chromosomal aberrations in 137 individuals subjected to karyotype analysis at the Laboratory for Cytogenetics and Genotoxicology, University of Sarajevo – Institute for Genetic Engineering and Biotechnology, during 2008-2023. Whole blood samples were cultivated for 72 hours with the thymidine added in the 48th hour. Metaphases were arrested by colcemid 60 minutes before harvesting. GTG banding was performed and slides were analyzed under 1000x magnification in accordance with An International System for Human Cytogenetic Nomenclature and E.C.A. Cytogenetic Guidelines and Quality Assurance. Constitutionally aberrant karyotypes were found in 2.92% of analysed individuals as well as altered karyotypes considered as normal chromosomal variants. In the total of 3092 analyzed metaphases, 20 spontaneous chromosomal aberrations were found in 13 individuals. This study contributes to the limited knowledge of the cytogenetic status of the Bosnian and Herzegovinian population. Further monitoring of spontaneous chromosomal aberrations incidences is recommended.

Palmitoyl ascorbic acid glucoside enhanced cell survival with post irradiation treatment

Radiation exposure poses a significant threat to cellular integrity by inducing DNA damage through the generation of free radicals and reactive oxygen species. Ascorbic acid, particularly its derivative Palmitoyl Ascorbic Acid 2-Glucoside (PA2G), has demonstrated remarkable radioprotective properties. While previous research focused on its pre-irradiation application, this study explores the post-irradiation radiomitigation potential of PA2G. Our findings reveal that post-irradiation treatment with PA2G enhances cell survival and accelerates DNA repair processes, particularly the non-homologous end-joining (NHEJ) repair pathway. Notably, PA2G treatment reduces the frequency of lethal chromosomal aberrations and micronuclei formation, indicating its ability to enhance the repair of complex DNA lesions. Furthermore, PA2G is shown to play a role in potentially lethal damage repair (PLDR). These radioprotective effects are specific to NHEJ and ATM pathways, as cells deficient in these mechanisms do not benefit from PA2G treatment. This study highlights PA2G as a versatile radioprotector, both pre- and post-irradiation, with significant potential for applications in radiation therapy and protection, offering new insights into its mechanism of action. Further research is required to elucidate the precise molecular mechanisms underlying PA2G's radiomitigation effects and its potential clinical applications.

The study of the impact of additional chromosomal aberrations and c-MYC and BCR::ABL1 genes amplification on CML patient’s characteristics: relation to haematological parameters and patient outcome

BackgroundChronic myeloid leukaemia is characterised by genetic instability which results in additional cytogenetic aberrations that have been linked to progression to advanced phase. Genomic study linked amplified genes in the form of c-MYC and/or the rare BCR::ABL1 genes amplification to chronic myeloid leukaemia. The effect of these genes’ amplification on patients’ characteristics and disease progression still needs further study.This cross-sectional study aimed to investigate the frequency of additional chromosomal aberrations in addition to c-MYC and BCR::ABL1 genes amplification in chronic myeloid leukaemia patients and their impact on patient’s characteristics, disease progression, and level of remission. The study included cytogenetic analysis of 49 Philadelphia positive chronic myeloid leukaemia patients and investigation of c-MYC and BCR::ABL1 genes amplification by fluorescence in situ hybridization.ResultsPatients with additional chromosomal aberrations represented 36.7% and had significantly lower platelet count (P = 0.003) and higher blast count (P = 0.008). The acquisition of additional chromosomal aberrations was significantly higher in chronic myeloid leukaemia patients with advanced stages (P = 0.014). Follow-up of the patients for 6 months revealed significant higher frequency of additional chromosomal aberrations in patients with failure of remission (P < 0.0001). A highly significant association between cases with failure of molecular remission (P = 0.001) and co-existing additional chromosomal aberrations.Amplification of the c-MYC gene was detected in 6 cases. The cases with c-MYC amplification showed significantly higher peripheral blood and bone marrow blasts (P = 0.029 and P = 0.008, respectively) and significantly lower platelet count (P = 0.044). Amplification of c-MYC was significantly associated with additional chromosomal aberrations (P = 0.011). Molecular remission was not achieved in any of the instances with c-MYC amplification. A highly significant association between c-MYC amplification and poor patient outcome was detected (P = 0.002). BCR::ABL1 amplification was detected in three cases, and ABL amplification was detected in four cases. Patients with BCR::ABL1 amplification showed significantly higher blast count. BCR::ABL1 amplification was significantly associated with disease progression and failure of molecular remission (P = 0.002).ConclusionAdditional chromosomal aberrations, c-MYC amplification, and BCR:ABL1 amplification in chronic myeloid leukaemia stratify patients with disease progression, which may lead to better interventions and improved outcome in the future chronic myeloid leukaemia patients.

Detection of chromosome aberrations in 17 054 individuals with fertility problems and their subsequent assisted reproductive technology treatments in Central China.

How do the types and frequency of chromosome aberrations in couples in central China affect fertility and ART treatment? Men with chromosome aberrations or polymorphisms have an increased risk of semen quality impairment and infertility, and couples affected by reciprocal translocations had a lower pregnancy rate compared with other chromosome aberrations. Karyotyping is crucial for patients affected by infertility as chromosome aberrations play an important role in the etiology of male infertility. However, the influence of chromosome aberrations and polymorphisms on sperm motility and morphology remains controversial. Data on ART treatment outcomes in infertile couples affected by chromosome aberrations are insufficient. We conducted a retrospective study involving 17 054 patients affected by infertility who underwent karyotyping in our center between January 2020 and May 2022. Karyotyping was performed on 17 054 patients with reproductive failure. All patients were from the central regions of China. The following data were collected from a medical records system using patient identification numbers: couples' ages, history of pregnancy and childbirth, type of infertility, years of infertility, cause of infertility, chromosome karyotypes, semen analysis results, assisted reproductive techniques performed, and treatment outcomes of ART. The incidence of chromosome aberrations was 2.04%; 2.49% in men and 1.57% in women. By analyzing the relationships between chromosome aberrations/polymorphisms and abnormal semen parameters, we found that there were significantly higher rates of asthenozoospermia, oligospermia, and teratozoospermia among men with Robertsonian translocations and sex chromosomal structural aberrations compared with those with normal karyotypes. Higher rates of asthenozoospermia and teratozoospermia were also observed among men with autosomal reciprocal translocations. The incidence of chromosome aberrations in azoospermic men (13.75%), and in men with cryptozoospermia or severe oligospermia (6.97%) was significantly higher than that in men with mild oligospermia or normospermia (0.88-2.12%). In addition, we found that the progressive movement of sperm is impaired in men with Chromosome 21 polymorphisms compared with men with normal karyotypes (39.46% ± 20.51% vs 48.61% ± 18.76%, P = 0.026). The percentage of morphologically normal forms was lower in the chromosomal polymorphism group than in the normal karyotype group (5.01% ± 2.41% vs 5.59% ± 2.14%, P = 0.001), especially in men with polymorphisms on Chromosome 9 (enlarged Chromosome 9 heterochromatin [9qh+]: 4.48% ± 2.22% vs 5.59% ± 2.14%, P = 0.006; pericentric inversion of Chromosome 9 [inv(9)]: 5.09% ± 3.11% vs 5.59% ± 2.14%, P = 0.008). ART treatment was successful in 36.00% of couples affected by chromosome aberrations. However, couples affected by reciprocal translocations achieved a lower pregnancy rate (24.07%), which may be due to the lower euploidy rates (27.31%) when compared with that in other chromosome aberrations. First, although the initial cohort was large, chromosome aberrations were identified in a small number of patients. Second, the observational nature of the study design is limiting. Third, the couples affected by infertility in this study were all outpatients that did not undergo identical comprehensive examinations except for karyotyping, leading to the incomplete collection of medical records. Also, the population included in this study mainly focused on couples affected by infertility, which may not be included in the European Association of Urology (EAU) recommendation on male infertility. Men with chromosome aberrations or polymorphisms have an increased risk of semen quality impairment and infertility. Constitutional chromosome analysis is recommended for men affected by infertility and severe oligospermia or azoospermia to facilitate early and appropriate guidance for the most suitable treatment. Carriers of chromosome aberrations can achieve acceptable pregnancy outcomes through IVF. However, couples affected by reciprocal translocations have lower pregnancy rates, and more treatment cycles are needed before a successful pregnancy. A possible explanation may be the fewer euploid embryos obtained. This work was supported by Grant 2021YFC2700603 from the National Key Research & Development Program of China. The authors declare no conflicts of interest. N/A.

Assessing the Association of the Degree of DNA Methylation and the Frequency of Chromosomal Aberrations in Human Lymphocytes in a Single Irradiation of Blood &lt;i&gt;in vitro&lt;/i&gt;

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 10 conditionally healthy workers of the Siberian Chemical Combine, 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 blood irradiation 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, 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 correlates 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.

Assessing the Association of the Degree of DNA Methylation and the Frequency of Chromosomal Aberrations in Human Lymphocytes in a Single Irradiation of Blood In Vitro

Assessing the Association of the Degree of DNA Methylation and the Frequency of Chromosomal Aberrations in Human Lymphocytes in a Single Irradiation of Blood In Vitro

Determination of the genotoxic effects of sweeteners, mannitol and lactitol

The changes in dietary habit around the world have led to an increased use of additives in the food. The safety of food additives has been a main focus of research for many years due to the ongoing debate on their potential effects on health. In this study, the in vitro genotoxic effects of mannitol and lactitol, polyols used as sweetener food additives, were evaluated using chromosomal aberrations (CAs) and micronucleus (MN) assays in human peripheral lymphocytes. Additionally, the effects of these sweeteners on the mitotic index (MI) and nuclear division index (NDI) were investigated. Concentrations of 500, 1000, 2000, 4000, and 8000 μg/mL for mannitol and 250, 500, 1000, 2000, and 4000 μg/mL for lactitol were used. The results indicated that both polyols did not affect CA and MN frequency, and did not cause a significant change in NDI at all treatment concentratoins. However, mannitol (except at concentrations of 500 and 1000 μg/mL) and lactitol (except at 250 μg/mL) significantly decreased the MI compared to the control at almost all concentrations and treatment times. In conclusion, it was observed that mannitol and lactitol did not have a significant genotoxic effect at the concentrations used in human lymphocytes in vitro.

CYTOTOXIC AND GENOTOXIC EFFECTS OF UV IRRADIATION ON ROOT MERISTEM CELLS OF ALLIUM CEPA L

The widespread use of ultraviolet radiation as a disinfectant necessitates an investigation into its possible harmful effects in living organisms. In the present study the effect of exposure to UVC radiation was studied using the Allium cepa assay. To determine the effect of UVC radiation, roots of four sets of A. cepa bulbs were irradiated with 254 nm UV radiation for durations of half, one, two and four hours, respectively. The cytotoxicity of UVC radiation was assessed by comparing the mitotic index of root meristem cells of exposed roots and unirradiated roots (control). Frequency of chromosomal aberrations in the dividing cells of the root meristem was taken as a measure of the genotoxicity of UVC radiation. The roots subjected to UVC exposure showed several types of chromosomal aberrations including sticky chromosomes, c-metaphase, vagrant chromosomes, irregular anaphase, multipolar anaphase, chromosomal bridges and laggards. The study clearly shows that exposure to UVC radiation for even a brief period of half an hour is cytotoxic and genotoxic.