Mutagenesis最新文献

{"title":"Changes in telomere length and mitochondrial DNA copy number in the colorectal adenoma-carcinoma sequence.","authors":"Anna Valickova, Kristyna Tomasova, Katerina Balounova, Josef Horak, Michal Kroupa, Petr Hanak, Natalie Danesova, Jiri Jungwirth, Jan Kral, Tomas Hucl, Pavel Kohout, Sandra Summerova, Michaela Schneiderova, Ludmila Vodickova, Pavel Vodicka, Veronika Vymetalkova, Sona Vodenkova","doi":"10.1093/mutage/geag009","DOIUrl":"10.1093/mutage/geag009","url":null,"abstract":"<p><p>Colorectal adenomas are anomalous growths of the intestinal epithelium and are considered precursors to colorectal cancer (CRC). Identifying early-stage CRC biomarkers is essential for reducing its high mortality rate. This study hypothesizes that the association of telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN) could serve as a biomarker for the adenoma or CRC formation. TL, mtDNA-CN, telomerase reverse transcriptase (TERT), and mitochondrial transcription factor A (TFAM) expressions were studied in 132 adenoma and 95 early-stage CRC patients. TL and mtDNA-CN were measured by multiplex quantitative polymerase chain reaction (qPCR). Expression of TERT and TFAM was measured by reverse transcription-qPCR. Significant TL shortening was observed in adenomas (P = 8.96e-14), tumor-node-metastasis (TNM) I (P = 3.49e-05), and TNM II (P = 2.29e-04) stages compared to the adjacent mucosa. This tendency was also contingent on TERT expression. Differential TFAM expression was observed in all groups, but an elevated relative mtDNA-CN was, compared to the adjacent mucosa, detected only in adenomas (P = 1.50e-08), where it correlated with TL (P = 4.10e-03). Notably, mtDNA-CN levels were significantly higher in adenomas than in early-stage tumors (TNM I, P = 2.00e-02; TNM II, P = 2.40e-02), suggesting a progressive decline during tumorigenesis. We have provided fresh insights into the crosstalk between telomere and mitochondrial biology in CRC precursors. These findings hold promise in understanding adenoma formation and CRC progression, as mtDNA-CN elevation and its association with TL were specific to precancerous lesions and were lost with progression to tumor.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":"142-155"},"PeriodicalIF":3.1,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovating the buccal micronucleus cytome assay to improve its utility as a biomarker of in vivo genotoxicity.","authors":"Michael Fenech, Claudia Bolognesi, Armen Nersesyan, Siegfried Knasmueller, Stefano Bonassi","doi":"10.1093/mutage/geaf023","DOIUrl":"10.1093/mutage/geaf023","url":null,"abstract":"<p><p>The Buccal Micronucleus Cytome (B-MNcyt) assay is used worldwide to study chromosomal abnormalities and environmental genotoxicity and cytotoxicity in humans. The aim of this article is to discuss the strengths and limitations of the B-MNcyt assay and to identify emerging opportunities to further improve and validate its use. This can be achieved by innovating and evolving the B-MNcyt assay by identifying and solving important knowledge and technological gaps that hinder its utility. The cells examined in the B-MNcyt assay are squamous epithelial cells that can be easily collected from the inside of the mouth. These cells are postmitotic cells generated from the proliferative basal layer and may contain micronuclei (MN). MN can be generated during mitosis of the basal cells prior to their differentiation into squamous cells. The B-MNcyt assay is increasingly being used to measure DNA damage induced in vivo by environmental genotoxins. Results with this assay have been shown to correlate positively with MN frequency measured using the well-validated lymphocyte cytokinesis-block micronucleus cytome (L-CBMNcyt) assay. However, the B-MNcyt assay has some important limitations that need to be addressed to achieve a similar level of validation and applicability to that of the L-CBMNcyt assay. These include the lack of (i) evidence that the buccal MN frequency predicts disease risk in prospective studies; (ii) an automated scoring system to score MN in buccal cells, which is essential to achieve statistically robust results and to improve the feasibility of the assay in population studies; (iii) sufficient research on the kinetics of MN expression in buccal cells to define optimal time frames to score MN after acute exposure or during chronic genotoxin exposure; and (iv) studies to test the suitability of using the B-MNcyt assay for radiation exposure biodosimetry. This article discusses these issues and provides some suggestions on how to address them.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":"28-36"},"PeriodicalIF":4.3,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of cigarette smoking on genetic stability, cell division, and cytotoxicity in buccal cells of old and young women.","authors":"Armen Nersesyan, Michael Kundi, Rafayel Muradyan, Georg Wultsch, Miroslav Mišík, Franziska Ferk, Siegfried Knasmueller","doi":"10.1093/mutage/geaf003","DOIUrl":"10.1093/mutage/geaf003","url":null,"abstract":"<p><p>We investigated the impact of cigarette smoking, daily exposure to tar and nicotine, and the duration of smoking on genetic instability (chromosomal damage-micronuclei, MN, nuclear buds-gene amplification) as well as on disturbances in mitosis (resulting in binucleated cells). Furthermore, we analyzed markers of cytotoxic effects (such as the formation of condensed chromatin, pyknotic, karyolytic, and karyorrhectic cells) and the mitotic activity of the oral mucosa. These parameters were monitored in groups of old (postmenopausal) and young (premenopausal) smoking and nonsmoking women (n = 25/group). We found no differences in the MN frequencies in the non-smoking groups and only a moderate (not significant) increase of MN in both groups of smokers. However, we observed a clear increase in markers of genomic instability in both smoking groups. Furthermore, the mitotic activity of cells in the mucosa and of anomalies caused by acute cytotoxicity was higher in both smoking groups. Nicotine uptake was associated with pronounced acute toxic effects and increased cell division rate. Chromosomal damage (MN) was higher in individuals who consumed high amounts of tar (this effect was not significant) and caused moderate acute toxicity. Our findings indicate (i) that age and hormonal status have no strong impact on the genotoxic and cytotoxic effects in smoking women, (ii) consumption of up to 30 cigarettes/day does not cause chromosomal damage in buccal cells, however, positive results were found in earlier studies in heavy smokers, (iii) smoking increased markers which reflect genetic instability and the division rate of oral mucosa cells. These effects may play a role in the neoplastic transformation of cells in the upper respiratory tract in smokers. The duration of smoking was associated with a slight (not significant) increase in the mitotic activity and of chromosomal damage and with moderate acute cytotoxicity.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":"73-80"},"PeriodicalIF":3.1,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13019528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The micronucleus assay in exfoliated buccal cells for occupational exposure studies: an overview.","authors":"Georg Wultsch, Armen Nersesyan, Miroslav Mišík, Franziska Ferk, Karin Schelch, Maximilian Scharnagl, Michael Grusch, Siegfried Knasmüller","doi":"10.1093/mutage/geaf018","DOIUrl":"10.1093/mutage/geaf018","url":null,"abstract":"<p><p>This review describes the use of the micronucleus (MN) assay with exfoliated cells from the oral mucosa in occupational studies. The molecular mechanisms leading to formation of MN (chromosomal breakage and aneuploidy) are well known. In total, 222 articles have been published since the method was developed in 1982. The majority of investigations were conducted with agricultural workers, followed by petrol station attendants, painters, pathology/anatomy lab workers, and miners. Positive results were reported in the majority of studies (86%); Brazil, Italy, Mexico, and Turkey being the most productive countries. The use of this technique increased substantially in recent years, and a recent correlation analysis with data from MN studies with lymphocytes indicates that the method is useful for predicting the cancer risks of chemically and radiation-exposed workers. The methodological quality of the studies increased in recent years since standardized and validated guidelines have been published. However, major shortcomings are still the lack of adequate matching (in particular in regard to nutrition and intake of dietary supplements), the lack of chemical exposure measurements, and the use of inadequate (DNA-nonspecific) stains. The most pronounced effects were seen in metal production workers, miners, petrol station attendants, agricultural workers, and pathologists. The sampling of cells from the oral cavity is noninvasive and requires no cultivation under sterile conditions is required. The currently available data indicate that this fast and easy-to-perform procedure provides valuable information about combined effects of chemical exposures and about the efficiency of safety measurements. Therefore, it should be used in the future for the routine surveillance of workers.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":"4-15"},"PeriodicalIF":3.1,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13019526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep learning and object detection methods for scoring cell types within the human buccal cell micronucleus and cytome assays for human biomonitoring.","authors":"Eloise Smith, Jade Wagman, Claire Barnes, Paul Rees, George Johnson","doi":"10.1093/mutage/geaf026","DOIUrl":"10.1093/mutage/geaf026","url":null,"abstract":"<p><p>Micronuclei (MN) are critical biomarkers for pathological conditions, yet their manual scoring is inherently laborious and prone to significant interobserver variability, limiting the reliability and scalability of genotoxicity assessments. Recent advancements in deep learning and computer vision have revolutionized automated MN detection in various assay samples, enhancing accuracy and efficiency and reducing human bias. While these artificial intelligence (AI)-powered techniques have been demonstrated in in vitro genotoxicity testing, their application to the minimally invasive buccal micronucleus cytome (BMCyt) assay for human biomonitoring remains largely unexplored. The BMCyt assay, invaluable for assessing genotoxic damage in environmentally exposed populations, presents unique challenges, including sample variability, confounding factors, and the complexity of scoring multiple cytogenetic endpoints. This review covers the evolution of AI-based MN detection, analysing key methodologies and advancements. It highlights the untapped potential of integrating AI into the BMCyt assay to overcome current analytical limitations, improve reproducibility, increase throughput, and eliminate observer bias. By facilitating more robust and scalable genomic damage monitoring, AI integration will significantly enhance the utility of the BMCyt assay in large-scale epidemiological studies and human biomonitoring.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":"37-45"},"PeriodicalIF":3.1,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13019529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145513505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Buccal Micronucleus (BMN) Cytome assay: enhancing its applications by addressing challenges and exploring new opportunities.","authors":"Emanuela V Volpi, Michael Fenech","doi":"10.1093/mutage/geag006","DOIUrl":"10.1093/mutage/geag006","url":null,"abstract":"","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":"1-3"},"PeriodicalIF":4.3,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aneuploidy in exfoliated buccal cells: mechanisms, methods, and future perspectives.","authors":"Micheline Kirsch-Volders, Miroslav Mišík, Michael Fenech","doi":"10.1093/mutage/geaf024","DOIUrl":"10.1093/mutage/geaf024","url":null,"abstract":"<p><p>Aneuploidy and polyploidy have a major impact in congenital and acquired diseases, in particular in cancer development. This mini-review highlights the use of exfoliated buccal cells as a non-invasive tool for monitoring aneuploidy. It offers a mechanistic overview and illustrative diagrams addressing five key areas: (i) the causes of aneuploidy; (ii) cell kinetics and aneuploidy induction in epithelial buccal cells; (iii) the methods for the detection of aneuploidy; (iv) the scientific and medical domains applying aneuploidy detection in exfoliated buccal cells; (v) the knowledge gaps and future research perspectives. Although well validated protocols, automated systems and specific probes allowing discrimination between chromosome aberration, aneuploidy and polyploidy in exfoliated buccal cells are available, large-scale cohort human studies remain lacking. These studies are crucial for evaluating aneuploidy in populations exposed to genotoxic agents or at risk for buccal dysplasia. Future validation and predictivity studies should compare fluorescence in situ hybridization and total DNA content methods such as densitometry or flow cytometry, in exposed individuals and control groups with careful control of confounding factors and adherence to standardized reporting guidelines. In addition, assessment of aneuploidy frequencies in parallel in lymphocytes and exfoliated buccal cells in the same populations would allow to compare their predictive value in both tissues. Moreover, mechanistic studies are also needed to better understand the sources of variability in aneuploidy and how buccal cell biology compares to other cell types. In conclusion, due to their ease of collection and non-invasive nature, exfoliated buccal cells represent a promising tool for aneuploidy testing for risk assessment of environmental or occupational exposures and disease prediction and monitoring.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":"16-27"},"PeriodicalIF":3.1,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13019530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145302033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The micronucleus assay in exfoliated buccal cells induced by lifestyle factors: an overview.","authors":"Siegfried Knasmüller, Armen Nersesyan, Miroslav Mišík, Franziska Ferk, Michael Grusch, Ivana Z Matić, Michael Kundi, Georg Wultsch","doi":"10.1093/mutage/geag008","DOIUrl":"10.1093/mutage/geag008","url":null,"abstract":"<p><p>We describe the impact of lifestyle related factors on the formation of micronuclei (MN) in buccal cells. It is known that consumption of alcohol and of other drugs including tobacco and other plants cause damage of the genetic material and leads to adverse health effects. Overall, 235 articles were evaluated in total. Tobacco smoking, i.e., consumption of cigarettes (75 publications), water pipes (11 publications) and crack smoking (5 publications) caused mainly positive effects, while negative results were obtained with pure marijuana (2 publications). Chewing habits (smokeless tobacco (27 publications) and betel with and without tobacco (23 publications) caused induction of MN in cells from the oral cavity (numbers indicate the number of publications). A study concerning khat chewing yielded a positive finding while reduction of MN was seen in consumers of coca leaves. Investigations concerning the effects of alcohol (11 publications), meat consumption (3 publications) and studies concerning the impact of the body mass index and body fat (4 publications) led to inconsistent results. No evidence of MN induction was observed in studies on continuous physical exercise (2 publications). Furthermore, exhaustive sporting activities also showed no indications of chromosomal damage (2 publications). A number of studies (in total 22 publications) were realized to investigate the effects of mobile phone specific radiation. The exposure was not adequately assessed in these investigations with questionnaires, furthermore, frequently inadequate stains (11 publications). The findings are controversial, and a clear negative result was obtained in a recent controlled intervention study. Overall the results indicate that the MN assay with buccal cells can be used to monitor chromosomal damage caused by smoking and chewing habits and to predict adverse health effects in the respiratory system and on the upper gastrointestinal tract. To draw firm conclusions about the effects of nutrition, mobile phone use, physical exercise, and body weight, further well-controlled trials are needed.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":"46-72"},"PeriodicalIF":3.1,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146213817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High correlation between micronuclei in lymphocytes and buccal cells in humans provides further validation of their use as biomarkers of DNA damage and cancer risks in vivo.","authors":"Armen Nersesyan, Stefania Proietti, Siegfried Knasmueller, Stefano Bonassi, Michael Fenech","doi":"10.1093/mutage/geaf006","DOIUrl":"10.1093/mutage/geaf006","url":null,"abstract":"<p><p>Micronuclei (MN) are cellular structures containing chromosome fragments or whole chromosomes that fail to be incorporated into the main nuclei during mitosis. MN measured in lymphocytes using the cytokinesis-block method and MN in buccal cells are among the most widely used methods for measuring DNA damage in humans. However, it remains unclear whether they correlate well with each other. This has important implications regarding whether existing evidence linking MN in lymphocytes to prospective cancer risk can also be extended to MN in buccal cells, a much less invasive approach. We therefore systematically reviewed results from published studies that reported MN frequencies simultaneously in buccal cells and lymphocytes. Data were extracted from a set of 81 study groups reported in 62 publications. The overall frequency of MN in groups exposed to increased risk of DNA damage was 2.54 times higher compared to controls (95% CI: 2.06-3.01) in buccal cells and 2.43 times higher (95% CI: 1.92-2.93) in lymphocytes. Frequencies of MN in populations investigated for occupational or environmental exposure to genotoxins, various diseases, and poor nutrition/lifestyle were also compared in each study and for each tissue (lymphocytes and buccal mucosa) with frequencies in control subjects using the mean ratio (MR). Concordance between the two MN assays was evaluated by comparing MRs for primary exposure in all studies using a correlation analysis. The overall Pearson correlation index was 0.768 (0.877 for case-control studies and 0.998 for intervention studies), showing that MR estimates from the two assays were highly and significantly correlated (P < .001). The results from this investigation indicate that data obtained using the buccal MN assay reflect results obtained using the lymphocyte cytokinesis-block MN assay. This suggests that the buccal MN assay may also identify those at increased risk of tumorigenesis. Prospective studies will ultimately be required to completely verify this hypothesis.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":"81-89"},"PeriodicalIF":4.3,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Evolution and Application of Animal-Free Models in Drug Discovery and Disease Mechanism Research.","authors":"Eve Jarman, Cristina Tufarelli, Karen Brown","doi":"10.1093/mutage/geag003","DOIUrl":"https://doi.org/10.1093/mutage/geag003","url":null,"abstract":"<p><p>Animal models have been key for disease mechanism research for years, but ethical concerns partly fuelled by the realisation that not all diseases can be recapitulated in animal systems have led to regulatory changes that are driving a shift towards animal-free alternatives. As regulations continue to evolve, the transition to animal-free models is becoming increasingly crucial for laboratories aiming to comply with new standards without compromising on scientific progress. The past decade has seen a boost in the development of animal-free three-dimensional models including explants, co-cultures, spheroids, organoids, and organ-on-chip systems, creating a varied landscape that has significantly transformed disease research. These models incorporate advancements in stem cell technology, bioengineering, and microfluidics to provide more physiologically relevant systems that bridge the gap between traditional two-dimensional cell culture and in-vivo studies. Whilst traditional two-dimensional cultures offer a cost-effective method with replicable results, they fail to accurately represent the natural structure of tissues and cell-cell interactions. By contrast, animal-free culture systems provide a more appropriate representation of human physiology and tissue architecture with relevance to in-vivo conditions. Therefore, these models enable more translatable research outcomes and have the potential to provide data for the reduction of the high failure rates currently marring clinical trials. This review explores the evolution, advantages, and applications of animal-free models in advancing human disease research and refining preclinical studies with an emphasis on cancer research.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}