Pub Date : 2025-10-01Epub 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":"2025-10-01","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 : 2025-10-01Epub Date: 2025-10-02DOI: 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: 2025-09-19DOI: 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":"2025-10-01","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 : 2025-10-01Epub Date: 2025-09-09DOI: 10.1016/j.mrgentox.2025.503886
Liang Wang , Li Cao , Xiaoya Wang , Yufei Liu , Weiwei Zhang , Yurui Gou , Jun He , Jiao Huo , Xiaomeng Li , Jinyao Chen
As a commonly used material that contacts food, polyethylene glycol terephthalate (PET) may interact with food, and since certain components can migrate, this has become a food safety concern. This study aims to investigate the genotoxicity of PET acetic acid migration solution and its toxic mode of action using an in vivo multi-endpoint genotoxicity evaluation system and quantitative liver proteomics analysis. Forty-eight male Sprague–Dawley rats were randomly divided into eight groups: the PET acetic acid migration solution group, the acetic acid group, the phosphate-buffered saline (PBS) control group, the N-ethyl-N-nitrosourea (ENU) positive control group, and their corresponding satellite groups. PBS and ENU were administered by gavage, while the PET acetic acid migration solution and acetic acid were administered orally in the drinking water. The exposure duration was 35 days, followed by a recovery period of 15 days. The PET acetic acid migration solution can cause heart, liver, and kidney injury in rats. On the 15th day, mutations were seen in the Pig-a gene test. On the 35th day, DNA damage was observed in peripheral blood and liver cells. Gene ontology (GO) analysis of the liver proteomics revealed enrichment in DNA metabolism and binding processes, while Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis highlighted the DNA replication pathway. Immunohistochemical analysis demonstrated a significant increase in 8-hydroxydeoxyguanosine (8-OHdG) and a decrease in single-stranded-binding (SSB) protein in the PET acetic acid migration solution group. In summary, the PET acetic acid migration solution has the potential to induce DNA damage, possibly by inhibiting DNA replication and DNA repair pathways. However, the likelihood of genetic toxicity is low.
{"title":"Genotoxicity mode of action exploration of polyethylene glycol terephthalate (PET) acetic acid migration solution under repeated-dose exposure in rats","authors":"Liang Wang , Li Cao , Xiaoya Wang , Yufei Liu , Weiwei Zhang , Yurui Gou , Jun He , Jiao Huo , Xiaomeng Li , Jinyao Chen","doi":"10.1016/j.mrgentox.2025.503886","DOIUrl":"10.1016/j.mrgentox.2025.503886","url":null,"abstract":"<div><div>As a commonly used material that contacts food, polyethylene glycol terephthalate (PET) may interact with food, and since certain components can migrate, this has become a food safety concern. This study aims to investigate the genotoxicity of PET acetic acid migration solution and its toxic mode of action using an <em>in vivo</em> multi-endpoint genotoxicity evaluation system and quantitative liver proteomics analysis. Forty-eight male Sprague–Dawley rats were randomly divided into eight groups: the PET acetic acid migration solution group, the acetic acid group, the phosphate-buffered saline (PBS) control group, the N-ethyl-N-nitrosourea (ENU) positive control group, and their corresponding satellite groups. PBS and ENU were administered by gavage, while the PET acetic acid migration solution and acetic acid were administered orally in the drinking water. The exposure duration was 35 days, followed by a recovery period of 15 days. The PET acetic acid migration solution can cause heart, liver, and kidney injury in rats. On the 15th day, mutations were seen in the <em>Pig-a</em> gene test. On the 35th day, DNA damage was observed in peripheral blood and liver cells. Gene ontology (GO) analysis of the liver proteomics revealed enrichment in DNA metabolism and binding processes, while Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis highlighted the DNA replication pathway. Immunohistochemical analysis demonstrated a significant increase in 8-hydroxydeoxyguanosine (8-OHdG) and a decrease in single-stranded-binding (SSB) protein in the PET acetic acid migration solution group. In summary, the PET acetic acid migration solution has the potential to induce DNA damage, possibly by inhibiting DNA replication and DNA repair pathways. However, the likelihood of genetic toxicity is low.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"907 ","pages":"Article 503886"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043960","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}
Asthma is a chronic, non-communicable respiratory disorder affecting approximately 262 million people worldwide, with India projected to become one of the leading countries in prevalence. Asthma is well-established as a condition of chronic inflammation of the airways and related to systemic oxidative stress, but relatively not much is known about the genomic instability associated with asthma. On the other hand, obesity is found in 650 million people worldwide and 113 million people in India. Studies reported links between asthma and obesity, which include adipose tissue dysfunction and inefficient blood monocyte efferocytosis. Obesity enhances reactive oxygen species (ROS) production and inflammation, leading to DNA lesions. Thus, the aim of this study was to assess the DNA damage and frequencies of micronuclei (MNi), nucleoplasmic bridges (NPB), and nuclear buds (NBUD) in the lymphocytes of asthma patients and obese individuals. This study evaluates the DNA damage and nuclear anomalies in (n = 435) subjects (asthma patients n = 100, asthmatic obese patients n = 131, obese n = 100 and controls n = 104). An alkaline comet assay was used to assess DNA damage and nuclear anomalies were assessed by cytokinesis block micronucleus cytome (CBMN-Cyt) assay. All subjects were recruited between the age of 20 and 60 years. The total DNA damage, MNi, and frequency of total nuclear anomalies were found to be significantly higher in asthma male and female patients, asthmatic obese male and female patients, and obese males and females in comparison to control males and females (p < 0.05). The total comet score showed a positive correlation with the frequency of total nuclear anomalies in asthma male and female patients and obese males, respectively. Overall the findings demonstrate that inflammation and oxidative stress in asthma and obesity lead to DNA damage and genomic instability.
{"title":"DNA damage and nuclear anomalies in peripheral blood lymphocytes from asthma patients and obese individuals","authors":"Aswathi Pootheri , Medha Nagaraj , Nethra Raghuraman , Sohini Dey , Swathi R , Sombodhi Bhattacharya , Yeshi Yangchen , S. Santoshi Iyer , Mohnish Ram G , Narmada Ashok , Wilner Martinez Lopez , Radha Saraswathy","doi":"10.1016/j.mrgentox.2025.503889","DOIUrl":"10.1016/j.mrgentox.2025.503889","url":null,"abstract":"<div><div>Asthma is a chronic, non-communicable respiratory disorder affecting approximately 262 million people worldwide, with India projected to become one of the leading countries in prevalence. Asthma is well-established as a condition of chronic inflammation of the airways and related to systemic oxidative stress, but relatively not much is known about the genomic instability associated with asthma. On the other hand, obesity is found in 650 million people worldwide and 113 million people in India. Studies reported links between asthma and obesity, which include adipose tissue dysfunction and inefficient blood monocyte efferocytosis. Obesity enhances reactive oxygen species (ROS) production and inflammation, leading to DNA lesions. Thus, the aim of this study was to assess the DNA damage and frequencies of micronuclei (MNi), nucleoplasmic bridges (NPB), and nuclear buds (NBUD) in the lymphocytes of asthma patients and obese individuals. This study evaluates the DNA damage and nuclear anomalies in (n = 435) subjects (asthma patients n = 100, asthmatic obese patients n = 131, obese n = 100 and controls n = 104). An alkaline comet assay was used to assess DNA damage and nuclear anomalies were assessed by cytokinesis block micronucleus cytome (CBMN-Cyt) assay. All subjects were recruited between the age of 20 and 60 years. The total DNA damage, MNi, and frequency of total nuclear anomalies were found to be significantly higher in asthma male and female patients, asthmatic obese male and female patients, and obese males and females in comparison to control males and females (p < 0.05). The total comet score showed a positive correlation with the frequency of total nuclear anomalies in asthma male and female patients and obese males, respectively. Overall the findings demonstrate that inflammation and oxidative stress in asthma and obesity lead to DNA damage and genomic instability.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"907 ","pages":"Article 503889"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145099560","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: 2025-09-10DOI: 10.1016/j.mrgentox.2025.503888
Milda Babonaitė, Veronika Dedonytė, Emilija Striogaitė, Juozas R. Lazutka
Cobalt (II, III) oxide nanoparticles (Co3O4-NPs) have potential applications in different technological and medical fields, including drug delivery and as novel anticancer treatments. However, widespread application could lead to a high-level direct human exposure, raising concerns about their genotoxic potential. This study aimed to evaluate the cytotoxicity and genotoxicity of Co3O4-NPs in human peripheral blood mononuclear cells (PBMCs) in vitro. Two sizes of Co3O4-NPs (10–30 nm and < 50 nm) were tested to understand any size-dependent differences in genotoxicity. The study measured NP uptake, reactive oxygen species (ROS) generation, cell viability, DNA strand breaks, micronuclei formation, and sister chromatid exchange to assess the cyto-genotoxic potential of Co3O4-NPs. Flow cytometric analysis revealed that Co3O4-NPs with a primary size of < 50 nm were more efficiently internalized by human PBMCs and induced higher ROS levels than 10–30 nm particles. Both nanoparticles’ sizes induced significant primary DNA damage at non-cytotoxic concentrations, often in a dose-dependent manner. Cytogenetic analysis demonstrated that Co3O4-NPs exert genotoxic effects, with < 50 nm NPs inducing more significant DNA damage and reduced cell viability than smaller nanoparticles. Additionally, interindividual differences in response to exposure to Co3O4–NPs were observed. The study findings suggest that Co3O4-NPs possess genotoxic potential in human PBMCs in vitro, raising safety concerns about their use. This highlights the need for comprehensive genotoxicity assessments of Co3O4-NPs in different cell types.
{"title":"Cellular uptake, induction of reactive oxygen species, and genotoxicity of differently sized cobalt oxide nanoparticles in human peripheral blood mononuclear cells in vitro","authors":"Milda Babonaitė, Veronika Dedonytė, Emilija Striogaitė, Juozas R. Lazutka","doi":"10.1016/j.mrgentox.2025.503888","DOIUrl":"10.1016/j.mrgentox.2025.503888","url":null,"abstract":"<div><div>Cobalt (II, III) oxide nanoparticles (Co<sub>3</sub>O<sub>4</sub>-NPs) have potential applications in different technological and medical fields, including drug delivery and as novel anticancer treatments. However, widespread application could lead to a high-level direct human exposure, raising concerns about their genotoxic potential. This study aimed to evaluate the cytotoxicity and genotoxicity of Co<sub>3</sub>O<sub>4</sub>-NPs in human peripheral blood mononuclear cells (PBMCs) <em>in vitro.</em> Two sizes of Co<sub>3</sub>O<sub>4</sub>-NPs (10–30 nm and < 50 nm) were tested to understand any size-dependent differences in genotoxicity. The study measured NP uptake, reactive oxygen species (ROS) generation, cell viability, DNA strand breaks, micronuclei formation, and sister chromatid exchange to assess the cyto-genotoxic potential of Co<sub>3</sub>O<sub>4</sub>-NPs. Flow cytometric analysis revealed that Co<sub>3</sub>O<sub>4</sub>-NPs with a primary size of < 50 nm were more efficiently internalized by human PBMCs and induced higher ROS levels than 10–30 nm particles. Both nanoparticles’ sizes induced significant primary DNA damage at non-cytotoxic concentrations, often in a dose-dependent manner. Cytogenetic analysis demonstrated that Co<sub>3</sub>O<sub>4</sub>-NPs exert genotoxic effects, with < 50 nm NPs inducing more significant DNA damage and reduced cell viability than smaller nanoparticles. Additionally, interindividual differences in response to exposure to Co<sub>3</sub>O<sub>4</sub>–NPs were observed. The study findings suggest that Co<sub>3</sub>O<sub>4</sub>-NPs possess genotoxic potential in human PBMCs <em>in vitro</em>, raising safety concerns about their use. This highlights the need for comprehensive genotoxicity assessments of Co<sub>3</sub>O<sub>4</sub>-NPs in different cell types.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"907 ","pages":"Article 503888"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043959","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 : 2025-08-01Epub Date: 2025-07-25DOI: 10.1016/j.mrgentox.2025.503878
Cynthia Recoules , Chloé Huertas , Julien Vignard, Marc Audebert
Chemical risk assessment relies on in vitro genotoxicity tests. Histone modifications (γH2AX and pH3) have emerged as valuable biomarkers for genotoxicity detection. In this study, we compared three parameters (global intensity, nuclear intensity, and foci number) for the γH2AX biomarker and two parameters (global intensity and % cell in mitosis) for the pH3 biomarker. These analyzes were performed in three cell lines: human osteosarcoma U2OS cells, human hepatocellular carcinoma HepG2 cells and rat intestinal epithelial IEC-6 cells. Cells were exposed for 24 h to four well-characterized hazardous substances: nocodazole (aneugen), etoposide (topoisomerase inhibitor), benzo[a]pyrene (DNA adducts inducer), and tunicamycin (apoptosis inducer). The Benchmark Concentration (BMC) approach indicated that the sensitivity of the technics varied depending on both the chemical compounds and the tested cell line. The γH2AX foci analysis provided the higher sensitivity for clastogenic compounds. For the aneugenic compound, the global intensity and the proportion of mitotic cells showed similar sensitivity. Following tunicamycin treatment, we only detected increase in γH2AX nuclear intensity in U2OS cell model, indicating that apoptosis does not interfere with γH2AX global intensity or foci number, thereby minimizing the risk of false positive results. Finally, we observed that compared to the other methods, global intensity permitted to monitor weaker fold inductions of the biomarkers. By comparing the different quantification methods of histone modifications used as genotoxicity biomarkers, this study highlights the most suitable parameters to be used.
{"title":"Comparison of different techniques for γH2AX/pH3 biomarkers quantification for chemical genotoxicity assessment","authors":"Cynthia Recoules , Chloé Huertas , Julien Vignard, Marc Audebert","doi":"10.1016/j.mrgentox.2025.503878","DOIUrl":"10.1016/j.mrgentox.2025.503878","url":null,"abstract":"<div><div>Chemical risk assessment relies on <em>in vitro</em> genotoxicity tests. Histone modifications (γH2AX and pH3) have emerged as valuable biomarkers for genotoxicity detection. In this study, we compared three parameters (global intensity, nuclear intensity, and foci number) for the γH2AX biomarker and two parameters (global intensity and % cell in mitosis) for the pH3 biomarker. These analyzes were performed in three cell lines: human osteosarcoma U2OS cells, human hepatocellular carcinoma HepG2 cells and rat intestinal epithelial IEC-6 cells. Cells were exposed for 24 h to four well-characterized hazardous substances: nocodazole (aneugen), etoposide (topoisomerase inhibitor), benzo[<em>a</em>]pyrene (DNA adducts inducer), and tunicamycin (apoptosis inducer). The Benchmark Concentration (BMC) approach indicated that the sensitivity of the technics varied depending on both the chemical compounds and the tested cell line. The γH2AX foci analysis provided the higher sensitivity for clastogenic compounds. For the aneugenic compound, the global intensity and the proportion of mitotic cells showed similar sensitivity. Following tunicamycin treatment, we only detected increase in γH2AX nuclear intensity in U2OS cell model, indicating that apoptosis does not interfere with γH2AX global intensity or foci number, thereby minimizing the risk of false positive results. Finally, we observed that compared to the other methods, global intensity permitted to monitor weaker fold inductions of the biomarkers. By comparing the different quantification methods of histone modifications used as genotoxicity biomarkers, this study highlights the most suitable parameters to be used.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"906 ","pages":"Article 503878"},"PeriodicalIF":2.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144704717","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 : 2025-08-01Epub Date: 2025-07-31DOI: 10.1016/j.mrgentox.2025.503881
Mohamed S.M. Attia , Mohammed A. Al-Hamamah , Sheikh F. Ahmad , Ahmed Nadeem , Saleh A. Bakheet , Mushtaq A. Ansari , Gamaleldin I. Harisa , Talha Bin Emran , Sabry M. Attia
Systemic lupus erythematosus (SLE) is a persistent autoimmune inflammatory disease associated with an elevated risk of kidney damage. The etiology of SLE remains unclear; nevertheless, current investigations increasingly indicate that increased DNA damage and deficiencies in the mechanisms of its repair might contribute to its pathogenesis, necessitating the identification and management of the disease. Therapies for SLE have improved considerably over recent decades. However, drugs that specifically address the underlying pathogenic pathways, such as potential DNA repair deficiencies, are unavailable. In this situation, drugs that ameliorate the altered DNA damage/repair might be a possible option for treating SLE. We investigated whether GW0742, an agonist of the peroxisome proliferator activator receptor β/δ, improves kidney function and ameliorates DNA damage/repair alteration in female lupus-prone mice. The results demonstrate that the repeated administration of GW0742 significantly ameliorates DNA damage/repair alteration in the bone marrow cells of lupus-prone animals, as assessed by the comet test. Furthermore, the administration of GW0742 restored the impaired DNA damage/repair pathway in lupus-prone mice by decreasing Gadd45a and p53 expression while elevating Ogg1 and Parp1 in the kidney tissues. The administration of GW0742 recovered the disturbed kidney redox balance in lupus-prone mice. It also ameliorated the altered biochemical markers related to lupus nephritis, as demonstrated by reduced levels of urinary protein and albumin, serum creatinine, and BUN. GW0742's protective outcome was verified by its ability to diminish the increased inflammatory marker MPO activity and ameliorated kidney histological characteristics of SLE. This suggests that GW0742 is a promising novel therapeutic agent for managing SLE and its associated complications.
{"title":"The PPAR-β/δ agonist GW0742 alleviates DNA damage and lupus nephritis in an animal model of systemic lupus erythematosus via restoring DNA repair gene expression","authors":"Mohamed S.M. Attia , Mohammed A. Al-Hamamah , Sheikh F. Ahmad , Ahmed Nadeem , Saleh A. Bakheet , Mushtaq A. Ansari , Gamaleldin I. Harisa , Talha Bin Emran , Sabry M. Attia","doi":"10.1016/j.mrgentox.2025.503881","DOIUrl":"10.1016/j.mrgentox.2025.503881","url":null,"abstract":"<div><div>Systemic lupus erythematosus (SLE) is a persistent autoimmune inflammatory disease associated with an elevated risk of kidney damage. The etiology of SLE remains unclear; nevertheless, current investigations increasingly indicate that increased DNA damage and deficiencies in the mechanisms of its repair might contribute to its pathogenesis, necessitating the identification and management of the disease. Therapies for SLE have improved considerably over recent decades. However, drugs that specifically address the underlying pathogenic pathways, such as potential DNA repair deficiencies, are unavailable. In this situation, drugs that ameliorate the altered DNA damage/repair might be a possible option for treating SLE. We investigated whether GW0742, an agonist of the peroxisome proliferator activator receptor β/δ, improves kidney function and ameliorates DNA damage/repair alteration in female lupus-prone mice. The results demonstrate that the repeated administration of GW0742 significantly ameliorates DNA damage/repair alteration in the bone marrow cells of lupus-prone animals, as assessed by the comet test. Furthermore, the administration of GW0742 restored the impaired DNA damage/repair pathway in lupus-prone mice by decreasing Gadd45a and p53 expression while elevating Ogg1 and Parp1 in the kidney tissues. The administration of GW0742 recovered the disturbed kidney redox balance in lupus-prone mice. It also ameliorated the altered biochemical markers related to lupus nephritis, as demonstrated by reduced levels of urinary protein and albumin, serum creatinine, and BUN. GW0742's protective outcome was verified by its ability to diminish the increased inflammatory marker MPO activity and ameliorated kidney histological characteristics of SLE. This suggests that GW0742 is a promising novel therapeutic agent for managing SLE and its associated complications.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"906 ","pages":"Article 503881"},"PeriodicalIF":2.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144773161","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}
The Ames assay is a bacterial reverse gene mutation test that has been a cornerstone of mutagenicity assessment. The emphasis now is on developing miniaturized versions of the Ames test in Petri dish to require less chemicals, reagents, and liver microsomal S9 fraction, thus reducing the number of test animals needed and to better comply with 3R principles. Miniaturized Ames assay versions promote high throughput testing of multiple samples during compound screening and facilitate the early exclusion of genotoxic agents during the product development process. Existing experimental data shed light on a high concordance between results gained with miniaturized Ames tests and the Petri dish-based method, yet further testing is required to corroborate these findings. We selected compounds with previously reported inconsistent outcomes and assessed their mutagenic potential using two miniaturized Ames assay formats, an agar-based 6-well plate test, and a liquid microplate fluctuation format assay. Investigation of dose-response curves of known mutagens with varying bacterial cell density inputs revealed that the sensitivity of the 6-well agar plate format might be increased by applying the right bacterial cell density. Our analysis indicates an overall good correlation between the results acquired with the two miniaturized Ames assay formats despite the conceptual characteristic differences in the assay paradigms. Furthermore, the miniaturized Ames assay formats could detect several chemicals as positive at lower concentrations than the Petri dish-based assay. Our findings indicate that the miniaturized Ames assay variations show promise as a reliable method for assessing chemical mutagenicity, while also aligning with environmentally friendly testing strategies. Finally, our results show that the miniaturized assays may exhibit increased sensitivity to impurities, potentially contributing to the observed discrepancies in the obtained results.
{"title":"Investigation of chemicals with inconsistent Ames results using miniaturized Ames test systems","authors":"Csaba Boglári, Cécile Koelbert, Nicole Weiland-Jaeggi","doi":"10.1016/j.mrgentox.2025.503874","DOIUrl":"10.1016/j.mrgentox.2025.503874","url":null,"abstract":"<div><div>The Ames assay is a bacterial reverse gene mutation test that has been a cornerstone of mutagenicity assessment. The emphasis now is on developing miniaturized versions of the Ames test in Petri dish to require less chemicals, reagents, and liver microsomal S9 fraction, thus reducing the number of test animals needed and to better comply with 3R principles. Miniaturized Ames assay versions promote high throughput testing of multiple samples during compound screening and facilitate the early exclusion of genotoxic agents during the product development process. Existing experimental data shed light on a high concordance between results gained with miniaturized Ames tests and the Petri dish-based method, yet further testing is required to corroborate these findings. We selected compounds with previously reported inconsistent outcomes and assessed their mutagenic potential using two miniaturized Ames assay formats, an agar-based 6-well plate test, and a liquid microplate fluctuation format assay. Investigation of dose-response curves of known mutagens with varying bacterial cell density inputs revealed that the sensitivity of the 6-well agar plate format might be increased by applying the right bacterial cell density. Our analysis indicates an overall good correlation between the results acquired with the two miniaturized Ames assay formats despite the conceptual characteristic differences in the assay paradigms. Furthermore, the miniaturized Ames assay formats could detect several chemicals as positive at lower concentrations than the Petri dish-based assay. Our findings indicate that the miniaturized Ames assay variations show promise as a reliable method for assessing chemical mutagenicity, while also aligning with environmentally friendly testing strategies. Finally, our results show that the miniaturized assays may exhibit increased sensitivity to impurities, potentially contributing to the observed discrepancies in the obtained results.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"906 ","pages":"Article 503874"},"PeriodicalIF":2.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663223","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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