Mutation research. Genetic toxicology and environmental mutagenesis最新文献

{"title":"Low dose X-radiation induced DNA damage and its association with Glandular dose in women undergoing mammography","authors":"Jivantika Daya Thejas ,&nbsp;Sanjna Vinod ,&nbsp;Divya K. Mohan ,&nbsp;Bhawna Dev ,&nbsp;Jai Prakash Srinivasan ,&nbsp;Venkateswarlu Raavi ,&nbsp;Venkatachalam Perumal","doi":"10.1016/j.mrgentox.2025.503856","DOIUrl":"10.1016/j.mrgentox.2025.503856","url":null,"abstract":"<div><div>Mammography is a widespread X-ray-based tool used for screening as well as early diagnosis of certain diseases related to breast tissue. However, the use of X-rays in mammography raised concern as a series of low-dose radiation exposures received during this procedure might increase health risks similar to high doses of acute exposure. To understand the effects of low-dose X-irradiation, blood samples were drawn from healthy volunteers (n = 5), X-irradiated <em>in vitro</em> with a dose similar to that obtained during mammography (2.5–3 mGy/plane), and also from women undergoing digital breast tomosynthesis imaging (before and after 1–2 h) (n = 18) were used as models. The level of induced DNA damage was determined using γ-H2AX foci and micronucleus (MN) formation in blood lymphocytes. In the <em>in vitro</em> irradiated samples, the mean γ-H2AX foci frequency in unirradiated control was 0.12 ± 0.03, and in irradiated samples was 0.25 ± 0.02 (p &lt; 0.0001). A similar increase in mean γ-H2AX foci frequency of 0.13 ± 0.01 and 0.21 ± 0.05 was observed before and after mammography imaging respectively (p &lt; 0.0001). A similar trend was observed for <em>in vitro</em> MN where the frequency was 0.0008 ± 0.0008 in unirradiated control and 0.0046 ± 0.0018 in irradiated samples (p &lt; 0.01). Whereas, a heterogeneous increase in MN frequency was observed in women who underwent mammography (p &lt; 0.001). Pearson correlation revealed a strong correlation between Average Glandular Dose (AGD) and γ-H2AX frequency (r²=0.7820) and a weak correlation between AGD and MN frequency (r²=0.0008). The present study suggests that the low doses of radiation from mammography imaging have the potential to induce early DNA damage and residual DNA damage observed until 72 h post-exposure; it might result in an increased risk for stochastic health effects during their lifetime<em>.</em></div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"902 ","pages":"Article 503856"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420942","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":"Micronuclei as genotoxicity endpoint applied in the co-culture of two mammalian cell lines","authors":"Naji Said Aboud Hadi ,&nbsp;Helga Stopper","doi":"10.1016/j.mrgentox.2024.503839","DOIUrl":"10.1016/j.mrgentox.2024.503839","url":null,"abstract":"<div><div>There has been a shift from traditional animal models towards alternative methods. While 2D cell culture has a decade long tradition, more advances methods like 3D cultures, organoids, and co-culture techniques, which better mimic in vivo conditions, are not yet well established in every research area. Genotoxicity assessment is an integral part of toxicological testing or regulatory approval of pharmaceuticals and chemicals. The micronucleus assay is now a standard method in this context. In this systematic literature review, we aim to describe the state of the art of the application of co-cultures of two mammalian cell lines for micronucleus assessment. We summarized the cell types used, methods for co-culture, disease models and agents, as well as the application of additional genotoxicity endpoints and viability tests. Airway system cells were the most frequent, followed by macrophage-like cells, liver cells, and various others. Co-culture techniques involve either direct physical contact or separation by porous membranes. Within a limited number of investigations using other genotoxicity assays like the comet and γH2AX assays in parallel, the micronucleus assay performed well. Overall, the micronucleus test demonstrating its suitability in disease models and for a more complex substance testing beyond simple 2D cultures, encouraging a more widespread use in co-culture systems in the future.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"901 ","pages":"Article 503839"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040311","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":"Cytotoxicity and genotoxicity of zinc oxide nanoparticles in human peripheral blood mononuclear cells","authors":"Jovanna Vanessa Ramos Angulo ,&nbsp;Juliana Fernández Valenzuela ,&nbsp;Sofía Isabel Freire-Bernal ,&nbsp;Victoria Eugenia Niño-Castaño ,&nbsp;Jorge Enrique Rodríguez Paez ,&nbsp;Rosa Amalia Dueñas-Cuellar","doi":"10.1016/j.mrgentox.2024.503838","DOIUrl":"10.1016/j.mrgentox.2024.503838","url":null,"abstract":"<div><div>Zinc oxide nanoparticles (ZnO-NPs) are of interest in biomedical applications, environmental remediation, and agriculture. ZnO-NPs inhibit the growth of phytopathogenic fungi and bacteria. We have evaluated their effects on mitochondrial function and the induction of membrane damage, apoptosis, and DNA damage in human peripheral blood mononuclear cells (PBMC) <em>in vitro</em>. ZnO-NPs caused significant reduction in cell viability and LDH release, indicating damage to cell membranes. Late apoptosis was significant and necrosis was significant at higher concentrations tested. ZnO-NPs did not induce micronucleus formation.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"901 ","pages":"Article 503838"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040302","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 silico and in vitro assessments of the mutagenicity of the azilsartan photoproduct","authors":"Takahiro Yoshikawa ,&nbsp;Naoto Hayashi ,&nbsp;Masayuki Yokota","doi":"10.1016/j.mrgentox.2024.503841","DOIUrl":"10.1016/j.mrgentox.2024.503841","url":null,"abstract":"<div><div>Photodegradation of azilsartan yields a phenanthridine derivative (APP). We suspected that APP could be a DNA-reactive substance, since many phenanthridine derivatives are mutagenic. In silico quantitative structure-activity relationship analysis indicated potential mutagenicity of APP, due to DNA reactivity at the 6-aminophenanthridine moiety. However, APP was not mutagenic in the Ames test. Density functional theory (DFT) calculations showed that APP cannot intercalate into DNA, due to its nonplanar structure, resulting from steric hindrance of its phenanthridine and benzimidazole moieties.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"901 ","pages":"Article 503841"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040305","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":"Cytogenetic markers in newborns of mothers with comorbidities","authors":"Aline C.B. Pinho ,&nbsp;Ana Beatriz M Baston ,&nbsp;Rita de Cássia F B Fontes ,&nbsp;Raquel A. Santos ,&nbsp;Marisa A.A. Brunherotti","doi":"10.1016/j.mrgentox.2024.503840","DOIUrl":"10.1016/j.mrgentox.2024.503840","url":null,"abstract":"<div><div>We have studied the presence and frequency of micronuclei in exfoliated oral mucosa cells of full-term newborns and their association with maternal prenatal factors. We report an analytical, observational, cross-sectional, prospective study that includes 97 preterm infants (&lt;37 weeks), 37 newborns from mothers with comorbidities, and 60 newborns from mothers without comorbidities, in a tertiary public hospital. Oral mucosa cells were collected within 24 h after birth. The frequency of cells with micronuclei and karyolytic cells was significantly higher in the group whose mothers had some form of comorbidity. Mothers with comorbidities had a shorter gestational age; the number of cells with micronuclei was higher in mothers with preterm premature rupture of membranes; and there were fewer karyolytic cells.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"901 ","pages":"Article 503840"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040301","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 transgenic MutaMouse hepatocyte mutation assay in vitro: Mutagenicity and mutation spectra of six substances with different mutagenic mechanisms","authors":"Alina Göpfert ,&nbsp;David M. Schuster ,&nbsp;Claudia Rülker ,&nbsp;Michael Eichenlaub ,&nbsp;Bogdan Tokovenko ,&nbsp;Martina Dammann ,&nbsp;Dorothee Funk-Weyer ,&nbsp;Naveed Honarvar ,&nbsp;Robert Landsiedel","doi":"10.1016/j.mrgentox.2024.503836","DOIUrl":"10.1016/j.mrgentox.2024.503836","url":null,"abstract":"<div><div>Mutagenicity testing is a component of the hazard assessment of industrial chemicals, biocides, and pesticides. Mutations induced by test substances can be detected by <em>in vitro</em> and <em>in vivo</em> methods that have been adopted as OECD Test Guidelines. One of these <em>in vivo</em> methods is the Transgenic Rodent Assay (TGRA), OECD test guideline no. 488. An analogous <em>in vitro</em> TGRA has been described, but experience with this test method is limited. In this study, six <em>in vivo</em> TGRA positive mutagens were tested in the <em>in vitro</em> TGRA based on primary MutaMouse hepatocytes. In addition to the functional read-out of the lacZ reporter gene, induced mutations were analysed by next-generation sequencing (NGS). Five of the six <em>in vivo</em> TGRA positive mutagens (N-ethyl-N-nitrosourea (ENU), ethyl methanesulfonate (EMS), mitomycin C (MMC), benzo[<em>a</em>]pyrene (B[<em>a</em>]P), and azathioprine (AZA), but not cyproterone acetate) mutated the lacZ gene <em>in vitro</em>. NGS identified mutations which matched the mutagenic mechanisms described in the literature. The alkylating agent ENU induced a greater proportion of A:T to T:A transversions than did the other alkylating agent, EMS, whereas EMS increased smaller deletions (1–4 bp). G:C to T:A transversions accounted for the majority of mutations identified after treatments with MMC and B[<em>a</em>]P, both of which form monoadducts at the guanine N2 position. AZA induced mainly G:C to A:T transitions, explained by the structural similarity of one of its metabolites to guanine. An increased proportion of mid-size changes (0.3–2.5 kb) was detected only for the crosslinking mutagen MMC. The <em>in vitro</em> TGRA based on primary MutaMouse hepatocytes is a promising <em>in vitro</em> assay for the assessment of mutation induction, reflecting many aspects of the corresponding <em>in vivo TGRA</em> and allowing for mutation spectra analysis to evaluate the induced mutations.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"901 ","pages":"Article 503836"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040313","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":"Investigation of genetic instability in patients with Diabetes Mellitus type I, II and LADA using buccal micronucleus cytome assay","authors":"G. Parsadanyan ,&nbsp;G. Zalinyan ,&nbsp;R. Markosyan ,&nbsp;M. Sarkisyan ,&nbsp;E. Aghajanova ,&nbsp;A. Sahakyan","doi":"10.1016/j.mrgentox.2024.503828","DOIUrl":"10.1016/j.mrgentox.2024.503828","url":null,"abstract":"<div><div>The aim of our pilot study was to investigate the frequency of micronuclei (MN) and other nuclear anomalies in exfoliated cells of the oral mucosa in patients with type I, II, and LADA (Latent Autoimmune Diabetes in Adults, classified as type 1.5 intermediate, slowly progressing diabetes) types of diabetes mellitus (DM) and compare them with healthy individuals of the Armenian population using the MN test. For each participant essential clinical and biochemical parameters were studied, including blood pressure, duration of illness, glycosylated hemoglobin (HbA1c), blood glucose, plasma glucose, urea, total protein, creatinine, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, HOMA-IR (insulin resistance), insulin, and triglycerides, as well as necessary anthropometric, genealogical, and genetic data. All participants were surveyed regarding habits that might affect MN levels, such as smoking, alcohol consumption, drug use, hereditary diseases, and viral infections. Cytogenetic analyses of exfoliated cells showed that the level of MN in exfoliated cells of DM patients was elevated approximately two to three times compared to healthy individuals. However, statistical significance was only reached in type I DM and LADA patients. The levels of other nuclear anomalies in the squamous epithelial cells of DM patients were also analyzed, and a significant increase in their levels was observed in all three DM types, indicating cytotoxic and genotoxic effects. The results of this study also revealed a high correlation between the total number of MN, cells with MN, blood glucose concentration, and glycosylated hemoglobin.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"900 ","pages":"Article 503828"},"PeriodicalIF":2.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142554162","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":"Disperse Red 1 azo dye: Consequences of low-dose/low-concentration exposures in mice and zebrafish","authors":"Fábio Henrique Fernandes ,&nbsp;Flávia Renata Abe ,&nbsp;Tamara Barbosa Gomes ,&nbsp;Cibele Borges dos Santos ,&nbsp;Wilma De Grava Kempinas ,&nbsp;Bianca Arruda Leite ,&nbsp;Danielle Palma de Oliveira ,&nbsp;Daisy Maria Fávero Salvadori","doi":"10.1016/j.mrgentox.2024.503830","DOIUrl":"10.1016/j.mrgentox.2024.503830","url":null,"abstract":"<div><div>Color Index Disperse Red 1 (DR1), an azo dye widely used in the textile industry and released into aquatic environments, is genotoxic in somatic cells, but little is known concerning its effects on the reproductive system or the early stages of embryonic development. We have assessed the effects on the spermatozoa of male mice following oral exposure to the dye, at low doses, for 14 days. Measured endpoints were DNA damage (comet assay), miRNA-34c levels, and sperm number, morphology, and motility. Exposure caused decreased miRNA-34c levels. We have also examined dye effects on zebrafish embryos and larvae, which included developmental impairment, altered glutathione transferase activity, and effects on reactive oxygen species and lipid peroxidation levels.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"900 ","pages":"Article 503830"},"PeriodicalIF":2.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142652770","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 vitro hepatic 3D cell models and their application in genetic toxicology: A systematic review","authors":"Martina Štampar,&nbsp;Bojana Žegura","doi":"10.1016/j.mrgentox.2024.503835","DOIUrl":"10.1016/j.mrgentox.2024.503835","url":null,"abstract":"<div><div>The rapid development of new chemicals and consumer products has raised concerns about their potential genotoxic effects on human health, including DNA damage leading to serious diseases. For such new chemicals and pharmaceutical products, international regulations require genotoxicity data, initially obtained through <em>in vitro</em> tests, followed by <em>in vivo</em> experiments, if needed. Traditionally, laboratory animals have been used for this purpose, however, they are costly, ethically problematic, and often unreliable due to species differences. Therefore, innovative more accurate <em>in vitro</em> testing approaches are rapidly being developed to replace, refine and reduce (3R) the use of animals for experimental purposes and to improve the relevance for humans in toxicology studies. One of such innovative approaches are <em>in vitro</em> three-dimensional (3D) cell models, which are already being highlighted as superior alternatives to the two-dimensional (2D) cell cultures that are traditionally used as <em>in vitro</em> models for the safety testing of chemicals and pharmaceuticals. 3D cell models provide physiologically relevant information and more predictive data for <em>in vivo</em> conditions. In the review article, we provide a comprehensive overview of 3D hepatic cell models, including HepG2, HepG2/C3A, HepaRG, human primary hepatocytes, and iPSC-derived hepatocytes, and their application in the field of genotoxicology. Through a detailed literature analysis, we identified 31 studies conducted between 2007 and April 2024 that used a variety of standard methods, such as the comet assay, the micronucleus assay, and the γH2AX assay, as well as new methodological approaches, including toxicogenomics, to assess the cytotoxic and genotoxic activity of chemicals, nanoparticles and natural toxins. Based on our search, we can conclude that the use of <em>in vitro</em> 3D cell models for genotoxicity testing has been increasing over the years and that 3D cell models have an even greater potential for future implementation and further refinement in genetic toxicology and risk assessment.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"900 ","pages":"Article 503835"},"PeriodicalIF":2.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142652699","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":"Bruce Nathan Ames: A scientist to remember (December 16, 1928—October 5, 2024)","authors":"David M. DeMarini","doi":"10.1016/j.mrgentox.2024.503832","DOIUrl":"10.1016/j.mrgentox.2024.503832","url":null,"abstract":"","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"900 ","pages":"Article 503832"},"PeriodicalIF":2.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746226","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}