Mutation research. Genetic toxicology and environmental mutagenesis最新文献

{"title":"Analysis of the trends in in vitro studies of the Latin America-Comet assay (LA-COMET) Group","authors":"Mahara Valverde ,&nbsp;Ana Rosa Flores-Márquez ,&nbsp;Sandra Gómez-Arroyo ,&nbsp;Laura Lafon-Hughes ,&nbsp;Grethel León-Mejía ,&nbsp;Diana M. Narváez ,&nbsp;Sonia Soloneski ,&nbsp;Noemi Tirado ,&nbsp;Juliana Da Silva ,&nbsp;Guillermo Espinosa-Reyes ,&nbsp;Deidamia Franco ,&nbsp;Ana Leticia García ,&nbsp;Patricia Mussali-Galante ,&nbsp;Elda Pacheco-Pantoja ,&nbsp;Gisela Poletta ,&nbsp;Celeste Ruiz de Arcaute ,&nbsp;María Fernanda Simoniello ,&nbsp;Efraín Tovar-Sánchez ,&nbsp;Leticia Yáñez- Estrada ,&nbsp;Emilio Rojas","doi":"10.1016/j.mrgentox.2026.503939","DOIUrl":"10.1016/j.mrgentox.2026.503939","url":null,"abstract":"<div><div>On a global scale, the versatility and high sensitivity of the comet assay have promoted its use from different perspectives to determine genotoxic damage. With this in mind and through the formation of a Latin American group denominated \"LA-COMET\", a review of the manuscripts published by the group is proposed from the perspective of <em>in vitro</em> studies, using the alkaline comet assay. To facilitate the analysis of the 81 manuscripts published between 1996 and 2022, they were classified into four categories based on the type of agents evaluated by the assay: 1) environmental pollutants; 2) pesticides and their mixtures; 3) radiation and drugs; and 4) natural products. The objective of this review was to describe the strengths and versatility of <em>in vitro</em> studies reflected by cellular models, putative DNA damaging agents, and the use of specific enzymes to identify particular DNA lesions. In addition, an <em>in vitro</em> QS (quality score) was established, taking into consideration the data provided in the publications regarding the cellular model, the method of disaggregation and the cell suspension obtention. Other considerations included the clarity of the description of the treatments, the use of negative and positive reference controls, and the use of specific enzymes and/or the functional evaluation of DNA repair. The analysis demonstrated that the publications of the LA-COMET group of <em>in vitro</em> models exhibited a high score with respect to the important parameters established in the OECD agreements.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"912 ","pages":"Article 503939"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147952729","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":"LA-COMET group: In vivo application of the comet assay in animal and plant models, including wild species","authors":"Gisela L. Poletta ,&nbsp;Patricia Mussali-Galante ,&nbsp;J. Alfredo Castillo-Ipiña ,&nbsp;Guillermo Espinosa-Reyes ,&nbsp;Ana Rosa Flores-Márquez ,&nbsp;Donaji J. González-Mille ,&nbsp;César A. Ilizaliturri-Hernández ,&nbsp;Celeste Ruiz de Arcaute ,&nbsp;Efraín Tovar-Sánchez ,&nbsp;Juliana da Silva ,&nbsp;Deidamia Franco ,&nbsp;Ana Leticia García ,&nbsp;Laura Lafon-Hughes ,&nbsp;Grethel León-Mejía ,&nbsp;Diana M. Narváez ,&nbsp;Elda Leonor Pacheco-Pantoja ,&nbsp;Emilio Rojas ,&nbsp;María Fernanda Simoniello ,&nbsp;Sonia Soloneski ,&nbsp;Noemi Tirado ,&nbsp;Sandra Gómez-Arroyo","doi":"10.1016/j.mrgentox.2026.503943","DOIUrl":"10.1016/j.mrgentox.2026.503943","url":null,"abstract":"<div><div>This paper is part of a series of publications developed by the Latin America-Comet assay (LA-COMET) group, which emerged in 2021, during the Asociacion Latinoamericana de Mutagenesis, Carcinogenesis y Teratogenesis Ambiental Congress, to organize the LA-COMET initiative. A total of 104 alkaline comet assay publications in animal (aquatic and terrestrial) and plant models, authored by members of this group, were analyzed to determine how DNA damage under experimental and environmental exposure conditions is assessed. The manuscript reflects the broad use and versatility of the comet assay in diverse taxonomic groups (invertebrates and vertebrates), <em>in vivo</em> research models, and cell types (e.g., erythrocytes, branchia cells, retinal epithelial cells, peripheral blood, liver, kidney, lung, bone marrow, testicle and nasal cells). Application of the comet assay in diverse biological systems requires careful methodological standardization to ensure reproducibility and allow for comparability of results. In order to unify the evaluations of the papers, a quality score system was developed, the ‘quality score comet assay’ (QSca), providing values reflecting the methodological rigor of the execution of the assay. The group identified key elements when performing the comet assay and uses them as the focus for the QSca score. The LA-COMET initiative will provide opportunities to strengthen collaborative networks among Latin American countries, promoting more integrative and regionally connected research where the comet assay can be used as a reliable and reproducible tool for the assessment of DNA damage in diverse biological models.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"912 ","pages":"Article 503943"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147992046","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":"In vivo evaluation of cisplatin(IV) conjugated to iron oxide adipate/tartrate nanoparticles using Drosophila melanogaster","authors":"A. Rodríguez Pescador ,&nbsp;C. López Portugués ,&nbsp;M. Montes-Bayón ,&nbsp;E. Blanco González ,&nbsp;L.M. Sierra","doi":"10.1016/j.mrgentox.2026.503935","DOIUrl":"10.1016/j.mrgentox.2026.503935","url":null,"abstract":"<div><div>Cisplatin and its analogues are a cornerstone of cancer chemotherapy; however, their therapeutic potential is limited by severe side effects and the development of drug resistance. To address these issues, nanocarriers and/or platinum prodrugs are being evaluated. Previous <em>in vitro</em> studies showed that ultra-small (&lt; 5 nm) iron oxide nanoparticles coated with tartaric and adipic acids (FeAT-NPs) are an efficient delivery system for the cisplatin prodrug cis-diamminetetrachloroplatinum(IV) (cisplatin(IV)). In this study, the <em>in vivo</em> behavior of cisplatin (IV) conjugated with the FeAT-NPs (FeAT-NPs-Pt(IV)) was evaluated using <em>Drosophila melanogaster</em> as a preliminary non-mammalian animal model. The resulting FeAT-NPs-Pt(IV) nanoconjugate was compared to free cisplatin and cisplatin(IV) regarding platinum incorporation into DNA, measured using inductively coupled plasma mass spectrometry (ICP-MS), as well as toxicity and genotoxicity, which were assessed using the alkaline comet and the <em>w/w</em>^<em>+</em> eye-spot SMART assays. Results revealed that the nanoconjugate achieved over eightfold higher DNA platination than free cisplatin, which is consistent with efficient cellular uptake and the subsequent intracellular release and activation of the prodrug. Despite this high platination, the nanoconjugate induced DNA strand-break levels similar to cisplatin and lower mutation and recombination frequencies than both cisplatin and cisplatin(IV), in both nucleotide excision repair (NER) efficient and deficient conditions. No significant toxicity was detected at the tested concentrations. These findings suggest that, <em>in vivo</em>, FeAT-NPs-Pt(IV) acts as an effective delivery system, potentially enabling the slow intracellular formation of active cisplatin. This would increase bioavailability to its target (DNA), while maintaining a significantly lower genotoxic stress profile compared to free cisplatin. Nonetheless, additional studies in tumor mammalian models are required to further explore these observations.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"912 ","pages":"Article 503935"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147800208","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":"An evaluation of common pharmaceutical solvents in the in vitro micronucleus assay","authors":"Jessica Noteboom ,&nbsp;Robert Smith ,&nbsp;Abigail Feiner ,&nbsp;Harry Bridges ,&nbsp;Siret Saaremagi ,&nbsp;Robert Jolly","doi":"10.1016/j.mrgentox.2026.503932","DOIUrl":"10.1016/j.mrgentox.2026.503932","url":null,"abstract":"<div><div>The in vitro micronucleus (IVMN) assay is a genetic toxicity assay routinely conducted in early drug development to evaluate clastogenicity and aneugenicity. At this discovery stage, synthetic routes for potential active pharmaceutical ingredients (API) are not optimized, which can lead to incomplete purification or solvation. API in genetic toxicity screens often contain residual solvent(s) in higher quantities than will be present in the GMP material. Understanding when solvents used either in API synthesis or as a vehicle may interfere with genetic toxicity screening results of APIs is important. In this work, twenty solvents commonly used in API synthesis were analyzed in the IVMN assay. These twenty solvents include acetonitrile, formic acid, anisole, dichloromethane, heptane, isopropyl amine, dimethyl sulfoxide, sodium hexafluorophosphate, N,N-Dimethylethylamine, N,N-Dimethylformamide, cyclopentyl methyl ether, 2-propanol, 1-butanol, 1-Methyl-2-pyrrolidinone, methanol, tetrahydrofuran, 2-Methyltetrahydrofuran, ethyl acetate, trifluoroacetic acid, and 2,6-Di-tert-butyl-4-methylphenol. When the in vitro data was correlated to available in vivo genotoxicity data published in the literature, only 5 of the 14 positively correlated. However, when a 10 mM limit of exposure was applied to the solvents, 13 of the 14 correlated to the in vivo literature results. While the results do not consider vehicle interaction within the assay, the data demonstrates that residual solvent carryover from API or other sources is generally not of concern. The 10 mM limit also reduces the false-positive risk of this assay. Baseline cytotoxicity and micronucleus formation from the solvents in this system provide a ranking on which solvents may produce confounding results in the assay.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"912 ","pages":"Article 503932"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147800209","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":"Micro- and nanoplastics as vectors of aquatic pollutants and genotoxicity: An integrated review across aquatic and mammalian systems with special reference to the scenario in India","authors":"Nuzhat Parveen ,&nbsp;Mohammad Abdulkader Akbarsha ,&nbsp;G.G.H.A. Shadab","doi":"10.1016/j.mrgentox.2026.503945","DOIUrl":"10.1016/j.mrgentox.2026.503945","url":null,"abstract":"<div><div>Microplastics (MPs) and nanoplastics (NPs) are environmental pollutants with paramount implications for aquatic ecosystems and, through that route, human health, particularly due to their oxidative stress-mediated genotoxic potential. This review is a synthesis of findings from recent studies, with emphasis on the scenario in India, on the bioavailability, toxicological risks, and cellular mechanisms of MPs and NPs (MNPs) in various organisms, separately addressing evidence from aquatic models, including marine mussels, common carp, zebrafish, rotifers, etc., and mammalian systems relying essentially on <em>in vitro</em> studies. Key evidence indicates that MPs adsorb persistent organic pollutants like Polycyclic Aromatic Hydrocarbons (PAHs), enhancing their bioavailability and inducing oxidative stress, immunological alterations, and developmental toxicity, which are closely associated with DNA damage and chromosome instability. As regards aquatic organisms, combined exposure to MPs and heavy metals to fish models exacerbates biochemical disruptions and immune suppression, along with oxidative stress–linked genotoxic responses such as DNA strand breaks and micronucleus formation. Zebrafish embryos exhibit microcirculation dysfunction and pathological angiogenesis upon NP exposure. Mammalian cell studies reveal size-dependent cytotoxicity, with smaller NPs causing greater oxidative damage and membrane disruption, which triggers mitochondrial dysfunction, excessive ROS production, cell-cycle arrest, and activation of DNA damage response pathways, evidenced by micronucleus formation, chromosomal abnormalities, and oxidative DNA lesions. Overall, toxicity is influenced by particle size, charge and co-contaminants, with oxidative stress emerging as the central mechanism that connects cellular toxicity to genetic damage. This review underscores the urgent need for integrated, multidisciplinary approaches to assess the environmental and toxicological risks of MNPs with special emphasis on standardized genotoxicity assessment, while informing regulatory and mitigation strategies for the future.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"912 ","pages":"Article 503945"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148167939","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":"Evaluation and interpretation of chemical genotoxicity risks; Strategies for method development","authors":"Makoto Hayashi","doi":"10.1016/j.mrgentox.2026.503938","DOIUrl":"10.1016/j.mrgentox.2026.503938","url":null,"abstract":"<div><div>Chemical toxicity is a major health concern. Extensive efforts have been made to reduce human exposure to harmful substances and genotoxicity is evaluated as one component of the overall human-safety assessment of chemicals. Many toxicology tests are conducted on experimental animals (<em>in vivo</em>) or cell lines (<em>in vitro</em>). The outcomes of these tests are extrapolated to assess hazards to humans. Many <em>in vitro</em> genotoxicity assays have been developed for hazard identification; however, the field is undergoing a significant shift from hazard identification toward risk assessment. Also, strategies are shifting from reliance on empirical <em>in vivo</em> and <em>in vitro</em> data toward the identification of toxicity mechanisms. Thus, new approaches are being explored to improve our understanding of genotoxicity mechanisms and their relevance in humans. The determination of genotoxic risk thresholds, in relation to cancer risk, is critical for human safety assessment. Risks should be neither overestimated nor underestimated. It is also necessary to consider the balance between risks and benefits of specific chemical substances.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"912 ","pages":"Article 503938"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148211917","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":"Response to \"Letter to the Editor; Re. Emiroğlu and Çeli̇k, “Radiology personnel chronically exposed to low-dose ionizing radiation: Assessment of genotoxic damage with the buccal micronucleus cytome assay”","authors":"Tülay Aşkın Çelik","doi":"10.1016/j.mrgentox.2026.503937","DOIUrl":"10.1016/j.mrgentox.2026.503937","url":null,"abstract":"","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"912 ","pages":"Article 503937"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147952728","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":"Letter to the Editor; Re. Emiroğlu and Çeli̇k, “Radiology personnel chronically exposed to low-dose ionizing radiation: Assessment of genotoxic damage with the buccal micronucleus cytome assay”","authors":"Armen K. Nersesyan","doi":"10.1016/j.mrgentox.2026.503936","DOIUrl":"10.1016/j.mrgentox.2026.503936","url":null,"abstract":"","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"912 ","pages":"Article 503936"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147852018","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 notice to “Levothyroxine synthesis impurities are neither mutagenic nor genotoxic: Insilico, Ames test and micronucleus test studies” [Mutat. Res. - Genet. Toxicol. Environ. Mutagenesis 898 (2024) 503796]","authors":"Rajesh Rane ,&nbsp;Akshay Prabhune ,&nbsp;Dileep Kumar ,&nbsp;Ajay Kumar ,&nbsp;Madhur Sewlikar ,&nbsp;Mugdha Suryawanshi ,&nbsp;Bharat Satpute ,&nbsp;Bapu Gawade ,&nbsp;Sachin Sakat","doi":"10.1016/j.mrgentox.2026.503929","DOIUrl":"10.1016/j.mrgentox.2026.503929","url":null,"abstract":"","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"911 ","pages":"Article 503929"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147656186","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":"Dimethyl itaconate mitigates diabetes-induced germ cell damage in rats by modulating p-NF-κB p65, Nrf2, DNA damage and restoration of antioxidant levels","authors":"Asutosh Pattnaik,&nbsp;Girija Prasanna Sahoo,&nbsp;Gopabandhu Jena","doi":"10.1016/j.mrgentox.2026.503919","DOIUrl":"10.1016/j.mrgentox.2026.503919","url":null,"abstract":"<div><div>Type 1 diabetes (T1DM), an autoimmune disease, is the result of damage to pancreatic beta cells, and causes prolonged hyperglycaemia. In males, diabetic hyperglycaemia can perturb sperm morphology and motility, reduce semen volume, and lower fertility. We have investigated the protective effects of dimethyl itaconate (DMI) on diabetes-induced germ cell damage in male SD rats. Diabetes was induced with streptozotocin and animals with blood glucose levels ≥ 250 mg/dL were included in the study. DMI was administered orally for four weeks. Testicular damage was evaluated by examining morphology, oxidative stress, inflammation, and hormonal levels. Diabetes increased oxidative stress (elevated MDA, reduced GSH levels), decreased sperm count and motility, and increased abnormal sperm morphology and fragmented sperm DNA. It also altered the expressions of key proteins in rat testes, including increased 8-OHdG, Caspase-3, p-NF-κB p65 and IL-6, and decreased 3β-HSD, Nrf2, HO-1 and SOD-1. DMI treatment significantly ameliorated these effects, demonstrating its protective role against diabetes-induced germ cell damage in rats.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"910 ","pages":"Article 503919"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980204","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}