Mutagenesis最新文献

{"title":"DNA damage in oral mucosal epithelial cells cultured in complex and xenobiotic-free media: a comparison study.","authors":"Joao Victor Cabral, Sona Vodenkova, Kristyna Tomasova, Ludmila Vodickova, Naouale El Yamani, Elise Rundén Pran, Maria Dusinska, Adam Safanda, Katerina Jirsova","doi":"10.1093/mutage/geaf008","DOIUrl":"10.1093/mutage/geaf008","url":null,"abstract":"<p><p>In this study, we evaluated the genomic stability of oral mucosal epithelial cells (OMECs) cultured in complex media (COM) and xenobiotic-free media (XF) to assess their potential clinical application for limbal stem cell deficiency (LSCD) treatments. OMECs serve as a promising autologous cell source for bilateral LSCD treatment, offering an alternative to limbal epithelial cells (LECs). However, genomic integrity is crucial to ensure the long-term success of transplanted cells. We performed micronucleus (MNi) tests and comet assays to compare DNA damage in OMECs cultured in both media types. The results indicated no significant differences in cell morphology, viability, or size between the two conditions. The MNi frequency was similar, with 5.67 and 6.17 MNi per 1,000 cells in COM and XF conditions, respectively. Comet assay results showed low levels of strand breaks (SBs) and oxidized DNA lesions in both media, with XF showing a slightly lower, albeit statistically insignificant, percentage of tail DNA for net Fpg-sensitive sites. Our findings suggest that OMECs can be effectively cultivated in either COM or XF media without inducing significant DNA damage, supporting the potential use of XF media in clinical settings to reduce contamination risks. This study underscores the importance of genomic stability in cultured cells for ocular surface transplantation, contributing valuable insights into optimizing culture conditions for safer and more effective clinical applications.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":"526-532"},"PeriodicalIF":4.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528989","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":"Terminalia ivorensis demonstrates antioxidant properties and alters proliferation, genomic instability, and migration of human colon cancer cells in vitro.","authors":"Aliu Moomin, Rachel M Knott, Wendy R Russell, Mary P Moyer, Susan J Duthie","doi":"10.1093/mutage/geae026","DOIUrl":"10.1093/mutage/geae026","url":null,"abstract":"<p><p>Colorectal cancer is a global killer that causes approximately 940 thousand deaths annually. Terminalia ivorensis (TI) is a tropical tree, the bark of which is used in African traditional medicine for the treatment of diabetes, malaria, and ulcer. This study investigated TI as a potential anticancer agent in human colon cells in vitro. TI was extracted sequentially with petroleum ether, chloroform, ethyl acetate, and ethanol. Antioxidant activity was assessed by DPPH and FRAP, and differential effects on cell viability, growth, DNA damage, DNA repair, and migration were measured in human colon cancer cells (CaCo-2) and/or non-cancerous human colonocytes (NCM460). The TI phytochemicals most strongly associated with these effects were identified by partial least-squares discriminant analysis. DPPH and FRAP activity was highest in TI ethyl acetate and ethanol extracts (P = .001). All TI extracts significantly inhibited cell viability and growth and induced DNA damage and inhibited DNA repair in both cell models. The majority of TI extracts were significantly (P = .01) more toxic to cancer cells than non-cancerous colonocytes. DNA repair was significantly (P = .001) inhibited in CaCo-2 cells by ethyl acetate extract compared with NCM460 cells. Migration was also significantly inhibited (P < .001) in CaCo-2 by ethyl acetate (80%) and ethanol extracts (75%). Specific benzoic acids, flavonoids, and phenols were identified to be strongly associated with these effects. TI displayed strong antioxidant activity and specific anticancer effects by inducing cell death and DNA damage, and by inhibiting DNA repair, cell proliferation, and migration.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":"498-511"},"PeriodicalIF":4.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504439","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":"DNA damage, apoptosis, and serum inflammatory marker levels, but not white blood cell counts, are related to occupational exposure to waste anesthetic gases during medical residency: a longitudinal study.","authors":"Carlos E Scorza, Aline G Aun, Júlia L Guedes, Maria Vitória Destro, Márjorie A Golim, Leandro G Braz, Mariana G Braz","doi":"10.1093/mutage/geaf005","DOIUrl":"10.1093/mutage/geaf005","url":null,"abstract":"<p><p>The objective of this longitudinal study was to jointly assess DNA damage, apoptosis, inflammatory marker levels, and white blood cell (WBC) counts in physicians occupationally exposed to inhalation anesthetics during specializations. Thus, we aimed to identify a possible cause-effect relationship between occupational exposure to waste anesthetic gases (WAGs), which were measured, and genotoxic, cytotoxic, and immunotoxic effects. Nineteen medical residents were evaluated at four time points: before entering medical residency (baseline) and at the beginning, middle, and end of medical residency. Peripheral blood mononuclear cells (PBMCs) were investigated for DNA damage, which was detected via the comet assay, and for apoptosis, which was detected via an annexin marker (flow cytometry). High-sensitivity C-reactive protein and serum inflammatory cytokines were evaluated via flow cytometry, and total and differential WBCs were counted. In addition, the concentrations of the WAGs measured in the workplace during the study were evaluated via an infrared spectrophotometer. The WAG concentrations were far higher than the internationally recommended values. Compared with those at previous time points, we observed increased DNA damage (P = .008) and apoptosis (P = .001) in PBMCs from the middle to the end of medical residency. Significant increases (P < .05) in the IL-8, IL-10, IL-12p70, IL-17A, IL-18, and IL-23 levels throughout medical residency were detected. There was no effect on the WBC count (P < .05), and all the means were within the reference range values. Occupational exposure to high levels of WAGs induces DNA damage, apoptosis, and changes in serum inflammatory marker levels, but not in leukocyte counts, in physicians who work in surgical theaters lacking an adequate scavenging system during medical residency.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":"489-497"},"PeriodicalIF":4.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476797","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":"N-nitrosamines: in silico modelling of DNA reactivity and identification of metabolic precursors.","authors":"Hristiana Ivanova, Petko I Petkov, Sunil Kulkarni, Tara Barton-Maclaren, Elena Kaloyanova, Stefan Kotov, Kalin Kirilov, Terry W Schultz, Ovanes G Mekenyan","doi":"10.1093/mutage/geaf009","DOIUrl":"10.1093/mutage/geaf009","url":null,"abstract":"<p><p>The discovery of N-nitrosamines (NNAs) as impurities in several pharmaceuticals has renewed activities in assessing their mutagenic and carcinogenic potential. In the current investigation, the binary mutagenic potential of NNAs is re-investigated using the mechanism-based structure-activity approach of the TIMES models. Emphasis is placed on meeting the OECD (Q)SAR principles for model validation and the organization's (Q)SAR prediction principles. A curated data set of 41 small and complex NNA-containing substances tested in a standard battery of Salmonella typhimurium strains with and without rat microsomal activation was assessed for these tasks. Structural boundaries are initially derived from activating mechanisms for interactions of parent NNAs with DNA described in the literature. These activating mechanisms include direct-acting mutagenicity (denitrosation of parent molecules) or DNA interactions after S9 metabolic activation (alpha-hydroxylation). After analysis of the 41 NNAs, structural features that mitigate or 'mask' the covalent binding of NNAs to DNA expanded the original alert definition. The structural fragments' predictive capabilities (performance) for the activating and negating mechanisms of these 41 chemicals are excellent. Three false positives and no false negatives are reported. Moreover, the role of metabolism in the N-nitrosation of secondary amines and tertiary amines after conversion to secondary amines under in vivo conditions is explained with descriptions of new metabolic transformations. These transformation boundaries are applied to different inventories to search for parent structures that are potential in vivo metabolic precursors of NNAs.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":"512-525"},"PeriodicalIF":4.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584368","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":"Global DNA methylation and its association with genetic instability and exposure to inorganic elements and polycyclic aromatic hydrocarbons in coal mining dust.","authors":"Grethel León-Mejía, Monica Cappetta, Ana Letícia Hilário Garcia, Ornella Fiorillo-Moreno, Paula Rohr, Amner Muñoz-Acevedo, Alvaro Miranda-Guevara, Milton Quintana-Sosa, Wilner Martinez-Lopez, João Antonio Pêgas Henriques, Juliana da Silva","doi":"10.1093/mutage/geaf010","DOIUrl":"10.1093/mutage/geaf010","url":null,"abstract":"<p><p>Coal mining has significant economic and environmental implications. The extraction and combustion of coal release harmful chemicals and dust, impacting air, soil, and water quality, as well as natural habitats and human health. This study aimed to investigate the association between global DNA methylation, DNA damage biomarkers (including telomere length), and inorganic element concentrations in the blood of individuals exposed to coal mining dust. Additionally, polycyclic aromatic hydrocarbons were analyzed. The study included 150 individuals exposed to coal mining and 120 unexposed controls. Results showed significantly higher global DNA hypermethylation in the exposed group compared to controls. Moreover, in the exposed group, micronucleus frequency and age showed a significant correlation with global DNA hypermethylation. Blood levels of inorganic elements, including titanium, phosphorus, sodium, aluminum, iron, sulfur, copper, chromium, zinc, chlorine, calcium, and potassium, were potentially associated with DNA methylation and oxidative damage, as indicated by comet assay results. Furthermore, exposure to polycyclic aromatic hydrocarbons such as fluoranthene, naphthalene, and anthracene, emitted in mining particulate matter, may contribute to these effects. These findings highlight the complex interplay between genetic instability, global DNA hypermethylation, and environmental exposure in coal mining areas, emphasizing the urgent need for effective mitigation strategies.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":"480-488"},"PeriodicalIF":4.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029954","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":"Carcinogenic parasites: insights into the epidemiology and possible mechanisms of cancer.","authors":"Shabir Ahmad Rather, Zahoor Ahmad Wani, Rashaid Ali Mustafa, Pooja Bharti, Rukhsana Kousar, Mohammad Vikas Ashraf, Shoeb Ahmad, A A Shah, M A Hannan Khan","doi":"10.1093/mutage/geaf007","DOIUrl":"10.1093/mutage/geaf007","url":null,"abstract":"<p><p>Naturally, a wide range of genetic and environmental variables predominate, such as bacterial, viral, and parasite infective entities that have been identified as carcinogenic bioagents. Many helminth and protozoan parasitic diseases are liable to cause human cancer. Conveniently, three trematode parasites viz. Schistosoma haematobium, Opisthorchis viverrini, and Clonorchis sinensis have been reported to be intrinsically linked with human cancer. Similar studies for other parasitic infections are still imprecise and need further validation. Plasmodium falciparum is known to cause holoendemic Burkitt lymphoma despite the non-carcinogenic role of malaria. This review is endowed with a coupled correlation and underlying mechanisms by which parasitic infections lead to carcinogenicity. An empirical documentation covering the prevalence and incidence of viral, bacterial, and parasitic carcinogenicity is illustrated in this article. Moreover, some probable diagnostic and treatment procedures for parasitic carcinogenicity are also summarized. A detailed account of various mutational and genetic changes that lead to carcinogenesis via different pathways is appended in this article.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":"465-479"},"PeriodicalIF":4.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605727","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":"Influence of pH and lysis duration on DNA damage detection: a Comparison of neutral and alkaline comet assays.","authors":"Ruzica Pribakovic, Julia Bornhorst, Helga Stopper, Ezgi Eyluel Bankoglu","doi":"10.1093/mutage/geaf019","DOIUrl":"https://doi.org/10.1093/mutage/geaf019","url":null,"abstract":"<p><p>The comet assay is a widely used method for measuring DNA damage and DNA repair. When DNA strand breaks happen, the supercoiling of DNA is relaxed and after alkaline or neutral electrophoresis, depending on the type of performed comet assay, DNA moves towards the anode, forming a comet tail. Thus, with increasing frequency of DNA strand breaks, an increase in the percentage of DNA in the tail is observed. The aim of this study was to compare systematically various steps like lysis, duration of electrophoresis and pH of the electrophoresis solution and their effect on the comet tail with regard to sensitivity for detection and quantification of DNA damage. We treated human lymphoblastoid TK6 cells with known genotoxic substances with a different mode of action and then performed both standard and modified alkaline and neutral comet assays. The Modifications included Fpg- and MspI-modified comet assays. Several aspects of this comparison are investigated for the first time here. The results obtained from these experiments showed a higher %DNA in tail in the alkaline comet assay compared to the neutral comet assay. Additionally, the lysis step was not critical in the alkaline comet assay, whereas it was essential for the neutral comet assay. Results from alkaline Fpg modified comet assay showed higher sensitivity in detecting single strand breaks and the neutral MspI modified comet assay was better in detecting DNA double strand breaks. Overall, our findings provided valuable insight into the differences between alkaline and neutral electrophoresis conditions in the comet assay and indicated that the alkaline comet assay is more sensitive for measuring total DNA damage.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961848","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":"Retraction to: Divergent molecular profile of PIK3CA gene in arsenic-associated bladder carcinoma.","authors":"","doi":"10.1093/mutage/geaf017","DOIUrl":"https://doi.org/10.1093/mutage/geaf017","url":null,"abstract":"","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961856","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 Micronucleus Assay in Exfoliated Buccal Cells for Occupational Exposure Studies: An Overview.","authors":"G Wultsch, A Nersesyan, M Mišík, F Ferk, K Schelch, M Scharnagl, M Grusch, S Knasmüller","doi":"10.1093/mutage/geaf018","DOIUrl":"https://doi.org/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 was realized 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 the last years and a recent correlation analyses with data from MN studies with lymphocytes indicate that the method is useful for the prediction of 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-non-specific) stains. The most pronounced effects were seen in metal production workers, miners, petrol station attendants, agricultural workers and pathologists. The sampling of the cells from the oral cavity is non-invasive and 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":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing the power of an advanced in vitro 3D liver model and error-corrected duplex sequencing for the detection of mutational signatures.","authors":"Gillian E Conway, Bérénice Chavanel, François Virard, Ume-Kulsoom Shah, Michael J Burgum, Stephen J Evans, Michael Korenjak, Laura E Thomas, Gareth J Jenkins, Jiri Zavadil, Shareen H Doak","doi":"10.1093/mutage/geaf015","DOIUrl":"https://doi.org/10.1093/mutage/geaf015","url":null,"abstract":"<p><p>Genotoxicity testing plays a crucial role in evaluating the hazards posed by various chemicals. Traditional methods, such as the Ames test, mammalian cell mutation assays and the transgenic rodent assay have certain limitations including laborious procedures and/or reliance on animal models. The aim of this study was to determine the potential of using error-corrected next-generation sequencing (ecNGS), specifically duplex sequencing (DS), as an alternative method for the detection of point mutations in conjunction with advanced in vitro models. This study establishes an easy to use, adaptable in vitro 3D HepG2 model, that shows good viability, and liver functionality over 14 days. 3D HepG2 spheroids were exposed to aristolochic acid in a repeated dose regime over 4 days. This was shown to significantly induce micronucleus formation, indicative of fixed DNA damage, in a dose dependent fashion. DS coupled with mutational signature analyses revealed a predominant treatment-specific T:A > A:T-enriched mutational signature explained by COSMIC signature SBS22 derived from human cancers associated with aristolochic acid exposure. De novo extraction provided a stable signature, of which more than 40% were unambiguously explained by SBS22 These results demonstrate that the presented 3D HepG2 spheroid model is appropriate for assessing chemically induced fixed DNA damage. Additionally, we provide evidence that DS applied to the studied in vitro 3D model has the capacity to reveal specific mutational signatures of mutagenic exposures. The modern integrative approach will improve the understanding of mechanisms of carcinogenesis related to chemical exposures by providing a cost-effective and efficient means to assess genotoxicity and mutagenicity. With the inclusion of mutational signature analyses, this approach would see a reduction in reliance on animal models and enhancement of hazard assessment accuracy.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835782","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}