Pub Date : 2025-12-06DOI: 10.1016/j.mrgentox.2025.503905
Iqra Subhan , Tanishka Gupta , Kajal Gaur , Javeria Fatima , Smita Jyoti , Yasir Hasan Siddique
Drosophila melanogaster third-instar larvae were exposed to AlCl₃ in the diet for 24 h. Dose-dependent reductions in pupation and adult emergence were observed, Biochemical analyses revealed significantly elevated oxidative stress markers: increased lipid peroxidation and protein oxidation and depletion of reduced glutathione and antioxidant enzymes such as superoxide dismutase, catalase, and glutathione transferase. At higher concentrations, larvae also showed increased β-galactosidase activity and ONPG hydrolysis, suggesting lysosomal dysfunction and senescence-like responses.
{"title":"Toxicity and genotoxicity of AlCl3 in transgenic Drosophila melanogaster (hsp-70 lacZ) Bg9","authors":"Iqra Subhan , Tanishka Gupta , Kajal Gaur , Javeria Fatima , Smita Jyoti , Yasir Hasan Siddique","doi":"10.1016/j.mrgentox.2025.503905","DOIUrl":"10.1016/j.mrgentox.2025.503905","url":null,"abstract":"<div><div><em>Drosophila melanogaster</em> third-instar larvae were exposed to AlCl₃ in the diet for 24 h. Dose-dependent reductions in pupation and adult emergence were observed, Biochemical analyses revealed significantly elevated oxidative stress markers: increased lipid peroxidation and protein oxidation and depletion of reduced glutathione and antioxidant enzymes such as superoxide dismutase, catalase, and glutathione transferase. At higher concentrations, larvae also showed increased β-galactosidase activity and ONPG hydrolysis, suggesting lysosomal dysfunction and senescence-like responses.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"909 ","pages":"Article 503905"},"PeriodicalIF":2.5,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788053","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 : 2025-12-03DOI: 10.1016/j.mrgentox.2025.503904
Diene da Silva Schlickmann , Gabriela Cristina Uebel , Patrícia Molz , Nikolas Mateus Pereira de Souza , Renato Alberto Weber Colombelli , Aline Alves da Luz , Munithele Moraes Eisenhardt , Geovana Andrine Vogt , Caroline Brand , Eliane Aparecida de Castro , Pedro J. Benito , Alexandre Rieger , Silvia Isabel Rech Franke
This cross-sectional study evaluated dietary and lifestyle factors potentially contributing to DNA damage, cytokinetic defects, proliferative potential, and cell death among gym users in Brazil and Spain. We assessed demographic data, exercise habits, and nutrient estimated intake in 127 Brazilians and 101 Spaniards (≥18 years). DNA damage (micronuclei and/or nuclear buds), cytokinetic defects (binucleated cells), proliferative potential (normal cell frequency), and cell death (condensed chromatin, karyorrhexis, pyknotic, and karyolytic cells) were evaluated using the buccal micronucleus cytome assay (BMCyt). Multivariate analysis using partial least-squares discriminant analysis (PLS-DA) revealed significant discrimination between populations (AUC=0.976, sensitivity=90 %, specificity=95 %). Brazilians showed higher estimated carbohydrate consumption (220.9 vs 182.8 g/day, p = 0.001) and increased cell death markers, particularly karyorrhexis cells (p < 0.001; r = 0.94). Spaniards exhibited higher estimated intake of protein (121.1 vs 89.5 g/day), vitamins E and C, and manganese (all p < 0.001), with lower cellular damage frequencies. Results suggest a higher estimated intake of dietary antioxidants may provide protective effects against cytotoxic damage in different cultural contexts.
{"title":"Genotoxic and cytotoxic effects of dietary patterns and lifestyle factors: A cross-sectional comparison of Brazilian and Spanish gym users","authors":"Diene da Silva Schlickmann , Gabriela Cristina Uebel , Patrícia Molz , Nikolas Mateus Pereira de Souza , Renato Alberto Weber Colombelli , Aline Alves da Luz , Munithele Moraes Eisenhardt , Geovana Andrine Vogt , Caroline Brand , Eliane Aparecida de Castro , Pedro J. Benito , Alexandre Rieger , Silvia Isabel Rech Franke","doi":"10.1016/j.mrgentox.2025.503904","DOIUrl":"10.1016/j.mrgentox.2025.503904","url":null,"abstract":"<div><div>This cross-sectional study evaluated dietary and lifestyle factors potentially contributing to DNA damage, cytokinetic defects, proliferative potential, and cell death among gym users in Brazil and Spain. We assessed demographic data, exercise habits, and nutrient estimated intake in 127 Brazilians and 101 Spaniards (≥18 years). DNA damage (micronuclei and/or nuclear buds), cytokinetic defects (binucleated cells), proliferative potential (normal cell frequency), and cell death (condensed chromatin, karyorrhexis, pyknotic, and karyolytic cells) were evaluated using the buccal micronucleus cytome assay (BMCyt). Multivariate analysis using partial least-squares discriminant analysis (PLS-DA) revealed significant discrimination between populations (AUC=0.976, sensitivity=90 %, specificity=95 %). Brazilians showed higher estimated carbohydrate consumption (220.9 vs 182.8 g/day, p = 0.001) and increased cell death markers, particularly karyorrhexis cells (p < 0.001; r = 0.94). Spaniards exhibited higher estimated intake of protein (121.1 vs 89.5 g/day), vitamins E and C, and manganese (all p < 0.001), with lower cellular damage frequencies. Results suggest a higher estimated intake of dietary antioxidants may provide protective effects against cytotoxic damage in different cultural contexts.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"909 ","pages":"Article 503904"},"PeriodicalIF":2.5,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145683681","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 : 2025-11-01DOI: 10.1016/j.mrgentox.2025.503903
Keya Katare , Rohit Shetty , Arkasubhra Ghosh
Retinoblastoma (RB) is the most common pediatric ocular malignancy resulting from biallelic inactivation of the RB1 gene and can be fatal if not treated. With advances in chemotherapy and earlier diagnosis, the mortality rates in developed nations such as USA, Europe and Canada, have reduced to 3–5 %. Subsequently, the clinical focus has shifted to preserving visual acuity in these countries, whereas in developing nations, mortality rates still range from 40 % to 70 %. In India, about 70 % of the children presenting with RB in the clinic have already progressed to category D or E tumors. Since chemotherapy is still a mainstay of RB treatment, bystander toxicity remains an important concern. Although enucleation is necessary in 40–60 % of the RB cases, prior chemotherapy is still administered in most cases to debulk the tumors. As the majority of drugs used in chemotherapy employ DNA damaging agents, the review attempts to summarize the current knowledge regarding dysregulated DNA damage repair (DDR) genes in RB. Loss of the RB1 gene causes not only unrestricted cell cycle progression and cell division, driven by the E2F transcription factor family, but also leads to the accumulation of various other mutations and chromosomal aberrations, which may have a specific impact on the patients’ response to chemotherapy. Therefore, developing a more detailed perspective on the RB tumor DNA damage repair pathways is the focus of this review. Crystallizing the available information, we also propose the use of a few DDR inhibitors of the identified deregulated genes in retinoblastoma that are currently in clinical trials for other cancer types, as adjunct therapy to increase chemosensitivity of RB tumors and reduce chemotherapy-induced toxicity for better treatment outcomes.
{"title":"The potential implications of dysregulated DNA damage repair genes and their modulators as adjuvants for current chemotherapy regimens in Retinoblastoma tumors","authors":"Keya Katare , Rohit Shetty , Arkasubhra Ghosh","doi":"10.1016/j.mrgentox.2025.503903","DOIUrl":"10.1016/j.mrgentox.2025.503903","url":null,"abstract":"<div><div>Retinoblastoma (RB) is the most common pediatric ocular malignancy resulting from biallelic inactivation of the RB1 gene and can be fatal if not treated. With advances in chemotherapy and earlier diagnosis, the mortality rates in developed nations such as USA, Europe and Canada, have reduced to 3–5 %. Subsequently, the clinical focus has shifted to preserving visual acuity in these countries, whereas in developing nations, mortality rates still range from 40 % to 70 %. In India, about 70 % of the children presenting with RB in the clinic have already progressed to category D or E tumors. Since chemotherapy is still a mainstay of RB treatment, bystander toxicity remains an important concern. Although enucleation is necessary in 40–60 % of the RB cases, prior chemotherapy is still administered in most cases to debulk the tumors. As the majority of drugs used in chemotherapy employ DNA damaging agents, the review attempts to summarize the current knowledge regarding dysregulated DNA damage repair (DDR) genes in RB. Loss of the RB1 gene causes not only unrestricted cell cycle progression and cell division, driven by the E2F transcription factor family, but also leads to the accumulation of various other mutations and chromosomal aberrations, which may have a specific impact on the patients’ response to chemotherapy. Therefore, developing a more detailed perspective on the RB tumor DNA damage repair pathways is the focus of this review. Crystallizing the available information, we also propose the use of a few DDR inhibitors of the identified deregulated genes in retinoblastoma that are currently in clinical trials for other cancer types, as adjunct therapy to increase chemosensitivity of RB tumors and reduce chemotherapy-induced toxicity for better treatment outcomes.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"908 ","pages":"Article 503903"},"PeriodicalIF":2.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681130","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 : 2025-11-01DOI: 10.1016/j.mrgentox.2025.503901
Samit B. Kadam , MR Mayookh , N. Bhumika , Satendra Singh , Aditya Hazare , Rohini Karnat
We review the results of the ‘Enhanced’ Ames Test (EAT) for assessment of the mutagenicity of N-nitrosamines, integrating the data from six key studies. High (>98 %) purities of the nitrosamines were confirmed by LC-MS and glutathione co-incubation to avoid false-positive results. The most sensitive strains were Salmonella typhimurium TA1535 and Escherichia coli WP2 uvrA (pKM101), which detect primarily GC→AT transitions, typically induced by O6-alkylguanine DNA adducts. Strain TA100 gave variable responses and strains TA98 and TA1537 gave negative results. Bioactivation by hamster liver S9 (particularly at the 30 % v/v level), rich in cytochrome P450 (CYP) forms 2E1 and 2C19, was more effective than rat liver S9. N-Methyl-2-pyrrolidone and ethyl acetate inhibited metabolic activation but DMSO (up to 1.6 % v/v) and water did not. These findings support the use of a tiered EAT strategy with TA1535, WP2 uvrA, hamster S9, and validated solvents, in agreement with published guidelines, for the robust risk assessment of nitrosamine mutagenicity.
{"title":"Mutagenicity of nitrosamines in enhanced Ames tests: A review of strain, metabolism, and solvent effects","authors":"Samit B. Kadam , MR Mayookh , N. Bhumika , Satendra Singh , Aditya Hazare , Rohini Karnat","doi":"10.1016/j.mrgentox.2025.503901","DOIUrl":"10.1016/j.mrgentox.2025.503901","url":null,"abstract":"<div><div>We review the results of the ‘Enhanced’ Ames Test (EAT) for assessment of the mutagenicity of N-nitrosamines, integrating the data from six key studies. High (>98 %) purities of the nitrosamines were confirmed by LC-MS and glutathione co-incubation to avoid false-positive results. The most sensitive strains were <em>Salmonella typhimurium</em> TA1535 and <em>Escherichia coli</em> WP2 <em>uvr</em>A (pKM101), which detect primarily GC→AT transitions, typically induced by O<sup>6</sup>-alkylguanine DNA adducts. Strain TA100 gave variable responses and strains TA98 and TA1537 gave negative results. Bioactivation by hamster liver S9 (particularly at the 30 % v/v level), rich in cytochrome P450 (CYP) forms 2E1 and 2C19, was more effective than rat liver S9. <em>N</em>-Methyl-2-pyrrolidone and ethyl acetate inhibited metabolic activation but DMSO (up to 1.6 % v/v) and water did not. These findings support the use of a tiered EAT strategy with TA1535, WP2 <em>uvrA</em>, hamster S9, and validated solvents, in agreement with published guidelines, for the robust risk assessment of nitrosamine mutagenicity.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"908 ","pages":"Article 503901"},"PeriodicalIF":2.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145428595","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 : 2025-11-01DOI: 10.1016/j.mrgentox.2025.503902
Makoto Hayashi , Takashi Omori
The appropriate strategy for a genotoxicity assessment depends on the purpose of the study. If the purpose is research-oriented (for example, to understand mechanisms of gene-mutation events or chromosomal aberrations), the tests should meet the researcher’s scientific goals. However, to make regulatory decisions with confidence, the genotoxicity strategy must cover all necessary endpoints. Thus, it is crucial to standardize the relevant test methods and to certify reproducible experimental processes. A battery system, which is often used for genotoxicity evaluation, consists of several tests that complementarily detect different endpoints. Numerous genotoxicity tests are available, employing various organisms and methodologies, and it is therefore crucial to select the appropriate tests for the battery system. Sensitivity and specificity are essential considerations. These are inversely correlated, and we cannot maximize them simultaneously; our interest tends to lie more with sensitivity than specificity; that is, we want to avoid false negatives. We also discuss the issues arising in parallel from a statistical perspective, namely type I and II errors. Genotoxicity is a crucial endpoint for decision-making in human safety assessment, and the issues mentioned above must be thoroughly understood and considered.
{"title":"Selection of tests for genotoxicity assessment: Sensitivity and specificity considerations","authors":"Makoto Hayashi , Takashi Omori","doi":"10.1016/j.mrgentox.2025.503902","DOIUrl":"10.1016/j.mrgentox.2025.503902","url":null,"abstract":"<div><div>The appropriate strategy for a genotoxicity assessment depends on the purpose of the study. If the purpose is research-oriented (for example, to understand mechanisms of gene-mutation events or chromosomal aberrations), the tests should meet the researcher’s scientific goals. However, to make regulatory decisions with confidence, the genotoxicity strategy must cover all necessary endpoints. Thus, it is crucial to standardize the relevant test methods and to certify reproducible experimental processes. A battery system, which is often used for genotoxicity evaluation, consists of several tests that complementarily detect different endpoints. Numerous genotoxicity tests are available, employing various organisms and methodologies, and it is therefore crucial to select the appropriate tests for the battery system. Sensitivity and specificity are essential considerations. These are inversely correlated, and we cannot maximize them simultaneously; our interest tends to lie more with sensitivity than specificity; that is, we want to avoid false negatives. We also discuss the issues arising in parallel from a statistical perspective, namely type I and II errors. Genotoxicity is a crucial endpoint for decision-making in human safety assessment, and the issues mentioned above must be thoroughly understood and considered.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"908 ","pages":"Article 503902"},"PeriodicalIF":2.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733205","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 : 2025-10-01DOI: 10.1016/j.mrgentox.2025.503900
Naveed Honarvar , Astrid Zander , Miyuki Shigano , Eva Dony , Brandy Riffle , Markus Frericks , Tobias Seiser , Robert Landsiedel
Protoporphyrinogen-oxidase inhibitors (PPOi) are a class of herbicides that target chlorophyll synthesis in plants. Similarly, they affect heme synthesis in mammals, resulting in anemia. A new PPOi development candidate showed micronucleus formation in the bone marrow of rodents in vivo. Increased erythropoiesis has previously been described to increase micronucleus formation in the bone marrow. Hence, the micronuclei (MN) observed after administration of the new PPOi candidate may be caused by increased erythropoiesis rather than direct genotoxicity. To investigate this, the mutagenicity in vitro was examined and found to be clearly negative. In addition, micronucleus formation in vivo was investigated after administration of the new PPOi in doses that caused anemia. Both, erythropoietic and non-erythropoietic tissues, bone marrow and liver, were investigated. Moreover, genotoxicity was investigated by the Comet-assay in erythroid and non-erythroid cells of the bone marrow. The new PPOi did not show mutagenic effects in vitro. The new PPOi induced an increase in the micronucleus counts in the bone marrow of rats, whereas the hepatocytes were not affected. In another study in mice, micronucleus formation was observed in the new PPOi-exposed bone marrow. In parallel, bone marrow cells of the same animals were separated into subpopulations isolating erythroid (selected via their Ter119 surface marker) and non-erythroid (selected by their CD45 surface marker) cells, which were then assessed in a comet assay. Results showed a dose dependent increase in micronucleus frequencies while, increases in % DNA tail intensities in the comet assay were only observed in the erythroid Ter119+ subpopulation, but not in non-erythroid bone marrow cells. This provides evidence that the new PPOi induces MN only upon induction of anemia, and that the DNA-damage is only occurring in erythroid cells. The increased micronucleus-formation of the new PPOi in vivo is hence most likely caused by erythropoiesis and not by direct genotoxic actions.
{"title":"Evidence of erythropoiesis rather than direct genotoxicity causing micronucleus induction by a new protoporphyrinogen-oxidase inhibitor","authors":"Naveed Honarvar , Astrid Zander , Miyuki Shigano , Eva Dony , Brandy Riffle , Markus Frericks , Tobias Seiser , Robert Landsiedel","doi":"10.1016/j.mrgentox.2025.503900","DOIUrl":"10.1016/j.mrgentox.2025.503900","url":null,"abstract":"<div><div>Protoporphyrinogen-oxidase inhibitors (PPOi) are a class of herbicides that target chlorophyll synthesis in plants. Similarly, they affect heme synthesis in mammals, resulting in anemia. A new PPOi development candidate showed micronucleus formation in the bone marrow of rodents <em>in vivo</em>. Increased erythropoiesis has previously been described to increase micronucleus formation in the bone marrow. Hence, the micronuclei (MN) observed after administration of the new PPOi candidate may be caused by increased erythropoiesis rather than direct genotoxicity. To investigate this, the mutagenicity <em>in vitro</em> was examined and found to be clearly negative. In addition, micronucleus formation <em>in vivo</em> was investigated after administration of the new PPOi in doses that caused anemia. Both, erythropoietic and non-erythropoietic tissues, bone marrow and liver, were investigated. Moreover, genotoxicity was investigated by the Comet-assay in erythroid and non-erythroid cells of the bone marrow. The new PPOi did not show mutagenic effects <em>in vitro</em>. The new PPOi induced an increase in the micronucleus counts in the bone marrow of rats, whereas the hepatocytes were not affected. In another study in mice, micronucleus formation was observed in the new PPOi-exposed bone marrow. In parallel, bone marrow cells of the same animals were separated into subpopulations isolating erythroid (selected <em>via</em> their Ter119 surface marker) and non-erythroid (selected by their CD45 surface marker) cells, which were then assessed in a comet assay. Results showed a dose dependent increase in micronucleus frequencies while, increases in % DNA tail intensities in the comet assay were only observed in the erythroid Ter119<sup>+</sup> subpopulation, but not in non-erythroid bone marrow cells. This provides evidence that the new PPOi induces MN only upon induction of anemia, and that the DNA-damage is only occurring in erythroid cells. The increased micronucleus-formation of the new PPOi <em>in vivo</em> is hence most likely caused by erythropoiesis and not by direct genotoxic actions.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"907 ","pages":"Article 503900"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145265986","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 : 2025-10-01Epub Date: 2025-08-07DOI: 10.1016/j.mrgentox.2025.503882
Emilio Rojas, Víctor Calderón-Salinas, Pablo Hérnandez-Franco, Brenda Loaiza, María Maldonado-Vega, Elia Martínez-Baeza, Patricia Mussali-Galante, Paulina Ramos-Espinosa, Martín Silva-Aguilar, Efraín Tovar-Sánchez, Nahum Zepeta-Flores, Mahara Valverde
Occupational exposure is a problem that needs to be understood to implement action that prevent diseases. In this cross-sectional study, we monitored the total (116) workers at a battery recycling plant. The objective was to understand if the oxidative biomarkers of lead exposure are of relevance to the functionality of DNA-repair mechanisms. We determined in all of them the Blood Lead Levels (BLL), δ-ALAD activity, lipid peroxidation, DNA damage (alkaline comet assay) and the ability to repair damage induced by ionizing radiation. Our results indicate that Pb-exposed workers exceed the permissible exposure limits and present high values of all variables determined. It was found that BLL and genotoxicity determined in workers show correlation with years worked, δ-ALAD activity and DNA repair capacity, while lipid peroxidation only correlated with BLL. The main result of the study was the detection of elevated oxidative damage in workers exposed to Pb, with no correlation established with the functionality of DNA repair mechanisms (they only repair 50 % of the induced damage). This finding suggests that the oxidative damage generated by Pb partially compromises the genetic stability of these workers, who have worked an average of 5 years at this recycling plant despite exceeding permissible exposure levels. This highlights the need for future studies to determine the induction of systemic homeostasis mechanisms that remain functional in workers, despite their exposure levels.
{"title":"Workers exposed to lead at a battery recycling plant in Mexico: Blood lead levels; DNA damage and repair in blood cells (comet assay).","authors":"Emilio Rojas, Víctor Calderón-Salinas, Pablo Hérnandez-Franco, Brenda Loaiza, María Maldonado-Vega, Elia Martínez-Baeza, Patricia Mussali-Galante, Paulina Ramos-Espinosa, Martín Silva-Aguilar, Efraín Tovar-Sánchez, Nahum Zepeta-Flores, Mahara Valverde","doi":"10.1016/j.mrgentox.2025.503882","DOIUrl":"https://doi.org/10.1016/j.mrgentox.2025.503882","url":null,"abstract":"<p><p>Occupational exposure is a problem that needs to be understood to implement action that prevent diseases. In this cross-sectional study, we monitored the total (116) workers at a battery recycling plant. The objective was to understand if the oxidative biomarkers of lead exposure are of relevance to the functionality of DNA-repair mechanisms. We determined in all of them the Blood Lead Levels (BLL), δ-ALAD activity, lipid peroxidation, DNA damage (alkaline comet assay) and the ability to repair damage induced by ionizing radiation. Our results indicate that Pb-exposed workers exceed the permissible exposure limits and present high values of all variables determined. It was found that BLL and genotoxicity determined in workers show correlation with years worked, δ-ALAD activity and DNA repair capacity, while lipid peroxidation only correlated with BLL. The main result of the study was the detection of elevated oxidative damage in workers exposed to Pb, with no correlation established with the functionality of DNA repair mechanisms (they only repair 50 % of the induced damage). This finding suggests that the oxidative damage generated by Pb partially compromises the genetic stability of these workers, who have worked an average of 5 years at this recycling plant despite exceeding permissible exposure levels. This highlights the need for future studies to determine the induction of systemic homeostasis mechanisms that remain functional in workers, despite their exposure levels.</p>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"907 ","pages":"503882"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145409516","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 : 2025-09-26DOI: 10.1016/j.mrgentox.2025.503899
Emanuele D'Anza , Ilaria Cascone , Flavio Luongo , Sara Albarella , Francesca Ciotola , Luigi Liotta , Vincenzo Peretti
This study investigates chromosomal damage in donkeys to assess the impact of long-term exposure to different concentrations of environmental genotoxic agents, which pose health risks to animals and humans by promoting DNA breaks. The genotoxic damage was assessed through aneuploidy, chromosomal aberrations (CAs), and sister chromatid exchanges (SCEs) tests in donkeys, crossbred Ragusano and Grigio Siciliano breeds, from three areas in the Sicily region (Italy) with different levels of air pollution. Donkeys from areas with higher concentrations of fine particulate matter and nitrogen dioxide showed significantly elevated levels of aneuploidy and chromosomal abnormalities compared to those from less polluted areas. These findings provide the first evidence in donkeys of the combined effects of long-term exposure to airborne pollutants on genomic stability. This study reinforces the potential use of donkeys as effective biomonitoring organisms for evaluating environmental health risks and genotoxic damage under different pollution conditions.
{"title":"Increased genotoxic damage in Sicilian donkeys reared in different conditions of air quality","authors":"Emanuele D'Anza , Ilaria Cascone , Flavio Luongo , Sara Albarella , Francesca Ciotola , Luigi Liotta , Vincenzo Peretti","doi":"10.1016/j.mrgentox.2025.503899","DOIUrl":"10.1016/j.mrgentox.2025.503899","url":null,"abstract":"<div><div>This study investigates chromosomal damage in donkeys to assess the impact of long-term exposure to different concentrations of environmental genotoxic agents, which pose health risks to animals and humans by promoting DNA breaks. The genotoxic damage was assessed through aneuploidy, chromosomal aberrations (CAs), and sister chromatid exchanges (SCEs) tests in donkeys, crossbred Ragusano and Grigio Siciliano breeds, from three areas in the Sicily region (Italy) with different levels of air pollution. Donkeys from areas with higher concentrations of fine particulate matter and nitrogen dioxide showed significantly elevated levels of aneuploidy and chromosomal abnormalities compared to those from less polluted areas. These findings provide the first evidence in donkeys of the combined effects of long-term exposure to airborne pollutants on genomic stability. This study reinforces the potential use of donkeys as effective biomonitoring organisms for evaluating environmental health risks and genotoxic damage under different pollution conditions.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"907 ","pages":"Article 503899"},"PeriodicalIF":2.5,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154356","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 : 2025-09-19DOI: 10.1016/j.mrgentox.2025.503898
Gulsah Yildiz Deniz
The Chernobyl nuclear accident of April 1986 remains the most severe nuclear disaster in human history, with long-lasting consequences for ecosystems exposed to chronic ionizing radiation. In the decades since the event, the Chernobyl Exclusion Zone has become an unintended but invaluable natural laboratory for investigating the genetic and ecological effects of persistent radiation exposure. This review synthesizes current knowledge on both immediate and long-term biological consequences observed in plants and animals inhabiting contaminated areas. Initial impacts included acute mortality, reproductive failure, and ecosystem collapse, most notably exemplified by the “Red Forest.” Over subsequent years, studies revealed elevated mutation rates, chromosomal aberrations, genomic instability, and heritable genetic damage across diverse taxa. At the same time, evidence of adaptive responses has emerged, including increased antioxidant defenses, epigenetic modifications, and phenotypic changes such as melanism in amphibians. Flora and fauna within the exclusion zone illustrate the dual narrative of vulnerability to mutagenic stress and resilience through evolutionary adaptation. Comparisons with the Fukushima accident demonstrate convergent biological responses across ecosystems while highlighting the importance of context, such as terrestrial versus marine contamination and remediation strategies. Future research must integrate advanced genomic and epigenomic tools, accurate dosimetry, and long-term monitoring to clarify thresholds for harmful versus adaptive outcomes. Chernobyl thus continues to provide critical insights into radiation biology, ecological recovery, and evolutionary toxicology under conditions of chronic environmental stress.
{"title":"Chernobyl as a natural laboratory: Genetic instability, adaptation, and ecological recovery in flora and fauna under chronic radiation","authors":"Gulsah Yildiz Deniz","doi":"10.1016/j.mrgentox.2025.503898","DOIUrl":"10.1016/j.mrgentox.2025.503898","url":null,"abstract":"<div><div>The Chernobyl nuclear accident of April 1986 remains the most severe nuclear disaster in human history, with long-lasting consequences for ecosystems exposed to chronic ionizing radiation. In the decades since the event, the Chernobyl Exclusion Zone has become an unintended but invaluable natural laboratory for investigating the genetic and ecological effects of persistent radiation exposure. This review synthesizes current knowledge on both immediate and long-term biological consequences observed in plants and animals inhabiting contaminated areas. Initial impacts included acute mortality, reproductive failure, and ecosystem collapse, most notably exemplified by the “Red Forest.” Over subsequent years, studies revealed elevated mutation rates, chromosomal aberrations, genomic instability, and heritable genetic damage across diverse taxa. At the same time, evidence of adaptive responses has emerged, including increased antioxidant defenses, epigenetic modifications, and phenotypic changes such as melanism in amphibians. Flora and fauna within the exclusion zone illustrate the dual narrative of vulnerability to mutagenic stress and resilience through evolutionary adaptation. Comparisons with the Fukushima accident demonstrate convergent biological responses across ecosystems while highlighting the importance of context, such as terrestrial versus marine contamination and remediation strategies. Future research must integrate advanced genomic and epigenomic tools, accurate dosimetry, and long-term monitoring to clarify thresholds for harmful versus adaptive outcomes. Chernobyl thus continues to provide critical insights into radiation biology, ecological recovery, and evolutionary toxicology under conditions of chronic environmental stress.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"907 ","pages":"Article 503898"},"PeriodicalIF":2.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145105379","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 : 2025-09-18DOI: 10.1016/j.mrgentox.2025.503897
Divya K. Mohan , Nandhini K. , Aishwarya S. , Senthil Kumar M. , Swetha K. , Akshaya J. , Sudha Pattan , Venkata Sai P.M. , Venkateswarlu Raavi , Venkatachalam Perumal
Computed tomography (CT) is a widely used diagnostic imaging modality that contributes significantly to human healthcare. Despite the advantage, its extensive use increased concerns due to receiving radiation doses to pediatric patient's over adults during CT imaging. We evaluated the biological effects (Gamma-H2AX (γ-H2AX) foci and micronucleus (MN) formation) of low-dose X-radiation on the peripheral blood lymphocytes of pediatric (n = 45) and adult (n = 38) participants before and after CT imaging. Participant-specific organ doses were calculated using VirtualDose™CT software, weighted to the corresponding organ's blood volume, summed to derive the blood dose, and then related to induced DNA damage. A significant (p < 0.001) increase in γ-H2AX foci and MN frequencies was observed in both pediatric and adult groups after CT imaging. While the mean effective dose (ED) in pediatric and adult (16.21 ± 11.33 mSv and 31.30 ± 16.25 mSv) participants were significantly different (p < 0.001), the mean blood doses did not differ (9.83 ± 6.34 mGy and 12.82 ± 5.96 mGy) (p > 0.05), respectively. A weak correlation was observed between the induced DNA damage to that of ED and blood dose. The results suggest that damage to blood lymphocytes after CT imaging was observed by an increased γ-H2AX foci result of DNA double-strand breaks. The increase in MN frequency suggests activation of DNA repair, thereby contributing to minimal damage, although they are unstable. Therefore, it is necessary to follow up on the pediatric participants to look for stable aberrations to better relate DNA damage to exposure and long-term health effects, if any.
{"title":"Frequency of γ-H2AX foci, micronucleus formation, and radiation dose to the blood lymphocytes in pediatric and adult participants underwent computed tomography imaging","authors":"Divya K. Mohan , Nandhini K. , Aishwarya S. , Senthil Kumar M. , Swetha K. , Akshaya J. , Sudha Pattan , Venkata Sai P.M. , Venkateswarlu Raavi , Venkatachalam Perumal","doi":"10.1016/j.mrgentox.2025.503897","DOIUrl":"10.1016/j.mrgentox.2025.503897","url":null,"abstract":"<div><div>Computed tomography (CT) is a widely used diagnostic imaging modality that contributes significantly to human healthcare. Despite the advantage, its extensive use increased concerns due to receiving radiation doses to pediatric patient's over adults during CT imaging. We evaluated the biological effects (Gamma-H2AX (γ-H2AX) foci and micronucleus (MN) formation) of low-dose X-radiation on the peripheral blood lymphocytes of pediatric (n = 45) and adult (n = 38) participants before and after CT imaging. Participant-specific organ doses were calculated using VirtualDose™CT software, weighted to the corresponding organ's blood volume, summed to derive the blood dose, and then related to induced DNA damage. A significant (p < 0.001) increase in γ-H2AX foci and MN frequencies was observed in both pediatric and adult groups after CT imaging. While the mean effective dose (ED) in pediatric and adult (16.21 ± 11.33 mSv and 31.30 ± 16.25 mSv) participants were significantly different (p < 0.001), the mean blood doses did not differ (9.83 ± 6.34 mGy and 12.82 ± 5.96 mGy) (p > 0.05), respectively. A weak correlation was observed between the induced DNA damage to that of ED and blood dose. The results suggest that damage to blood lymphocytes after CT imaging was observed by an increased γ-H2AX foci result of DNA double-strand breaks. The increase in MN frequency suggests activation of DNA repair, thereby contributing to minimal damage, although they are unstable. Therefore, it is necessary to follow up on the pediatric participants to look for stable aberrations to better relate DNA damage to exposure and long-term health effects, if any.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"907 ","pages":"Article 503897"},"PeriodicalIF":2.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154355","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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