Pub Date : 2026-01-23DOI: 10.1016/j.mrgentox.2026.503922
Tyago Henrique Alves Saraiva Cipriano , Jaqueline dos Santos Silva Pinheiro Rodrigues , Livia Caroline Alexandre de Araújo , Iago José Santos da Silva , Aleson Aparecido da Silva , Erima Maria de Amorim , Maria Gislaine Pereira , Lizandra Ferraz da Silva , Eduardo Henrique da Silva Melo , Amanda Alves de Araújo , Anadeje Celerino dos Santos Silva , Elvis Joacir De França , Maria Betânia Melo de Oliveira , Claudia Rohde
This study assessed the water quality of the Capibaribe River, a major water resource in the state of Pernambuco, Northeastern Brazil. In vivo toxicogenetic analyses were conducted using the Comet assay in Drosophila melanogaster, together with physicochemical assessments at four sampling points along the river. Genotoxicity analyses revealed a progressive increase in DNA damage that corresponded to the degree of urbanization along the river. The lowest Damage Index (DI) was recorded at point P1, in the municipality of Paudalho (DI = 35.67), an environmental protection area. The highest DI levels were observed along the two most urbanized stretches of Recife (DI = 68.67), at points P3 and P4. At these sites, concentrations of Total Dissolved Solids (TDS), chloride, sulfate, phosphate, and nitrate exceeded the limits set by the Brazilian National Council for the Environment (CONAMA). Additionally, elevated levels of sulfur (S), aluminum (Al), potassium (K), sodium (Na), phosphorus (P), and magnesium (Mg), elements known to cause genetic damage, were also detected. These findings underscore the importance of assessing genotoxic effects in model organisms, particularly in the more urbanized stretch of the Capibaribe River. They also highlight the urgent need for pollution control measures, continuous monitoring, and the implementation of strict environmental policies to safeguard both human and environmental health.
{"title":"In vivo genotoxicity and water quality assessment reveal urban influences on the Capibaribe River, Northeastern Brazil","authors":"Tyago Henrique Alves Saraiva Cipriano , Jaqueline dos Santos Silva Pinheiro Rodrigues , Livia Caroline Alexandre de Araújo , Iago José Santos da Silva , Aleson Aparecido da Silva , Erima Maria de Amorim , Maria Gislaine Pereira , Lizandra Ferraz da Silva , Eduardo Henrique da Silva Melo , Amanda Alves de Araújo , Anadeje Celerino dos Santos Silva , Elvis Joacir De França , Maria Betânia Melo de Oliveira , Claudia Rohde","doi":"10.1016/j.mrgentox.2026.503922","DOIUrl":"10.1016/j.mrgentox.2026.503922","url":null,"abstract":"<div><div>This study assessed the water quality of the Capibaribe River, a major water resource in the state of Pernambuco, Northeastern Brazil. <em>In vivo</em> toxicogenetic analyses were conducted using the Comet assay in <em>Drosophila melanogaster</em>, together with physicochemical assessments at four sampling points along the river. Genotoxicity analyses revealed a progressive increase in DNA damage that corresponded to the degree of urbanization along the river. The lowest Damage Index (DI) was recorded at point P1, in the municipality of Paudalho (DI = 35.67), an environmental protection area. The highest DI levels were observed along the two most urbanized stretches of Recife (DI = 68.67), at points P3 and P4. At these sites, concentrations of Total Dissolved Solids (TDS), chloride, sulfate, phosphate, and nitrate exceeded the limits set by the Brazilian National Council for the Environment (CONAMA). Additionally, elevated levels of sulfur (S), aluminum (Al), potassium (K), sodium (Na), phosphorus (P), and magnesium (Mg), elements known to cause genetic damage, were also detected. These findings underscore the importance of assessing genotoxic effects in model organisms, particularly in the more urbanized stretch of the Capibaribe River. They also highlight the urgent need for pollution control measures, continuous monitoring, and the implementation of strict environmental policies to safeguard both human and environmental health.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"910 ","pages":"Article 503922"},"PeriodicalIF":2.5,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024045","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}
Pub Date : 2026-01-16DOI: 10.1016/j.mrgentox.2026.503921
Emilio Rojas , Lucía Brito , Juliana Da Silva , Guillermo Espinosa-Reyes , Ana Rosa Flores-Márquez , Deidamia Franco , Ana Leticia García , Sandra Gómez-Arroyo , Cesar Arturo Ilizaliturri-Hernández , Laura Lafon-Hughes , Grethel León-Mejía , Mary Carmen Martinez , Patricia Mussali-Galante , Diana M. Narváez , Elda Leonor Pacheco-Pantoja , Gisela Laura Poletta , Celeste Ruiz de Arcaute , María Fernanda Simoniello , Sonia Soloneski , Noemi Tirado , Mahara Valverde
The comet assay is a versatile tool for evaluating DNA damage; its use has spread worldwide, including in Latin America. The LA-COMET group is a Latin American collaborative network. In a bibliometric study, we have analyzed 246 publications from seven countries, particularly with regard to topics addressed and impact. Quality scores (QSca) were assigned, based on the technical performance of the alkaline comet assay. Most (60 %) of the publications were scored with QSca 60 points out of 63 or better. Among the most common topics of interest are cancer, in vivo assays, DNA damage, pollution, and gene expression. We highlight the wide range of research topics, categorized into a) human monitoring studies; b) in vitro studies; and c) studies in animal and plant models. The LA-COMET group is encouraging collaborations, both within and beyond the group, to address topics of interest in genetic toxicology.
{"title":"The Latin America comet (LA-COMET) Group: A bibliometric study and quantitative analysis of the technical implementation of the alkaline comet assay","authors":"Emilio Rojas , Lucía Brito , Juliana Da Silva , Guillermo Espinosa-Reyes , Ana Rosa Flores-Márquez , Deidamia Franco , Ana Leticia García , Sandra Gómez-Arroyo , Cesar Arturo Ilizaliturri-Hernández , Laura Lafon-Hughes , Grethel León-Mejía , Mary Carmen Martinez , Patricia Mussali-Galante , Diana M. Narváez , Elda Leonor Pacheco-Pantoja , Gisela Laura Poletta , Celeste Ruiz de Arcaute , María Fernanda Simoniello , Sonia Soloneski , Noemi Tirado , Mahara Valverde","doi":"10.1016/j.mrgentox.2026.503921","DOIUrl":"10.1016/j.mrgentox.2026.503921","url":null,"abstract":"<div><div>The comet assay is a versatile tool for evaluating DNA damage; its use has spread worldwide, including in Latin America. The LA-COMET group is a Latin American collaborative network. In a bibliometric study, we have analyzed 246 publications from seven countries, particularly with regard to topics addressed and impact. Quality scores (QSca) were assigned, based on the technical performance of the alkaline comet assay. Most (60 %) of the publications were scored with QSca 60 points out of 63 or better. Among the most common topics of interest are cancer, in vivo assays, DNA damage, pollution, and gene expression. We highlight the wide range of research topics, categorized into a) human monitoring studies; b) in vitro studies; and c) studies in animal and plant models. The LA-COMET group is encouraging collaborations, both within and beyond the group, to address topics of interest in genetic toxicology.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"910 ","pages":"Article 503921"},"PeriodicalIF":2.5,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024037","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}
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.
{"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, Girija Prasanna Sahoo, 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":"2026-01-15","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}
Pub Date : 2026-01-13DOI: 10.1016/j.mrgentox.2026.503920
Wesley Rodrigues Soares , Thiarlen Marinho da Luz , Raíssa de Oliveira Ferreira , Letícia Paiva de Matos , Rafaela Ribeiro de Brito , Alex Gomes Rodrigues , Bruno da Cruz Pádua , Abraão Tiago Batista Guimarães , Aline Sueli de Lima Rodrigues , Guilherme Malafaia
The increasing dissemination of microplastics (MPs) in the environment and their potential adverse effects on human and animal health have raised significant concerns in the scientific community. In this context, we aimed to investigate the toxicity induced by polyethylene (PE) MPs in the blood of Swiss mice (Mus musculus), focusing on biomarkers of oxidative and nitrosative stress and genotoxicity. Thirty mice were distributed across three experimental groups: two groups intravenously inoculated with polyethylene MPs at target systemic blood concentrations of 7.1 µg/mL and 355 µg/mL, respectively, and a non-exposed control group. After five days of intravenous (single) exposure to MPs, analyses revealed particles in the blood, liver, and kidneys, indicating selective retention in these tissues. While the Comet assay demonstrated increased DNA damage in peripheral blood, corroborating the genotoxicity of MPs, biochemical analyses revealed a complex response that depended on the organ and the biomarker evaluated. In the liver, we observed a significant reduction in the oxidative stress index, a metric that integrates pro-oxidant parameters (ROS and MDA) in relation to the endogenous antioxidant activities of SOD and CAT. At the same time, in the kidneys, there was an increase in the ratio between SOD and CAT activity. In both organs, increased nitrite production suggests the induction of marked nitrosative stress. On the other hand, in the liver, MDA levels surprisingly decreased, suggesting that MPs may interfere with lipid peroxidation pathways or promote the diversion of ROS toward NO-mediated peroxynitrite formation, reducing classical lipid oxidative damage. Principal Component Analysis (PCA) and cluster analysis provided an exploratory and integrative overview of the dataset, revealing distinct biochemical patterns between the control and MP-exposed groups, with higher MP concentrations associated with more pronounced oxidative and genotoxic responses. Thus, we conclude that exposure to MPs can cause significant cellular damage, reinforcing the need for further research to understand the risks associated with MP contamination and to develop effective mitigation strategies.
{"title":"Microplastics in motion: Genotoxic and redox imbalance impacts of systemic exposure in a murine model","authors":"Wesley Rodrigues Soares , Thiarlen Marinho da Luz , Raíssa de Oliveira Ferreira , Letícia Paiva de Matos , Rafaela Ribeiro de Brito , Alex Gomes Rodrigues , Bruno da Cruz Pádua , Abraão Tiago Batista Guimarães , Aline Sueli de Lima Rodrigues , Guilherme Malafaia","doi":"10.1016/j.mrgentox.2026.503920","DOIUrl":"10.1016/j.mrgentox.2026.503920","url":null,"abstract":"<div><div>The increasing dissemination of microplastics (MPs) in the environment and their potential adverse effects on human and animal health have raised significant concerns in the scientific community. In this context, we aimed to investigate the toxicity induced by polyethylene (PE) MPs in the blood of Swiss mice (<em>Mus musculus</em>), focusing on biomarkers of oxidative and nitrosative stress and genotoxicity. Thirty mice were distributed across three experimental groups: two groups intravenously inoculated with polyethylene MPs at target systemic blood concentrations of 7.1 µg/mL and 355 µg/mL, respectively, and a non-exposed control group. After five days of intravenous (single) exposure to MPs, analyses revealed particles in the blood, liver, and kidneys, indicating selective retention in these tissues. While the Comet assay demonstrated increased DNA damage in peripheral blood, corroborating the genotoxicity of MPs, biochemical analyses revealed a complex response that depended on the organ and the biomarker evaluated. In the liver, we observed a significant reduction in the oxidative stress index, a metric that integrates pro-oxidant parameters (ROS and MDA) in relation to the endogenous antioxidant activities of SOD and CAT. At the same time, in the kidneys, there was an increase in the ratio between SOD and CAT activity. In both organs, increased nitrite production suggests the induction of marked nitrosative stress. On the other hand, in the liver, MDA levels surprisingly decreased, suggesting that MPs may interfere with lipid peroxidation pathways or promote the diversion of ROS toward NO-mediated peroxynitrite formation, reducing classical lipid oxidative damage. Principal Component Analysis (PCA) and cluster analysis provided an exploratory and integrative overview of the dataset, revealing distinct biochemical patterns between the control and MP-exposed groups, with higher MP concentrations associated with more pronounced oxidative and genotoxic responses<em>.</em> Thus, we conclude that exposure to MPs can cause significant cellular damage, reinforcing the need for further research to understand the risks associated with MP contamination and to develop effective mitigation strategies.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"910 ","pages":"Article 503920"},"PeriodicalIF":2.5,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980205","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}
Pub Date : 2026-01-08DOI: 10.1016/j.mrgentox.2025.503916
Matilde Matteoli , Aurora Falaschi , Chiara Naldoni , Domenica Di Bello , Francesca Ceccanti , Veronica Esposti , Barbara Pinto , Simona Piaggi , Roberto Scarpato
High Mobility Group Box 1 (HMGB1) plays a dual role in cell physiology: within the nucleus, it supports chromatin stabilization and DNA repair, while its translocation to the cytoplasm or release into the extracellular space triggers autophagy and inflammatory signaling. We have investigated how different environmental mutagens affect HMGB1 localization in two colorectal cancer cell lines, HCT116TP53 + /+ and HCT116TP53-/-. Cells were exposed to ultraviolet-A radiation (UV-A), blue light, 1,4-benzoquinone (BQ), or 1,2,3,4-diepoxybutane (DEB), under conditions permitting cell proliferation while inducing genotoxic stress. DNA damage, expressed as either double-strand breaks (DSBs) or chromosomal alterations, was evaluated by the γ-H2AX phosphorylation assay or the micronucleus (MN) test, respectively. UV-C radiation and mitomycin C (MMC) were used as positive controls. All agents significantly increased DSB formation and MN frequency in both p53-proficient and p53-deficient cells. Before treatment, HMGB1 was distributed between the nucleus and cytoplasm. After exposure to UV-A or blue light, the protein showed a pronounced cytoplasmic translocation, suggesting the activation of stress-induced inflammatory pathways. In contrast, exposure to BQ or DEB promoted strong nuclear retention of HMGB1, consistent with its role in DNA repair. Overall, these findings suggest that, in HCT116 tumor cells, HMGB1 localization is dynamically regulated according to the type and duration of genotoxic stress: physical mutagens favor cytoplasmic signaling responses while chemical mutagens reinforce nuclear repair mechanisms.
{"title":"Dynamic subcellular localization of HMGB1 in colorectal cancer cells following exposure to environmental mutagens","authors":"Matilde Matteoli , Aurora Falaschi , Chiara Naldoni , Domenica Di Bello , Francesca Ceccanti , Veronica Esposti , Barbara Pinto , Simona Piaggi , Roberto Scarpato","doi":"10.1016/j.mrgentox.2025.503916","DOIUrl":"10.1016/j.mrgentox.2025.503916","url":null,"abstract":"<div><div>High Mobility Group Box 1 (HMGB1) plays a dual role in cell physiology: within the nucleus, it supports chromatin stabilization and DNA repair, while its translocation to the cytoplasm or release into the extracellular space triggers autophagy and inflammatory signaling. We have investigated how different environmental mutagens affect HMGB1 localization in two colorectal cancer cell lines, HCT116<sup><em>TP53 + /+</em></sup> and HCT116<sup><em>TP53-/-</em></sup>. Cells were exposed to ultraviolet-A radiation (UV-A), blue light, 1,4-benzoquinone (BQ), or 1,2,3,4-diepoxybutane (DEB), under conditions permitting cell proliferation while inducing genotoxic stress. DNA damage, expressed as either double-strand breaks (DSBs) or chromosomal alterations, was evaluated by the γ-H2AX phosphorylation assay or the micronucleus (MN) test, respectively. UV-C radiation and mitomycin C (MMC) were used as positive controls. All agents significantly increased DSB formation and MN frequency in both p53-proficient and p53-deficient cells. Before treatment, HMGB1 was distributed between the nucleus and cytoplasm. After exposure to UV-A or blue light, the protein showed a pronounced cytoplasmic translocation, suggesting the activation of stress-induced inflammatory pathways. In contrast, exposure to BQ or DEB promoted strong nuclear retention of HMGB1, consistent with its role in DNA repair. Overall, these findings suggest that, in HCT116 tumor cells, HMGB1 localization is dynamically regulated according to the type and duration of genotoxic stress: physical mutagens favor cytoplasmic signaling responses while chemical mutagens reinforce nuclear repair mechanisms.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"910 ","pages":"Article 503916"},"PeriodicalIF":2.5,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145929214","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}
Pub Date : 2026-01-07DOI: 10.1016/j.mrgentox.2026.503918
Alina Goepfert , Patrick Heid , Denise Brandl , Daniela Kuhn , Bärbel Moos , Tais Meziara Wilson , Martina Dammann , Naveed Honarvar , Robert Landsiedel
This study combined an in vivo Transgenic Rodent Gene Mutation Assay (TGRA) and Mammalian Erythrocyte Micronucleus Test (MNT) using male MutaMouse to assess the four positive control substances recommended by the OECD test guideline no. 488: benzo[a]pyrene (B[a]P), N-ethyl-N-nitrosourea (ENU), 2,4-diaminotoluene (2,4-DAT), and ethyl carbamate (EC). The studies followed the procedures described in the OECD guidelines 488 and 474. Gene mutations were assessed in site-of-contact organs, glandular stomach and small intestine, as well as in the liver, and germ cells isolated from testes and cauda epididymis. Micronuclei were measured in peripheral blood reticulocytes by flow cytometry. B[a]P and ENU induced dose-dependent increases in gene mutations in somatic and germ cells, as well as significant increases in the micronucleus rate in peripheral blood reticulocytes. In contrast, 2,4-DAT and EC induced weak gene mutation responses in some somatic tissues, but no significant effects in germ cells. This highlights the tissue-specific responses and thus a need for differentiated assessments. All test substances induced an increase of micronuclei to different extents in peripheral blood reticulocytes. The combined TGRA-MNT protocol enabled comprehensive evaluation of gene mutation and micronucleus induction within the same study, supporting reduction in animal use for in vivo mutagenicity testing. B[a]P and ENU can be used as positive control substances for the combined TGRA-MNT approach.
本研究结合体内转基因啮齿动物基因突变试验（TGRA）和哺乳动物红细胞微核试验（MNT），利用雄性mutammouse评估经合组织（OECD）试验指南第1号推荐的4种阳性对照物质。488：苯并[a]芘（B[a]P）， n -乙基-n -亚硝基脲（ENU）， 2,4-二氨基甲苯（2,4- dat）和氨基甲酸乙酯（EC）。这些研究遵循经合发组织准则488和474所述的程序。基因突变在接触部位器官、腺胃和小肠、肝脏以及从睾丸和附睾尾分离的生殖细胞中进行了评估。用流式细胞术检测外周血网织细胞微核。B[a]P和ENU诱导体细胞和生殖细胞基因突变呈剂量依赖性增加，同时外周血网状细胞微核率显著增加。相比之下，2,4- dat和EC在一些体细胞组织中诱导了微弱的基因突变反应，但在生殖细胞中没有显著的影响。这突出了组织特异性反应，因此需要进行差异化评估。所有试验物质均不同程度地诱导外周血网织细胞微核升高。TGRA-MNT联合方案能够在同一研究中对基因突变和微核诱导进行综合评估，支持减少动物体内诱变试验。B[a]P和ENU可作为TGRA-MNT联合检测的阳性对照物质。
{"title":"Combined assessment of transgenic rodent gene mutation and micronuclei formation by benzo[a]pyrene, N-ethyl-N-nitrosourea, 2,4-diaminotoluene and ethyl carbamate","authors":"Alina Goepfert , Patrick Heid , Denise Brandl , Daniela Kuhn , Bärbel Moos , Tais Meziara Wilson , Martina Dammann , Naveed Honarvar , Robert Landsiedel","doi":"10.1016/j.mrgentox.2026.503918","DOIUrl":"10.1016/j.mrgentox.2026.503918","url":null,"abstract":"<div><div>This study combined an in vivo Transgenic Rodent Gene Mutation Assay (TGRA) and Mammalian Erythrocyte Micronucleus Test (MNT) using male MutaMouse to assess the four positive control substances recommended by the OECD test guideline no. 488: benzo[<em>a</em>]pyrene (B[<em>a</em>]P), N-ethyl-N-nitrosourea (ENU), 2,4-diaminotoluene (2,4-DAT), and ethyl carbamate (EC). The studies followed the procedures described in the OECD guidelines 488 and 474. Gene mutations were assessed in site-of-contact organs, glandular stomach and small intestine, as well as in the liver, and germ cells isolated from testes and cauda epididymis. Micronuclei were measured in peripheral blood reticulocytes by flow cytometry. B[<em>a</em>]P and ENU induced dose-dependent increases in gene mutations in somatic and germ cells, as well as significant increases in the micronucleus rate in peripheral blood reticulocytes. In contrast, 2,4-DAT and EC induced weak gene mutation responses in some somatic tissues, but no significant effects in germ cells. This highlights the tissue-specific responses and thus a need for differentiated assessments. All test substances induced an increase of micronuclei to different extents in peripheral blood reticulocytes. The combined TGRA-MNT protocol enabled comprehensive evaluation of gene mutation and micronucleus induction within the same study, supporting reduction in animal use for in vivo mutagenicity testing. B[<em>a</em>]P and ENU can be used as positive control substances for the combined TGRA-MNT approach.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"910 ","pages":"Article 503918"},"PeriodicalIF":2.5,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145915216","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}
Pub Date : 2025-12-23DOI: 10.1016/j.mrgentox.2025.503915
Gaiyan Du , Zhenxin Guo , Jingyi Wu , Junyan Zhang , Jing Wang , Huiqin Zhang , Fang Gao
Background
The cytokinesis-block micronucleus (CBMN) assay is widely used for biomonitoring populations exposed to ionizing radiation as a simpler alternative to the chromosomal aberration (CA) assay. However, evidence regarding the concordance of these two assays under chronic low-dose occupational exposure remains limited and inconsistent.
Objective
This study aimed to systematically evaluate the agreement and diagnostic performance of the micronucleus (MN) assay relative to the CA assay in a cohort of medical radiation workers chronically exposed to low doses.
Methods
In this cross-sectional study, we analyzed 1226 concurrent MN and CA test results from 321 medical radiation workers. Both assays were performed on the same blood sample from each participant in accordance with national standards (GBZ/T 248–2014; GBZ/T 328–2023). Agreement between the two assays was assessed using Cohen’s kappa statistic, and diagnostic performance (sensitivity, specificity, AUC) was assessed across MN thresholds ranging from 1 ‰ to 6 ‰.
Results
Although the MN and CA assays were statistically associated (χ² = 8.73, p = 0.003), their agreement was only slight (κ = 0.08). The MN assay showed poor diagnostic accuracy (AUC = 0.579). At the conventional 6 ‰ threshold, the MN assay demonstrated high specificity (91.2 %) and a high negative predictive value (NPV > 95 %), but very low sensitivity (19.7 %) and a low positive predictive value (PPV) of approximately 11 %.
Conclusion
The MN assay shows limited concordance and diagnostic accuracy compared with the CA assay under chronic low-dose exposure conditions and therefore cannot be recommended as a standalone substitute. However, its consistently high NPV supports its use as an efficient rule-out tool within a tiered surveillance strategy, where negative MN results reliably exclude CA-detectable chromosomal damage and positive results trigger confirmatory CA testing.
{"title":"Limited concordance between micronucleus and chromosomal aberration assays in medical radiation workers: Evidence from a tertiary hospital-based study","authors":"Gaiyan Du , Zhenxin Guo , Jingyi Wu , Junyan Zhang , Jing Wang , Huiqin Zhang , Fang Gao","doi":"10.1016/j.mrgentox.2025.503915","DOIUrl":"10.1016/j.mrgentox.2025.503915","url":null,"abstract":"<div><h3>Background</h3><div>The cytokinesis-block micronucleus (CBMN) assay is widely used for biomonitoring populations exposed to ionizing radiation as a simpler alternative to the chromosomal aberration (CA) assay. However, evidence regarding the concordance of these two assays under chronic low-dose occupational exposure remains limited and inconsistent.</div></div><div><h3>Objective</h3><div>This study aimed to systematically evaluate the agreement and diagnostic performance of the micronucleus (MN) assay relative to the CA assay in a cohort of medical radiation workers chronically exposed to low doses.</div></div><div><h3>Methods</h3><div>In this cross-sectional study, we analyzed 1226 concurrent MN and CA test results from 321 medical radiation workers. Both assays were performed on the same blood sample from each participant in accordance with national standards (GBZ/T 248–2014; GBZ/T 328–2023). Agreement between the two assays was assessed using Cohen’s kappa statistic, and diagnostic performance (sensitivity, specificity, AUC) was assessed across MN thresholds ranging from 1 ‰ to 6 ‰.</div></div><div><h3>Results</h3><div>Although the MN and CA assays were statistically associated (χ² = 8.73, p = 0.003), their agreement was only slight (κ = 0.08). The MN assay showed poor diagnostic accuracy (AUC = 0.579). At the conventional 6 ‰ threshold, the MN assay demonstrated high specificity (91.2 %) and a high negative predictive value (NPV > 95 %), but very low sensitivity (19.7 %) and a low positive predictive value (PPV) of approximately 11 %.</div></div><div><h3>Conclusion</h3><div>The MN assay shows limited concordance and diagnostic accuracy compared with the CA assay under chronic low-dose exposure conditions and therefore cannot be recommended as a standalone substitute. However, its consistently high NPV supports its use as an efficient rule-out tool within a tiered surveillance strategy, where negative MN results reliably exclude CA-detectable chromosomal damage and positive results trigger confirmatory CA testing.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"909 ","pages":"Article 503915"},"PeriodicalIF":2.5,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145840560","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}
Pub Date : 2025-12-17DOI: 10.1016/j.mrgentox.2025.503914
Rayssa Lima dos Santos , Mônica Lúcia Adam , Ednilza Maranhão dos Santos , Jozélia Maria de Sousa Correia , Paulo Sérgio Martins de Carvalho
Environmental contamination by heavy metals poses a significant threat to aquatic biodiversity, however, the genotoxic effects in reptiles remain poorly understood, particularly in tropical ecosystems. This study provides the first genotoxic assessment of Caiman latirostris in northeastern Brazil, integrating cytogenetic biomarkers and trace metal analysis. Twenty-eight individuals were sampled from three areas representing distinct levels of anthropogenic pressure: a preserved reference site (Farming Area - FA), a moderately impacted reservoir (Tapacura Reservoir - TR), and a highly urbanized area (Urban Area - UA). Micronucleus frequency (MNF) was significantly higher in specimens from UA compared to FA (Kruskal–Wallis, p < 0.001), indicating potential genotoxic effects associated with untreated urban effluents and metal exposure. Although no significant differences in nuclear anomalies frequency (NAF) were found among sites, a moderate positive correlation was observed between MNF and NAF (Spearman’s rho = 0.56; p = 0.026). MNF showed significant positive associations with blood concentrations of aluminum (p = 0.027), chromium (p = 0.049), iron (p = 0.035), manganese (p = 0.043), and zinc (p = 0.0083). Principal Component Analysis (PCA) confirmed these patterns, with MNF aligned along the same vector direction as Al and Cr, and opposed to Fe, Mn, Zn, and Pb, revealing distinct contamination profiles. No significant correlations were found between NAF and individual metals. These findings support the use of MNF and NAF as sensitive and complementary biomarkers for genotoxicity in reptiles. The integration of biomarker responses and multivariate analysis highlights C. latirostris as an effective sentinel species for environmental monitoring. This study provides novel baseline data on cytogenetic biomarkers in crocodilians from tropical freshwater ecosystems, underscoring the need for continued ecotoxicological monitoring in human-impacted areas.
{"title":"Integrated assessment of metal bioaccumulation and genotoxic biomarkers in blood of broad-snouted caiman (Caiman latirostris) from Northeastern Brazil","authors":"Rayssa Lima dos Santos , Mônica Lúcia Adam , Ednilza Maranhão dos Santos , Jozélia Maria de Sousa Correia , Paulo Sérgio Martins de Carvalho","doi":"10.1016/j.mrgentox.2025.503914","DOIUrl":"10.1016/j.mrgentox.2025.503914","url":null,"abstract":"<div><div>Environmental contamination by heavy metals poses a significant threat to aquatic biodiversity, however, the genotoxic effects in reptiles remain poorly understood, particularly in tropical ecosystems. This study provides the first genotoxic assessment of <em>Caiman latirostris</em> in northeastern Brazil, integrating cytogenetic biomarkers and trace metal analysis. Twenty-eight individuals were sampled from three areas representing distinct levels of anthropogenic pressure: a preserved reference site (Farming Area - FA), a moderately impacted reservoir (Tapacura Reservoir - TR), and a highly urbanized area (Urban Area - UA). Micronucleus frequency (MNF) was significantly higher in specimens from UA compared to FA (Kruskal–Wallis, p < 0.001), indicating potential genotoxic effects associated with untreated urban effluents and metal exposure. Although no significant differences in nuclear anomalies frequency (NAF) were found among sites, a moderate positive correlation was observed between MNF and NAF (Spearman’s <em>rho</em> = 0.56; p = 0.026). MNF showed significant positive associations with blood concentrations of aluminum (p = 0.027), chromium (p = 0.049), iron (p = 0.035), manganese (p = 0.043), and zinc (p = 0.0083). Principal Component Analysis (PCA) confirmed these patterns, with MNF aligned along the same vector direction as Al and Cr, and opposed to Fe, Mn, Zn, and Pb, revealing distinct contamination profiles. No significant correlations were found between NAF and individual metals. These findings support the use of MNF and NAF as sensitive and complementary biomarkers for genotoxicity in reptiles. The integration of biomarker responses and multivariate analysis highlights <em>C. latirostris</em> as an effective sentinel species for environmental monitoring. This study provides novel baseline data on cytogenetic biomarkers in crocodilians from tropical freshwater ecosystems, underscoring the need for continued ecotoxicological monitoring in human-impacted areas.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"909 ","pages":"Article 503914"},"PeriodicalIF":2.5,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145840479","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}
Pub Date : 2025-12-17DOI: 10.1016/j.mrgentox.2025.503913
Kajal Gaur , Yasir Hasan Siddique
Bis(2-ethylhexyl) phthalate (DEHP) is a widely used synthetic compound known for its significant environmental and health hazards. It is particularly recognized for disrupting cellular functions by interfering with endocrine activity and inducing oxidative stress. Our previous research established that DEHP causes both cytotoxic and genotoxic effects in third instar larvae of Drosophila melanogaster (hsp70-lacZ) Bg9. The present study explores the protective role of apigenin, a naturally occurring flavonoid, against DEHP-induced toxicity in the model organism. Apigenin was mixed into the larval diet at concentrations of 20, 40, 60, and 80 µM, alongside 0.02 M DEHP, and administered for 24 h. Our findings revealed that apigenin supplementation significantly reduced gut tissue damage, lowered Hsp70 expression, and decreased both the apoptotic index and DNA damage in third instar larvae exposed to DEHP. Apigenin effectively reduced the elevated activities of caspase-3 and caspase-9 induced by Bis(2-ethylhexyl) phthalate exposure. These results highlight apigenin’s potential as an effective protective agent against the toxic effects of DEHP.
邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种广泛使用的合成化合物，因其对环境和健康有重大危害而闻名。它特别被认为是通过干扰内分泌活动和诱导氧化应激来破坏细胞功能。我们之前的研究证实DEHP对黑腹果蝇（Drosophila melanogaster, hsp70-lacZ） Bg9三龄幼虫具有细胞毒性和基因毒性作用。本研究探讨了芹菜素（一种天然存在的类黄酮）对模型生物中dehp诱导的毒性的保护作用。将芹菜素以20、40、60和80µM的浓度与0.02 M DEHP混合到幼虫饲料中，并给予24 h。我们的研究结果表明，添加芹菜素可以显著减少DEHP暴露的3龄幼虫的肠道组织损伤，降低Hsp70的表达，降低凋亡指数和DNA损伤。芹菜素有效降低了邻苯二甲酸双（2-乙基己基）暴露引起的caspase-3和caspase-9活性升高。这些结果突出了芹菜素作为抗DEHP毒性作用的有效保护剂的潜力。
{"title":"Effect of apigenin against Bis(2-ethylhexyl) phthalate induced toxicity on Drosophila melanogaster","authors":"Kajal Gaur , Yasir Hasan Siddique","doi":"10.1016/j.mrgentox.2025.503913","DOIUrl":"10.1016/j.mrgentox.2025.503913","url":null,"abstract":"<div><div>Bis(2-ethylhexyl) phthalate (DEHP) is a widely used synthetic compound known for its significant environmental and health hazards. It is particularly recognized for disrupting cellular functions by interfering with endocrine activity and inducing oxidative stress. Our previous research established that DEHP causes both cytotoxic and genotoxic effects in third instar larvae of <em>Drosophila melanogaster (hsp70-lacZ) Bg</em><sup><em>9</em></sup>. The present study explores the protective role of apigenin, a naturally occurring flavonoid, against DEHP-induced toxicity in the model organism. Apigenin was mixed into the larval diet at concentrations of 20, 40, 60, and 80 µM, alongside 0.02 M DEHP, and administered for 24 h. Our findings revealed that apigenin supplementation significantly reduced gut tissue damage, lowered Hsp70 expression, and decreased both the apoptotic index and DNA damage in third instar larvae exposed to DEHP. Apigenin effectively reduced the elevated activities of caspase-3 and caspase-9 induced by Bis(2-ethylhexyl) phthalate exposure. These results highlight apigenin’s potential as an effective protective agent against the toxic effects of DEHP.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"909 ","pages":"Article 503913"},"PeriodicalIF":2.5,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788054","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}
Pub Date : 2025-12-13DOI: 10.1016/j.mrgentox.2025.503912
Ana María Palermo, Eliana Ruth Steinberg, Marta Dolores Mudry
Methanol (MeOH) is a colorless, flammable, poisonous, alcohol that causes intoxication by ingesting, inhaling or by contact with formulations that include it. It is produced in large volumes and there is high level of human exposure, especially by the inhalation route. It has been reported as innocuous in various test systems; thus, the aim of this work was to search for in vivo genotoxic effects of MeOH in Drosophila melanogaster, studying its ability to induce nondisjunction (ND) in females. Treatments were acute (60 min) and via inhalation. It was toxic in 1-day old flies (MI = 63 % for 75 % MeOH) and in 5-days old flies (MI = 8.4 %, 40 % MeOH). Female fertility was severely affected during the first 24 h after treatment, later control values were recovered. MeOH induced a 16-fold increase of ND (%) in 1-day old females, and a 9-fold rise in 5-days old female’s offspring, but control values were recovered in the offspring of subsequent broods. These findings suggest that the main effect of MeOH is to induce chromosomal malsegregation when present at the resumption of M-phase I after fertilization, probably due to perturbations in the nuclear membrane. Therefore, negative results with assays that evaluate DNA damage do not imply that the compound tested is not a potential hazard because other cellular components could be modified.
{"title":"Chromosome malsegregation induced by methanol in Drosophila melanogaster females","authors":"Ana María Palermo, Eliana Ruth Steinberg, Marta Dolores Mudry","doi":"10.1016/j.mrgentox.2025.503912","DOIUrl":"10.1016/j.mrgentox.2025.503912","url":null,"abstract":"<div><div>Methanol (MeOH) is a colorless, flammable, poisonous, alcohol that causes intoxication by ingesting, inhaling or by contact with formulations that include it. It is produced in large volumes and there is high level of human exposure, especially by the inhalation route. It has been reported as innocuous in various test systems; thus, the aim of this work was to search for <em>in vivo</em> genotoxic effects of MeOH in <em>Drosophila melanogaster</em>, studying its ability to induce nondisjunction (ND) in females. Treatments were acute (60 min) and via inhalation. It was toxic in 1-day old flies (<em>MI</em> = 63 % for 75 % MeOH) and in 5-days old flies (<em>MI</em> = 8.4 %, 40 % MeOH). Female fertility was severely affected during the first 24 h after treatment, later control values were recovered. MeOH induced a 16-fold increase of ND (%) in 1-day old females, and a 9-fold rise in 5-days old female’s offspring, but control values were recovered in the offspring of subsequent broods. These findings suggest that the main effect of MeOH is to induce chromosomal malsegregation when present at the resumption of M-phase I after fertilization, probably due to perturbations in the nuclear membrane. Therefore, negative results with assays that evaluate DNA damage do not imply that the compound tested is not a potential hazard because other cellular components could be modified.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"909 ","pages":"Article 503912"},"PeriodicalIF":2.5,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788055","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}
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