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Eutrophication is one of the environmental problems arising from the increase of essential nutrient concentrations, mainly phosphorus and nitrogen. In contrast to excess phosphorus, the depletion of phosphate rock deposits used for the production of fertilizers compromises the food supply. Therefore, the development of technologies that propose the recovery of the phosphorus contained in eutrophic environments for its later use for agricultural fertilization purposes is very important to ensure global food security. This work aimed to evaluate the toxic potential of the sawdust (biosorbent previously used for phosphorus adsorption) in order to enable its application in agriculture. For this, toxicity experiments with Lactuca sativa (lettuce) and Allium cepa (onion) seeds were performed. The phytotoxic potential was assessed by means of the seed germination index and physiological parameters such as radicle and hypocotyl growth. Cytotoxicity, genotoxicity, and mutagenicity tests were also performed on onion seeds. From statistical tests, it was possible to affirm that the sawdust did not promote inhibition of seed germination and radicle and hypocotyl growth. No genotoxicity, cytotoxicity and, mutagenicity were observed, which allowed to state that the sawdust is not toxic to the onion species, which reinforces the possibility of application of the biosorbent for soil fertilization purposes. Therefore, the use of sawdust for phosphorus biosorption with the subsequent agricultural application is promising and quite important from a global food security point of view. [ABSTRACT FROM AUTHOR]

Background: Given the prognostic importance of cytogenetic aberrations in plasma cell neoplasms, the present retrospective study was conducted to analyze cytogenetic abnormalities in plasma cell myeloma cases in a single center in the Middle East. Method: In this retrospective cross-sectional study, we selected 42 patients referred to the molecular and cytogenetic department from 2013 to 2016 for initial assessment by immunohistochemical, flow cytometric, and cytogenetic studies. Chromosomal analysis was performed after a 72-hour unsynchronized culture and Giemsa banding; the result was reported according to ISCN 2016. Results: 32.5% of the patients showed an abnormal karyotype, of whom 53.8% were hyperdiploid and the rest were assigned to the non-hyperdiploid group. The gain of 1q and monosomy 13/ deletion 13q were the most common structural abnormalities accounting for 38.4% and 30.7%, respectively. t(11;14) was the only detected 14q32 rearrangement observed in 15.4% of the cases. The mean survival time in normal, hyperdiploid, and non-hyperdiploid groups was 29.5±1.7, 16.6±2.9 and 6.1±2.1 months, respectively. Conclusion: Cytogenetic abnormalities of plasma cell myeloma in this center were relatively similar to previous reports in the literature; moreover, hyperdiploidy was the most common cytogenetic aberration. As no cryptic aberration could be identified, we recommend the use of more precise techniques such as FISH in addition to conventional G banding to detect cryptic aberrations. Survival of the non-hyperdiploid group was the worst. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to evaluate the DNA and chromosomal damage in peripheral blood lymphocytes (PBLs) of patients with acute coronary syndrome (ACS) and to explore the effect of coronary angiographies in these patients. Methods: The study included ACS patients who underwent a coronary angiography (CAG) and healthy controls. The ACS sample was divided into two groups: patients with unstable angina pectoris (UAP) and acute myocardial infarction (AMI). The frequency of DNA damage [expressed as genetic damage index (GDI)] was analyzed using the comet assay pre- and post-CAG. Chromosomal aberrations were measured as micronuclei (MNs) frequency using the cytokinesis-block MN (CBMN) assay. Additionally, detailed anamnestic data were taken from the each patient. Results: Increased levels of DNA and chromosomal damage have been revealed in ACS patients compared to the healthy controls. GDI values were also significantly higher in AMI patients than in UAP patients. A highly significant increase of DNA damage was also observed in all patients post-CAG. There was significantly higher MN frequency and significantly lower nuclear division index (NDI) in AMI patients than in UAP patients' pre-CAG. After CAG, there was no significant difference in MN frequencies and NDI values between UAP and AMI patients. Conclusion: Correlated with disease severity, our results showed that AMI patients have higher levels of both DNA and chromosomal damage in PBLs compared to UAP patients. The increased level of genome instability was especially evident post-CAG compared to the observed damage pre-CAG. [ABSTRACT FROM AUTHOR]

The current study was investigated the genotoxic effects of levofloxacin on bone marrow stem cells of mice before and after infection with uropathogenic E. coli by depended on the calculation of cell number and Mitotic index. The experiment was carried out in Al-Qasim Green, Veterinary Medline College during 2019-2020. (40) Adult mice were used in the study. E. coli were provided from Bacteriology Laboratory in Babylon Province. The isolates were examined and identity biochemically and showed positive results for E.coli and one isolate was selected for making this experiment. The isolate was submitted to intermediate sensitivity to levofloxacin, which showed an inhibition zone of (16) mm. The study consist of four groups of mice, each group consists of (10) animals, divided as follows: the control group (G1) injected (0.25) ml normal saline every (8) hour for (48) hours, (G2) injected with levofloxacin every (8) hour for (48) hours, (G3) injected for (48) hours with (0.1) ml of E. coli, (G4) injected with levofloxacin every (8) hour for (5) days. The used test in our study is included a mitotic index for determining the genotoxicity effect of levofloxacin. Our finding showed that the Control Group showed that divided cells at metaphase were (652) cell and Mitotic Index was (11.58%). Also, the (G2) showed that a number of dividing cells in metaphase was (529) out of (8000) cells and Mitotic Index was (11.58%), (G3) showed a number of dividing cells in metaphase were (507) cells out of (8000) cells and Mitotic Index was (7.14) % at (p ≤ 0.05). (G4) showed that the number of dividing cells in metaphase was (629) and Mitotic Index was (10.74%). In conclusion, the (G2) and (G3) showed decrease significant differences as compared with the control groupat (P≤ 0.05), while (G4) showed increase significant differences as compared with (G2) and (G3) at (P≤ 0.05). However, don't show significant differences as compared with the control group at (P≤ 0.05) [ABSTRACT FROM AUTHOR]

TP53 (p53) is a pivotal player in tumor suppression with fifty percent of all invasive tumors displaying mutations in the TP53 gene. In the present study, we characterized colon cancer cells (HCT116 p53 −/−) with TP53 deletion, a sub-line derived from HCT116-p53 +/+ cells. RNA sequencing and network analyses were performed to identify novel drug resistance mechanisms. Chromosomal aberrations were identified by multicolor fluorescence in situ hybridization (mFISH) and array comparative genomic hybridization (aCGH). Numerous genes were overexpressed in HCT116 p53 −/− cells: RND3/RhoE (235.6-fold up-regulated), DCLK1 (60.2-fold up-regulated), LBH (31.9-fold up-regulated), MYB (28.9-fold up-regulated), TACSTD2 (110.1-fold down-regulated), NRIP1 (81.5-fold down-regulated) and HLA-DMB (69.7-fold down-regulated) are among the identified genes with potential influence on multidrug resistance (MDR) and they are associated with cancer progression and tumorigenesis, according to previously published studies. Probably due to TP53 deletion, disturbances in DNA repair and apoptosis are leading to aberrancies in cellular and organismal organization, ultimately increasing tumorigenesis and cancer progression potential. With NFκB, PI3K and HSP70, being at the center of merged protein network, and TH1-2 pathways, being among the influenced pathways, it can be speculated that the inflammatory pathway contributes to a resistance phenotype together with cell cycle regulation and heat-shock response. HCT116-p53 −/− cells have more chromosomal aberrations, gains and losses in copy numbers than HCT116-p53 +/+ cells. In conclusion, numerous genomic aberrations, which might be associated with yet unknown drug resistance mechanisms, were identified. This may have important implications for future treatment strategies. [ABSTRACT FROM AUTHOR]

Per‐ and polyfluoroalkyl substances (PFAS) have emerged as contaminants of global concern. Among several PFAS, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are persistent and bioaccumulative compounds. We investigated the cyto‐genotoxic potential of PFOS to Allium cepa root meristem cells. The A. cepa root tips were exposed to 6 different concentrations (1–100 mg L−1) of PFOS for 48 h. Reduction in mitotic index and chromosomal aberrations was measured as genotoxic endpoints in meristematic root cells. Exposure to PFOS significantly affected cell division by reducing the miotic index at higher concentrations (>10 mg L−1). The median effect concentration of PFOS to elicit cytotoxicity based on the mitotic index was 43.2 mg L−1. Exposure to PFOS significantly increased chromosomal aberrations at concentrations >25 mg L−1. The common aberrations were micronuclei, vagrant cells, and multipolar anaphase. The alkaline comet assay revealed a genotoxic potential of PFOS with increased tail DNA percentage at concentrations >25 mg L−1. To our knowledge, this is the first study to report the cyto‐genotoxic potential of PFOS in higher plants. Environ Toxicol Chem 2021;40:792–798. © 2020 SETAC [ABSTRACT FROM AUTHOR]

Introduction: Duplication of the renal collecting system is one of the most common variants of urinary tract anatomy. The objective of our study was to examine the risk for chromosomal aberrations in this isolated prenatal sonographic finding. Methods: Data from all chromosomal microarray analyses (CMA) reported to the Ministry of Health between January 2013 and September 2017 were retrospectively obtained from a computerized database. All pregnancies with a sonographic diagnosis of the isolated duplex renal collecting system and documentation of CMA result were included. Rate of abnormal CMA findings was compared to the general population risk, based on a systematic review encompassing 9272 cases with normal ultrasound and a local data of 5541 pregnancies undergoing CMA due to maternal request. Results: Two pathogenic CMA finding was found amongst 143 pregnancies with double collecting system (1.4%), not significantly different from the risk for abnormal CMA results in the general population. In addition, five variants of unknown significance were demonstrated (3.5%). Conclusion: To our best knowledge, this analysis is the first report describing the rate of chromosomal anomalies in pregnancies with isolated duplex renal collecting system. Its results suggest that routine invasive prenatal testing with CMA analysis in such cases is no more useful than in the general population. Prospective well-adjusted studies are needed to guide the optimal management of these pregnancies. [ABSTRACT FROM AUTHOR]

The application of pesticides to get more agricultural products is increasing day by day. The use of a huge amount of pesticides raises public concerns about safety. Tetraconazole is a widely used and successful fungicide. Possible toxic, cytotoxic, and genotoxic effects of different doses of tetraconazole (1.00 mg/L, 5.00 mg/L, and 10.00 mg/L) were evaluated on the meristematic cells of Allium cepa L. root tips by means of physiological, cytogenetic, biochemical, and anatomical parameters. EC50 value for tetraconazole in terms of growth inhibition was calculated as 6.7 mg/L. Increasing doses of tetraconazole resulted in reduced germination ratio, root length, and weight gain. Total activities of superoxide dismutase (SOD) and catalase (CAT) enzymes as well as malondialdehyde (MDA) content were increased as a result of oxidative stress. As an evidence of genotoxicity, mitotic index (MI) level decreased, while scores for micronucleus (MN) and chromosomal aberrations (CAs) rose. In addition, various meristematic cell damages were detected in root tips of tetraconazole applied bulbs. As a result, the multiple toxic, cytotoxic, and genotoxic effects of tetraconazole fungicide were demonstrated through a wide range of parameters on A. cepa, which was found to be a versatile tool for testing hazardous pesticides. [ABSTRACT FROM AUTHOR]

The Itapemirim River is considered one of the most important water resources in the state of Espírito Santo, Brazil. However, environmental problems due to continuous anthropogenic contamination are threatening its potential use. This study assessed water quality by analyzing abiotic and toxicogenetic aspects of the water from four stations along the river. Samples were collected in both dry and rainy seasons. Most of the abiotic variables were below the threshold established by CONAMA Resolution No. 357/2005, and so were most of the metals. However, Al and Cu contents were above those allowed by legislation, ranging from 0.2 to 0.9 mg/L. Regarding toxicogenetic aspects, genotoxic effects were observed in meristematic cells of Allium cepa, in micronucleus test and comet assay of Oreochromis niloticus, and CHO-K1 cells. Mutagenic effects were significant at RI 02 (0.34), RI 03 (0.46), and RI 04 (0.12) stations on the first campaign in A. cepa F1 cells, compared to the negative control (0.0). The second campaign revealed the same results, but with the addition of samples from RI 01 (0.17) and RI 03 (0.18) showing mutagenicity in the micronucleus test with fish erythrocytes when compared to the negative control (0.3). Essentially, all the samples evaluated in both campaigns showed damage in A. cepa, O. niloticus, and CHO-K1 cells, thus demonstrating that the water quality of the Itapemirim River is compromised and requires action plans for its recovery. [ABSTRACT FROM AUTHOR]

In this study, the cytotoxic potential of fluoride and endosulfan in combination was investigated in Swiss albino mice bone marrow cells using the chromosomal aberration (CA) and micronucleus (MN) test systems. Fluoride (25.1 mg kg-1 body weight [bw] in water) and endosulfan (1.8 mg kg-1 bw by oral intubation) were administered orally alone and in combination (fluoride 25.1 mg kg-1 bw þ endosulfan 1.8 mg kg-1 bw) to male Swiss albino mice daily for 30 days. A significant (p < 0.01) increase in micronuclei (MNs) induction and decreased ratio (p < 0.01) of polychromatic to normonochromatic erythrocytes (indicators of cytotoxicity) were observed compared with saline controls when animals were given the combination of fluoride and endosulfan. A significant (p < 0.01) increase in MNs induction and no change in the polychromatic erythrocytes to erythrocyte ratio were also observed when endosulfan was given alone. CAs such as gaps, breaks, fragments, rings, exchanges, and polyploidy were recorded in the bone marrow cells. The mean percent frequency of CAs was increased (p < 0.01) in all the treated groups compared with the control saline group. In the combination group (F þ E), the percent frequencies of CAs were significantly higher (13.875%) compared with those in the individual treatment groups of fluoride (4.375%) and endosulfan (6.25%). The mitotic index was calculated as percentage of dividing cells. A significant (p < 0.01) decrease in mitotic index was observed in all treated groups compared with controls. In the combination group (F þ E), mitotic index was significantly less than (p < 0.01; 4.1 + 0.49) the saline control (10.8 + 0.98). These results indicated that repeated intake of endosulfan through various sources in fluoride affected areas resulted in increased cytotoxic effects. The greater effect in the combination group indicated additive interaction of fluoride and endosulfan in inducing cytotoxicity in Swiss albino mice. [ABSTRACT FROM AUTHOR]

Chromosomal aberrations (CAs) are an important tool for assessment of exposure to pesticides. Genotoxic potential of pesticides is a principal risk factor for long‐term health effects. The present study was aimed toward the assessment of CAs among agricultural workers exposed to pesticides and comparison with nonagricultural workers not exposed to pesticides. A total of 296 subjects were enrolled in the study: exposed (n = 148) and nonexposed subjects (n = 148) from Punjab. A significantly high frequency of aberrations was seen in peripheral blood lymphocytes of exposed subjects as compared with nonexposed ones. Most CAs were present as loss (aneuploidy) and were observed significantly in subjects having a history of alcohol consumption. It can be, thus, concluded that agricultural workers exposed to a mixture of pesticides, in addition to being alcoholic, are at a greater risk of genotoxic damage. It is highly recommended that the agricultural workers are educated regarding the potential hazards of occupational exposure to pesticides. [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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Somasundaram, Jain, Blot-Chabaud, Pathak, Banerjee, Rawat, Sharma and Duttaroy.)

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., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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 < 0.0001) and similarly there was significant elevation in the estrogen levels found in 7th week endosulfan treated mice. It also influenced the level of free radicals as there was significant decrease (p < 0.0001) in the value in catalase levels in 7 weeks endosulfan treated male and female mice, while significant (p < 0.0001) increase in the values of lipid peroxidation levels as 8 folds and 10 folds in 7 weeks endosulfan treated male and female Swiss albino mice respectively. This study hence speculates that the endosulfan exposed population are at the risk of reproductive health hazards., Conclusions: The present study thus concludes that, endosulfan after 7 weeks of exposure caused significant reproductive damage to both male and female Swiss albino mice groups. Moreover, the karyotyping study also correlated the genotoxic damage in the mice., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

Topotecan administered intraperitoneally at single doses of 0.25, 0.5, and 1 mg/kg induced chromosomal aberrations in bone marrow cells of F 1 (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., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Undesired on- and off-target effects of CRISPR-Cas nucleases remain a challenge in genome editing. While the use of Cas9 nickases has been shown to minimize off-target mutagenesis, their use in therapeutic genome editing has been hampered by a lack of efficacy. To overcome this limitation, we and others have developed double-nickase-based strategies to generate staggered DNA double-strand breaks to mediate gene disruption or gene correction with high efficiency. However, the impact of paired single-strand nicks on genome integrity has remained largely unexplored. Here, we developed a novel CAST-seq pipeline, dual CAST, to characterize chromosomal aberrations induced by paired CRISPR-Cas9 nickases at three different loci in primary keratinocytes derived from patients with epidermolysis bullosa. While targeting COL7A1, COL17A1, or LAMA3 with Cas9 nucleases caused previously undescribed chromosomal rearrangements, no chromosomal translocations were detected following paired-nickase editing. While the double-nicking strategy induced large deletions/inversions within a 10 kb region surrounding the target sites at all three loci, similar to the nucleases, the chromosomal on-target aberrations were qualitatively different and included a high proportion of insertions. Taken together, our data indicate that double-nickase approaches combine efficient editing with greatly reduced off-target effects but still leave substantial chromosomal aberrations at on-target sites., Competing Interests: Declaration of interests T.C. is an advisor to Cimeio Therapeutics, Excision BioTherapeutics, GenCC, and Novo Nordisk. T.C. and T.I.C. have sponsored research collaborations with Cellectis and Cimeio Therapeutics, respectively. T.C., M.B., and G.A. hold a patent on CAST-seq (US11319580B2)., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Prediction of health risks associated with exposure to mixed beams of high- and low-linear energy transfer ionizing radiation is based on the assumption that the biological effect caused by mixed radiation equals the sum of effects resulting from the action of individual beam components. Experimental studies have demonstrated that the cellular effects in cells exposed to mixed radiations are higher than that calculated based on the assumption of additivity. The present work contains a comparative analysis of published results on chromosomal aberrations in human peripheral blood lymphocytes exposed to mixed beams of alpha particles and X-rays with computer simulations using the PARTRAC program based on Monte Carlo methods. PARTRAC was used to calculate the levels of DNA single-strand breaks (SSB) and double-strand breaks (DSB—both complex and simple) and the level of chromosomal aberrations. SSB and DSB yields were found to be additive. A synergistic effect was obtained at the level of chromosomal aberrations, being in good agreement with the experimental results. This result demonstrates that the synergistic action of mixed beams results from processing of SSB and DSB and not from their initial frequencies. The level of synergy was dependent on the composition of the mixed beam, with highest level at 50:50 ratio of alpha particles and X-rays.

Background: A number of factors are known to reduce fertility rate in animals and one of the important categories of such factors is chromosome anomalies. They can occur with or without causing phenotypic abnormalities on animals; in some cases, they may directly affect meiosis, gametogenesis and the viability of conceptus. In many instances, balanced structural rearrangements can be transmitted to offspring, affecting fertility in subsequent generations. Aim: This work investigated the occurrence of chromosome aberrations in Rusa timorensis, Rusa unicolor and Axis axis raised in a nucleus deer farm in Malaysia with a history of declining fertility of unknown origin. Materials & methods: Blood samples were collected from 60 animals through venipuncture, cultured for 72 h and arrested at metaphase. SmartType® and Ideokar® software were used to karyotype the chromosomes. Results: We found 15 out of the 60 animals screened from both sexes harbor some form of chromosome aberration. Chromosomal aberrations exist at the rate of 25% and may not be unconnected with the observed reduced fertility on the farm. Further investigations should be carried out, especially on the offspring of the studied animals to transmission of these aberrations. The animals that are confirmed to transmit the chromosomal aberrations should be culled to arrest the propagation of their abnormalities.

There is a concern about stablishing the clinical risk of drugs used for cancer treatment. In this study, the cytotoxic, clastogenic and genotoxic properties of cis-tetraammine(oxalato)ruthenium(III) dithionite - cis-[Ru(C2O4)(NH3)4]2(S2O6), were evaluated in vitro in human lymphocytes. The mitotic index (MI), chromosomal aberrations (CA) and DNA damage by comet assay were also analyzed. The MTT test revealed that the ruthenium compound showed a slight cytotoxic effect at the highest concentration tested. The IC50 value for the compound after 24 hours of exposure was 185.4 µM. The MI values of human peripheral blood lymphocytes treated with 0.015, 0.15, 1.5 and 150 µM of cis-[Ru(C2O4)(NH3)4]2(S2O6) were 6.1, 3.9, 3.2 and 0.2%, respectively. The lowest concentration, 0.015 µM, did not show any cytotoxic activity. The CA values for the 0.015, 0.15 and 1.5 µM concentrations presented low frequency (1.5, 1.6 and 2.3%, respectively), and did not express clastogenic activity when compared to the negative control, although it was observed clastogenic activity in the highest concentration tested (150 µM). The results obtained by the comet assay suggest that this compound does not present genotoxic activity at lower concentrations. The results show that cis-[Ru(C2O4)(NH3)4]2(S2O6) has no cytotoxic, clastogenic or genotoxic in vitro effects at concentrations less than or equal to 0.015 µM. This information proves as promising in the treatment of cancer and is crucial for future trials.

The cytogenetic study on the meristematic tissues of basil (Ocimum basilicum L.) aimed to evaluate some cytotoxic effects induced by two heavy metals (cadmium - Cd and zinc - Zn) applied in three different concentrations: 10, 50 and 100 ppm. Cytogenetic tests reveal a decrease of the mitotic index and the occurrence of various chromosomal aberrations following heavy metal treatments. The cell division was significantly affected, especially in the case of Cd treatment, which showed the highest degree of toxicity in all variants compared to control variant. Instead, Zn has a lower degree of toxicity but only at concentrations of 50 ppm and 100 ppm. Types of chromosomal aberrations were relatively varied, being randomly distributed and concentration dependent, for both Cd and Zn. Were observed cells with large nucleus and disorganized-looking; interphases with pyknotic nucleus; cells with laggard chromosomes, pyknotic and sticky chromosomes, as well as cells with telophase bridge. The results reveal that Cd (at all tested concentrations) and Zn in concentrations higher than 10 ppm exhibit significant cytotoxic potential to Ocimum basilicum L. as a result of the effects reported in cell divisions of the meristematic tissues. We can also appreciate that the Ocimum basilicum L. species could be used as a test plant to determine the degree of soil pollution with heavy metals.

Results of the research on the phytotoxic, cytotoxic and genotoxic effects revealed in common wheat (Triticum aestivum L.) plants germinated from seeds treated with nanooxide iron (Fe2O3 NP) and crystalline iron oxide (Fe2O3 cr.) are described. Stimulating effects of the majority of their studied concentrations on cell division and tissue growth were demonstrated. Effects of Fe2O3 NP and Fe2O3 cr. also have been studied on growth and development of the tomato (Lycopersicon esculentum L.) tissues cultivated in vitro. It has been shown that Fe2O3 NP and Fe2O3 cr. induced both inhibitory and stimulating effects depending on the concentrations applied.

Soil forms a huge reservoir of nutrients that sustains life on earth. Anthropogenic and natural impacts have led to degradation of land which declines the overall quality of soil, water or vegetation. The present study involves comparison of genotoxicity of soil procured from two different agricultural sites, pesticide treated soil (PTS) and vermicompost treated soil (VTS). The soil was physico-chemically characterized and showed significant differences in terms of cytotoxicity (root length; mitotic index) and genotoxicity (chromosomal aberrations) in Allium cepa test. The mitotic index of the control after 24 and 48 h was found to be 26.1 ± 1.6 and 26.1 ± 1.3 respectively. Mitotic index was reduced to 10.3 ± 0.9 and 9.7 ± 0.6 in 100% PTS and 24.4 ± 1.7 and 25.4 ± 0.8 in 100% VTS after 24 and 48 h of exposure, respectively. Clastogenic aberrations were found to be highest (54.5%) in 100% PTS which was significantly different from VTS extract. The PTS extracts incurred significantly more cytotoxic and genotoxic effects on A. cepa in comparison to VTS. The result indicates that addition of vermicompost in agriculture field acts as soil ameliorator and plays an important role in promotion of cell division and proliferation, hence good for the plant health and crop productivity.

Abstract Background Genotoxicity is an important toxicological endpoint due to the link to diseases such as cancer. Therefore, an increased understanding regarding genotoxicity and underlying mechanisms is needed for assessing the risk with exposure to nanoparticles (NPs). The aim of this study was to perform an in-depth investigation regarding the genotoxicity of well-characterized Ni and NiO NPs in human bronchial epithelial BEAS-2B cells and to discern possible mechanisms. Comparisons were made with NiCl2 in order to elucidate effects of ionic Ni. Methods BEAS-2B cells were exposed to Ni and NiO NPs, as well as NiCl2, and uptake and cellular dose were investigated by transmission electron microscopy (TEM) and inductively coupled plasma mass spectrometry (ICP-MS). The NPs were characterized in terms of surface composition (X-ray photoelectron spectroscopy), agglomeration (photon cross correlation spectroscopy) and nickel release in cell medium (ICP-MS). Cell death (necrosis/apoptosis) was investigated by Annexin V-FITC/PI staining and genotoxicity by cytokinesis-block micronucleus (cytome) assay (OECD 487), chromosomal aberration (OECD 473) and comet assay. The involvement of intracellular reactive oxygen species (ROS) and calcium was explored using the fluorescent probes, DCFH-DA and Fluo-4. Results NPs were efficiently taken up by the BEAS-2B cells. In contrast, no or minor uptake was observed for ionic Ni from NiCl2. Despite differences in uptake, all exposures (NiO, Ni NPs and NiCl2) caused chromosomal damage. Furthermore, NiO NPs were most potent in causing DNA strand breaks and generating intracellular ROS. An increase in intracellular calcium was observed and modulation of intracellular calcium by using inhibitors and chelators clearly prevented the chromosomal damage. Chelation of iron also protected against induced damage, particularly for NiO and NiCl2. Conclusions This study has revealed chromosomal damage by Ni and NiO NPs as well as Ni ionic species and provides novel evidence for a calcium-dependent mechanism of cyto- and genotoxicity.

Summary: Approximately 15–25% of pregnancies end in spontaneous abortion, which is an expulsion from the mother body of the fetus weighing less than 500 g or before the 20th week of gestation. Determining abortions etiology is difficult due to its multifactorial character. Chromosomal abnormalities cause 38.6–80% of miscarriages. The largest group (93%) of chromosomal aberrations found in miscarried fetuses are numerical changes – aneuploidies and polyploidies. Much rarer (7%) are unbalanced structural aberrations, which can arise de novo or can be inherited from a carrier parent. In couples with spontaneous abortions, reciprocal chromosomal translocations (RCT) occur the most frequently, next are Robertsonian translocations and inversions. More complex chromosome abnormalities, e.g. double aneuploidies are found in 3.8% of fetuses. Another group of causes responsible for abortions are monogenic diseases of embryo or fetus resulting from autosomal dominant, autosomal recessive or X-linked mutations. Among mutations which may contribute to pregnancy loss are factor V Leiden gene mutations (c.1601G>A, earlier 1691G>A) and prothrombin gene mutation (c.97G>A, earlier 20210G>A). The research on mutations in candidate genes, eg.: ALOX15, CR1, CYP1A1, CYP17, CYP2D6, FOXP3, HLA-G, IL-6, KHDC3L, NLRP7, NOS3, PLK4, SYCP3, TLR3, TNF, TP53 and VEGFA is still ongoing. [ABSTRACT FROM AUTHOR]

The wide use of metal nanoparticles has raised the concern of their release in the environment and their biological safety. The use of silver nanoparticles (Ag NPs) as effective antimicrobial agent is also questioned due to the resistance developed by pathogens and the biosafety for the host. The genotoxicity caused by such particles need to be assessed to ensure that they are safe to use. In this study, green synthesized Ag NPs were used and the biosafety in terms of genotoxicity was evaluated by in vitro Chromosome aberration (CA) assay using short-term cultures of human peripheral blood. The physicochemical parameters of these Ag NPs were studied for stability in nano form. The transmission electron microscopy (TEM) and energy-dispersive spectroscopy (EDS) were carried out. The dynamic light scattering and zeta potential measurements revealed stable nano particles. The UV visible & fluorescence spectroscopy for binding affinity of Ag NPs did not suggest significant DNA interaction. The exposure of whole blood cultures to Ag NPs for 24 h showed dose dependent increase in frequency of CA per cell at 350, 650 and 1000 µL (P = NS, P < 0.05 and P < 0.001 respectively). Our study demonstrates that genotoxicity of Ag NPs can be reduced by the use of green synthesized Ag NPs at low dose exposure, which will guide selecting right concentrations of NP for further in vivo studies, and future applications. [ABSTRACT FROM AUTHOR]

Manganese and Nickel doped Zinc Ferrite (MNZF) nanoparticle Mn0.3Ni0.3Zn0.4Fe2O4 is used in fabrication of room temperature (25-30°C) NH3 gas sensor in large scale industries. However, there are no studies available on its toxic effects. Hence, in the present study, we assessed the genotoxic effect of various doses (125, 250 and 500 mg/kg) of the MNZF nanoparticle (NP) in Swiss albino mice Mus musculus employing the chromosomal aberration test, micronucleus test and single cell gel electrophoresis assay (comet assay). The NP was orally gavaged for 15 consecutive days. Dose-dependent study was conducted at 24 h after the last dose of gavage and time-dependent response was studied for 250 mg/kg at 24, 48 and 72 h of treatment. All the parameters employed showed a statistically significant dose-dependent increase of genetic damage indicating the genotoxic effect of this NP in Swiss albino mice. Proper precautions should be undertaken on handling this NP to avoid contact with it either through respiration or ingestion. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that telomere shortening and/or loss are risk factors for infertility.Design: Retrospective analysis of the telomere status in patients with infertility using conventional cytogenetic data collected prospectively.Setting: Academic centers.Patient(s): Cytogenetic slides with cultured peripheral lymphocytes from 50 patients undergoing fertility treatment and 150 healthy donors, including 100 donors matched for age.Intervention(s): Cytogenetic slides were used to detect chromosomal and telomere aberrations.Main Outcome Measure(s): Telomere length and telomere aberrations were analyzed after telomere and centromere staining.Result(s): The mean telomere length of patients consulting for infertility was significantly less than that of healthy donors of similar age. Moreover, patients with infertility showed significantly more extreme telomere loss and telomere doublet formation than healthy controls. Telomere shortening and/or telomere aberrations were more pronounced in patients with structural chromosomal aberrations. Dicentric chromosomes were identified in 6/13 patients, with constitutional chromosomal aberrations leading to chromosomal instability that correlated with chromosomal end-to-end fusions.Conclusion(s): Our findings demonstrate the feasibility of analyzing telomere aberrations in addition to chromosomal aberrations, using cytogenetic slides. Telomere attrition and/or dysfunction represent the main common cytogenetic characteristic of patients with infertility, leading to potential implications for fertility assessment. Pending further studies, these techniques that correlate the outcome of assisted reproduction and telomere integrity status may represent a novel and useful diagnostic and/or prognostic tool for medical care in this field. [ABSTRACT FROM AUTHOR]

The linear-quadratic (LQ) model represents a simple and robust approximation for many mechanistically-motivated models of radiation effects. We believe its tendency to overestimate cell killing at high doses derives from the usual assumption that radiogenic lesions are distributed according to Poisson statistics. In that context, we investigated the effects of overdispersed lesion distributions, such as might occur from considerations of microdosimetric energy deposition patterns, differences in DNA damage complexities and repair pathways, and/or heterogeneity of cell responses to radiation. Such overdispersion has the potential to reduce dose response curvature at high doses, while still retaining LQ dose dependence in terms of the number of mean lethal lesions per cell. Here we analyze several irradiated mammalian cell and yeast survival data sets, using the LQ model with Poisson errors, two LQ model variants with customized negative binomial (NB) error distributions, the Padé-linear-quadratic, and Two-component models. We compared the performances of all models on each data set by information-theoretic analysis, and assessed the ability of each to predict survival at high doses, based on fits to low/intermediate doses. Changing the error distribution, while keeping the LQ dose dependence for the mean, enables the NB LQ model variants to outperform the standard LQ model, often providing better fits to experimental data than alternative models. The NB error distribution approach maintains the core mechanistic assumptions of the LQ formalism, while providing superior estimates of cell survival following high doses used in radiotherapy. Importantly, it could also be useful in improving the predictions of low dose/dose rate effects that are of major concern to the field of radiation protection. [ABSTRACT FROM AUTHOR]

The study utilized molecular-genetic, cytogenetic, and statistical analyzes methods. A cytogenetic and molecular genetic analysis of the inhabitants of the villages of Amangeldy, Belbulak, in whose territory warehouses of unused pesticides are located, was carried out. Residents of the Basshi village, on the territory of which there are no products of disposal of pesticides, were taken as control. Cytogenetic analysis showed a high level of chromosomal aberrations for the inhabitants of the Belbulak village, an increased level for the inhabitants of the Amangeldy village and a low level in the Basshi cohort. Molecular genetic analysis did not reveal a significant correlation between the polymorphisms of the XRCC1 Arg194Trp, XRCC3 Thr241Met and XPD Lys751Gln genes and the frequency of chromosomal aberrations. However, study determined the associative relationship of the polymorphism of the DNA repair gene XRCC1 Arg399Gln with the development of cardiovascular diseases in a population living near foci of pesticidal contamination. [ABSTRACT FROM AUTHOR]

Background: Green synthesis of metal and metal oxide nanoparticles (NPs) using plant extract performs a significant role as it is a promising alternative to the conventional chemical method in nanotechnology. Aims: In this paper, we report an environmentally benign method for the synthesis of silver nanoparticles (AgNPs) and zinc oxide nanoparticles (ZnONPs) using leaf extract of Garcinia livingstonei, and their mitotic activities were investigated using the root tip of Cicer arietinum. Objectives: The as-prepared NPs were characterized by ultraviolet-visible spectroscopy, infrared spectroscopy (FT-IR), X-ray diffraction (XRD), atomic force microscopy (AFM), and high-resolution transmission electron microscopy (HR-TEM). Analysis of FT-IR spectrum revealed that certain functional groups behaved as reducing and stabilizing agents in the formation of nanostructures. The crystalline nature of the AgNPs and ZnONPs was confirmed by XRD analysis. The size and shape of the as-obtained materials were found using HR-TEM analysis and were in the range of 5-65 nm and 38-94 nm for AgNPs and ZnONPs, respectively. Further, the root cells of C. arietinum were treated with both AgNPs and ZnONPs in different concentrations (5, 25, 50, and 100 µg/ml) for 24 h at the interval of 3, 6, 12, and 24 h along with distilled water as control. Results: The study clearly indicated that the AgNPs and ZnONPs showed an inhibitory effect on the cell division in root tip cells and caused a decrease in their mitotic index (MI) values. The reduction in MI in AgNPs is more evident than that of ZnONPs when compared to control. Aberrations in chromosomal behavior such as micronucleus, sticky chromosomes, bridges, multipolar anaphase, laggard, and c-metaphase were also observed. Conclusion: From the results, it is evident that the percentage of MI is inversely proportional, and chromosomal aberrations (CAs) are directly proportional to the concentration and duration of exposure. [ABSTRACT FROM AUTHOR]