Error-corrected next-generation sequencing (ecNGS) sensitively detects rare mutations in biological models. We applied Hawk-Seq™ to evaluate chemical-induced mutations using the IVGT TK6 human lymphoblastoid cell line. Since clonal and sub-clonal variants (CVs and SCVs) decrease mutation detection sensitivity, we first identified 4,501,430 CVs compared to GRCh38 by resequencing the TK6 genome. The overall base substitution (BS) frequency in vehicle controls after filtering out these variants was 2.0 × 10−6 base pairs (bp), relatively higher than in other ecNGS studies. A total of 4974 sites provided the same types of BSs in ≥ 2 vehicle controls, suggesting that SCVs increased the error frequency. After filtering out these sites, the overall background BS frequency significantly decreased (0.93 × 10−6 bp). Therefore, we filtered out the potential SCV positions identified using resequencing data with increased depth (mean depth of ca. 110), reducing the background overall BS frequency to 0.65 × 10−6 bp. Finally, we evaluated DNA samples from TK6 cells exposed to N-methyl-N-nitrosourea (MNU) and N-ethyl-N-nitrosourea (ENU) for 24 h. The overall BS frequencies in MNU- and ENU-treated samples were 9.0 × 10−6 and 2.0 × 10−6 bp, respectively, significantly improving the signal-to-noise ratio. MNU predominantly induced G:C > A:T (21 × 10−6 bp), 62 times higher than that induced by vehicle controls. ENU primarily induced G:C > A:T (2.7 × 10−6 bp) and significantly increased A:T > C:G and A:T > G:C frequencies (∼10−7 bp). Our method sensitively detected mutations, including minor patterns, indicating its potential to reflect various mutagenic mechanisms.
{"title":"Genome-wide mutation analysis induced by mutagens in TK6 cells using Hawk-Seq™","authors":"Yuki Otsubo , Takako Hirose , Shoji Matsumura , Sayaka Hosoi , Kazutoshi Saito , Masaaki Miyazawa","doi":"10.1016/j.mrgentox.2025.503875","DOIUrl":"10.1016/j.mrgentox.2025.503875","url":null,"abstract":"<div><div>Error-corrected next-generation sequencing (ecNGS) sensitively detects rare mutations in biological models. We applied Hawk-Seq™ to evaluate chemical-induced mutations using the IVGT TK6 human lymphoblastoid cell line. Since clonal and sub-clonal variants (CVs and SCVs) decrease mutation detection sensitivity, we first identified 4,501,430 CVs compared to GRCh38 by resequencing the TK6 genome. The overall base substitution (BS) frequency in vehicle controls after filtering out these variants was 2.0 × 10<sup>−6</sup> base pairs (bp), relatively higher than in other ecNGS studies. A total of 4974 sites provided the same types of BSs in ≥ 2 vehicle controls, suggesting that SCVs increased the error frequency. After filtering out these sites, the overall background BS frequency significantly decreased (0.93 × 10<sup>−6</sup> bp). Therefore, we filtered out the potential SCV positions identified using resequencing data with increased depth (mean depth of ca. 110), reducing the background overall BS frequency to 0.65 × 10<sup>−6</sup> bp. Finally, we evaluated DNA samples from TK6 cells exposed to <em>N</em>-methyl-<em>N</em>-nitrosourea (MNU) and <em>N</em>-ethyl-<em>N</em>-nitrosourea (ENU) for 24 h. The overall BS frequencies in MNU- and ENU-treated samples were 9.0 × 10<sup>−6</sup> and 2.0 × 10<sup>−6</sup> bp, respectively, significantly improving the signal-to-noise ratio. MNU predominantly induced G:C > A:T (21 × 10<sup>−6</sup> bp), 62 times higher than that induced by vehicle controls. ENU primarily induced G:C > A:T (2.7 × 10<sup>−6</sup> bp) and significantly increased A:T > C:G and A:T > G:C frequencies (∼10<sup>−7</sup> bp). Our method sensitively detected mutations, including minor patterns, indicating its potential to reflect various mutagenic mechanisms.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"905 ","pages":"Article 503875"},"PeriodicalIF":2.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144654211","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 : 2025-07-01DOI: 10.1016/j.mrgentox.2025.503877
Andrea G. Cardozo , Daniel C. Castrogiovanni , Julieta M. Parisi , Alejandro D. Bolzán
The induction of telomere dysfunction-related chromosomal aberrations by the radiomimetic antibiotic bleomycin (BLM) was studied in human lymphoblastoid cells immortalized with the Epstein-Barr virus (EBV). To this end, an EBV-induced lymphoblastoid cell line (T-37) was exposed to increased concentrations of BLM (10–100 µg/mL) for 2 h at 37ºC, and telomere aberrations were analyzed 24 h (first mitosis) after treatment using PNA-FISH with pan-telomeric plus pan-centromeric probes. Telomere signal duplications (TSD) increased significantly in BLM-exposed cells (p < 0.01), although the concentration-response relationship was non-linear. Most of the induced TSD (95–99 %) were of chromatid-type. No induction of telomere signal loss, telomere fusions or telomere associations by BLM was observed in T-37 cells. These findings show that BLM induces short-term telomere dysfunction in EBV-transformed human lymphoblastoid cells in the form of TSD (which implies telomere fragility) and suggest that these effects mainly occur during the G2 stage of the cell cycle. The persistence of this type of aberrations in the long-term in EBV-induced lymphoblastoid cells and other human cells exposed to BLM may be of medical relevance. Telomere fragility induced by BLM could promote genomic instability, which might contribute to the development of secondary tumors in patients undergoing chemotherapy based on this compound. Consequently, our study raises concerns about the potential long-term genomic effects of BLM in treated patients and suggests that the analysis of TSD could be a useful biomarker for detecting BLM-induced telomere dysfunction in human cells.
{"title":"Bleomycin induces short-term telomere fragility in Epstein-Barr virus-transformed human lymphoblastoid cells","authors":"Andrea G. Cardozo , Daniel C. Castrogiovanni , Julieta M. Parisi , Alejandro D. Bolzán","doi":"10.1016/j.mrgentox.2025.503877","DOIUrl":"10.1016/j.mrgentox.2025.503877","url":null,"abstract":"<div><div>The induction of telomere dysfunction-related chromosomal aberrations by the radiomimetic antibiotic bleomycin (BLM) was studied in human lymphoblastoid cells immortalized with the Epstein-Barr virus (EBV). To this end, an EBV-induced lymphoblastoid cell line (T-37) was exposed to increased concentrations of BLM (10–100 µg/mL) for 2 h at 37ºC, and telomere aberrations were analyzed 24 h (first mitosis) after treatment using PNA-FISH with pan-telomeric plus pan-centromeric probes. Telomere signal duplications (TSD) increased significantly in BLM-exposed cells (p < 0.01), although the concentration-response relationship was non-linear. Most of the induced TSD (95–99 %) were of chromatid-type. No induction of telomere signal loss, telomere fusions or telomere associations by BLM was observed in T-37 cells. These findings show that BLM induces short-term telomere dysfunction in EBV-transformed human lymphoblastoid cells in the form of TSD (which implies telomere fragility) and suggest that these effects mainly occur during the G2 stage of the cell cycle. The persistence of this type of aberrations in the long-term in EBV-induced lymphoblastoid cells and other human cells exposed to BLM may be of medical relevance. Telomere fragility induced by BLM could promote genomic instability, which might contribute to the development of secondary tumors in patients undergoing chemotherapy based on this compound. Consequently, our study raises concerns about the potential long-term genomic effects of BLM in treated patients and suggests that the analysis of TSD could be a useful biomarker for detecting BLM-induced telomere dysfunction in human cells.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"905 ","pages":"Article 503877"},"PeriodicalIF":2.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144654210","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 : 2025-06-12DOI: 10.1016/j.mrgentox.2025.503872
Serap Yüce Emiroğlu , Tülay Aşkın Çeli̇k
Objective
This study aimed to assess the genotoxic effects of chronic occupational exposure to low-dose ionizing radiation among healthcare professionals employed at three hospitals in Aydın, Turkey: Aydın Adnan Menderes University Research and Application Hospital (ADU-UAH), Atatürk State Hospital, and Aydın State Hospital. The exposed group comprised 27 healthcare workers routinely operating in radiation-related departments, while 27 matched individuals with no known exposure constituted the control group.
Methods
Genetic damage was evaluated using the exfoliated buccal micronucleus cytome (BMCyt) assay, a validated and non-invasive method for human biomonitoring. Frequencies of nuclear abnormalities—including micronuclei, binucleated cells, nuclear buds, condensed chromatin, karyorrhexis, karyolysis, and pyknotic cells—were systematically recorded and compared between groups.
Results
A statistically significant increase in all genotoxic markers was observed in the exposed group compared to controls (p < 0.05). The highest frequency of micronucleated cells was found in workers at Aydın State Hospital (32.38 ‰), approximately 30-fold higher than the control group (2.84 ‰). Healthcare workers at ADU-UAH and Atatürk State Hospital exhibited moderate yet notable elevations, with frequencies of 24.85 ‰ and 17.28 ‰, respectively. Sex-stratified analysis revealed minor but statistically significant differences, with male workers showing slightly higher genotoxicity levels (p < 0.05), although female staff exhibited higher nuclear anomalies at certain institutions.
Conclusion
Our findings indicate that chronic exposure to low-dose ionizing radiation is associated with increased genomic instability among healthcare workers. The elevated frequency of nuclear abnormalities highlights a potential long-term mutagenic risk in occupational settings. These results underscore the urgent need for reinforced radiation safety protocols, routine biomonitoring, and institutional policy revisions to mitigate genotoxic risks. Further studies are warranted to elucidate the mechanisms underlying radiation-induced genomic damage and to better understand individual susceptibility patterns in exposed populations.
{"title":"Radiology personnel chronically exposed to low-dose ionizing radiation: Assessment of genotoxic damage with the buccal micronucleus cytome assay","authors":"Serap Yüce Emiroğlu , Tülay Aşkın Çeli̇k","doi":"10.1016/j.mrgentox.2025.503872","DOIUrl":"10.1016/j.mrgentox.2025.503872","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to assess the genotoxic effects of chronic occupational exposure to low-dose ionizing radiation among healthcare professionals employed at three hospitals in Aydın, Turkey: Aydın Adnan Menderes University Research and Application Hospital (ADU-UAH), Atatürk State Hospital, and Aydın State Hospital. The exposed group comprised 27 healthcare workers routinely operating in radiation-related departments, while 27 matched individuals with no known exposure constituted the control group.</div></div><div><h3>Methods</h3><div>Genetic damage was evaluated using the exfoliated buccal micronucleus cytome (BMCyt) assay, a validated and non-invasive method for human biomonitoring. Frequencies of nuclear abnormalities—including micronuclei, binucleated cells, nuclear buds, condensed chromatin, karyorrhexis, karyolysis, and pyknotic cells—were systematically recorded and compared between groups.</div></div><div><h3>Results</h3><div>A statistically significant increase in all genotoxic markers was observed in the exposed group compared to controls (p < 0.05). The highest frequency of micronucleated cells was found in workers at Aydın State Hospital (32.38 ‰), approximately 30-fold higher than the control group (2.84 ‰). Healthcare workers at ADU-UAH and Atatürk State Hospital exhibited moderate yet notable elevations, with frequencies of 24.85 ‰ and 17.28 ‰, respectively. Sex-stratified analysis revealed minor but statistically significant differences, with male workers showing slightly higher genotoxicity levels (p < 0.05), although female staff exhibited higher nuclear anomalies at certain institutions.</div></div><div><h3>Conclusion</h3><div>Our findings indicate that chronic exposure to low-dose ionizing radiation is associated with increased genomic instability among healthcare workers. The elevated frequency of nuclear abnormalities highlights a potential long-term mutagenic risk in occupational settings. These results underscore the urgent need for reinforced radiation safety protocols, routine biomonitoring, and institutional policy revisions to mitigate genotoxic risks. Further studies are warranted to elucidate the mechanisms underlying radiation-induced genomic damage and to better understand individual susceptibility patterns in exposed populations.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"905 ","pages":"Article 503872"},"PeriodicalIF":2.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144290487","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}
Arsenic and bisphenol A (BPA) are widespread environmental pollutants. We have studied the nephrotoxicity of arsenite (ARS), 10 mg/L in drinking water, plus BPA, 50 µg/kg oral dose, in juvenile Sprague-Dawley rats. Animals were randomized into seven groups and exposed to the chemicals either continuously or intermittently, for 8 weeks. The parameters evaluated were urine biomarkers, histopathological and transmission electron microscopic (TEM) examinations, DNA damage (halo assay), and protein expressions. Continuous exposure to AS and BPA significantly increased urinary creatinine, albumin, and total protein, and decreased blood urea nitrogen (BUN). Histopathological and TEM data showed brush border detachment, iron accumulation, podocyte injury, increased slit diaphragm space, and collagen deposition in both exposure groups. Significantly greater DNA damage was seen in the combined-exposure group than in the other experimental groups. Combination exposure in the continuous and intermittent groups showed renal fibrosis and ferroptosis and gene expression analysis revealed a significant increase in Bax and decrease in SIRT 1. Combination exposure was more harmful than the individual exposures in causing kidney injury in these animals.
{"title":"Low-dose bisphenol A plus arsenite: Continuous or intermittent exposures in Sprague-Dawley rats; Effects on kidney oxidative stress, DNA damage, ferroptosis, and fibrosis","authors":"Girija Prasanna Sahoo, Asutosh Pattnaik, Vinod Kumar, Gopabandhu Jena","doi":"10.1016/j.mrgentox.2025.503871","DOIUrl":"10.1016/j.mrgentox.2025.503871","url":null,"abstract":"<div><div>Arsenic and bisphenol A (BPA) are widespread environmental pollutants. We have studied the nephrotoxicity of arsenite (ARS), 10 mg/L in drinking water, plus BPA, 50 µg/kg oral dose, in juvenile Sprague-Dawley rats. Animals were randomized into seven groups and exposed to the chemicals either continuously or intermittently, for 8 weeks. The parameters evaluated were urine biomarkers, histopathological and transmission electron microscopic (TEM) examinations, DNA damage (halo assay), and protein expressions. Continuous exposure to AS and BPA significantly increased urinary creatinine, albumin, and total protein, and decreased blood urea nitrogen (BUN). Histopathological and TEM data showed brush border detachment, iron accumulation, podocyte injury, increased slit diaphragm space, and collagen deposition in both exposure groups. Significantly greater DNA damage was seen in the combined-exposure group than in the other experimental groups. Combination exposure in the continuous and intermittent groups showed renal fibrosis and ferroptosis and gene expression analysis revealed a significant increase in Bax and decrease in SIRT 1. Combination exposure was more harmful than the individual exposures in causing kidney injury in these animals.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"904 ","pages":"Article 503871"},"PeriodicalIF":2.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887582","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 : 2025-04-23DOI: 10.1016/j.mrgentox.2025.503870
Bruna Alves Alonso Martins , Ana Leticia Hilario Garcia , Malu Siqueira Borges , Daiane Dias Ribeiro Nobles , Alana Witt Hansen , Fernando Rosado Spilki , Lavínia Schuler-Faccini , Pabulo Henrique Rampelotto , Juliana da Silva
The long-term effects of COVID-19 infection on genomic integrity, along with hematological, biochemical, and inflammatory, remain poorly understood. Viral infections, including SARS-CoV-2, are known to induce genomic instability, potentially contributing to the persistence of post-COVID-19 symptoms. This study aimed to assess genomic instability in individuals with acute and chronic post-COVID-19 conditions, alongside hematological profiles, metabolic parameters, and inflammatory markers, compared to a SARS-CoV-2-negative control group. Participants (n = 231) from southern Brazil were stratified into acute post-COVID (n = 78), chronic post-COVID (n = 79), and control groups (n = 74). DNA damage was assessed using alkaline and enzyme-modified comet assays. Oxidative lesions were detected across all groups, but no significant differences were observed among them. Correlations with biochemical markers suggest inflammation and oxidative stress as central mechanisms in post-COVID-19 pathophysiology. Hematological and biochemical analyses revealed persistent inflammation, lipid metabolism disruptions, and gender-specific alterations, such as higher levels of inflammatory markers (C-reactive protein and ferritin) and lipid abnormalities in men, whereas women exhibited distinct hematological patterns. Age-related influences on metabolic and inflammatory markers further illustrate the systemic complexity of post-COVID-19 effects. The chronic group exhibited ongoing but attenuated markers of inflammation and oxidative stress compared to the acute group. These findings suggest that genetic instability alone may not fully explain the observed clinical manifestations, emphasizing the role of persistent inflammation and metabolic dysregulation. This study provides a comprehensive view of the interplay between genomic instability, inflammation, oxidative damage, and systemic alterations in post-COVID-19 condition. It underscores the importance of a multifaceted approach to understanding disease mechanisms and the need for longitudinal studies to explore the dynamic nature of these alterations and their long-term health implications.
{"title":"Acute and chronic post-COVID-19 conditions: A study of genetic integrity and clinical markers","authors":"Bruna Alves Alonso Martins , Ana Leticia Hilario Garcia , Malu Siqueira Borges , Daiane Dias Ribeiro Nobles , Alana Witt Hansen , Fernando Rosado Spilki , Lavínia Schuler-Faccini , Pabulo Henrique Rampelotto , Juliana da Silva","doi":"10.1016/j.mrgentox.2025.503870","DOIUrl":"10.1016/j.mrgentox.2025.503870","url":null,"abstract":"<div><div>The long-term effects of COVID-19 infection on genomic integrity, along with hematological, biochemical, and inflammatory, remain poorly understood. Viral infections, including SARS-CoV-2, are known to induce genomic instability, potentially contributing to the persistence of post-COVID-19 symptoms. This study aimed to assess genomic instability in individuals with acute and chronic post-COVID-19 conditions, alongside hematological profiles, metabolic parameters, and inflammatory markers, compared to a SARS-CoV-2-negative control group. Participants (n = 231) from southern Brazil were stratified into acute post-COVID (n = 78), chronic post-COVID (n = 79), and control groups (n = 74). DNA damage was assessed using alkaline and enzyme-modified comet assays. Oxidative lesions were detected across all groups, but no significant differences were observed among them. Correlations with biochemical markers suggest inflammation and oxidative stress as central mechanisms in post-COVID-19 pathophysiology. Hematological and biochemical analyses revealed persistent inflammation, lipid metabolism disruptions, and gender-specific alterations, such as higher levels of inflammatory markers (C-reactive protein and ferritin) and lipid abnormalities in men, whereas women exhibited distinct hematological patterns. Age-related influences on metabolic and inflammatory markers further illustrate the systemic complexity of post-COVID-19 effects. The chronic group exhibited ongoing but attenuated markers of inflammation and oxidative stress compared to the acute group. These findings suggest that genetic instability alone may not fully explain the observed clinical manifestations, emphasizing the role of persistent inflammation and metabolic dysregulation. This study provides a comprehensive view of the interplay between genomic instability, inflammation, oxidative damage, and systemic alterations in post-COVID-19 condition. It underscores the importance of a multifaceted approach to understanding disease mechanisms and the need for longitudinal studies to explore the dynamic nature of these alterations and their long-term health implications.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"904 ","pages":"Article 503870"},"PeriodicalIF":2.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877408","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 : 2025-04-12DOI: 10.1016/j.mrgentox.2025.503869
Gyöngyi Farkas , Réka Király , Gábor Székely , Zsuzsa S. Kocsis , Gyöngyvér Orsolya Sándor , Csilla Pesznyák , Tibor Major , Zoltán-Takácsi Nagy , Zsolt Jurányi
Cytogenetic analysis of blood lymphocytes can be used as a biomarker of absorbed radiation dose. The frequency of chromosomal aberrations (CA) correlates with subsequent cancer incidence. Healthy medical employees in Hungary - 301 working in an ionizing radiation work area and 732 controls - were studied from 1997 to 2022. Frequencies of chromatid- and chromosome-type aberrations in peripheral blood lymphocytes were significantly higher in the ionizing radiation group. Smoking also affected the frequency of aberrations, which was highest among smokers in the radiation group. Staff working with ionizing radiation were divided into four groups: CT, radiation therapy, diagnostic X-ray, and nuclear medicine. Total aberrations and aberrant cells were significantly higher in the nuclear medicine group than in the CT group. Tumor cases were not more frequent among the ionizing radiation group than among the control group.
{"title":"A study of radiation workers: Dosimetry, chromosomal aberrations, and cancer risk","authors":"Gyöngyi Farkas , Réka Király , Gábor Székely , Zsuzsa S. Kocsis , Gyöngyvér Orsolya Sándor , Csilla Pesznyák , Tibor Major , Zoltán-Takácsi Nagy , Zsolt Jurányi","doi":"10.1016/j.mrgentox.2025.503869","DOIUrl":"10.1016/j.mrgentox.2025.503869","url":null,"abstract":"<div><div>Cytogenetic analysis of blood lymphocytes can be used as a biomarker of absorbed radiation dose. The frequency of chromosomal aberrations (CA) correlates with subsequent cancer incidence. Healthy medical employees in Hungary - 301 working in an ionizing radiation work area and 732 controls - were studied from 1997 to 2022. Frequencies of chromatid- and chromosome-type aberrations in peripheral blood lymphocytes were significantly higher in the ionizing radiation group. Smoking also affected the frequency of aberrations, which was highest among smokers in the radiation group. Staff working with ionizing radiation were divided into four groups: CT, radiation therapy, diagnostic X-ray, and nuclear medicine. Total aberrations and aberrant cells were significantly higher in the nuclear medicine group than in the CT group. Tumor cases were not more frequent among the ionizing radiation group than among the control group.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"904 ","pages":"Article 503869"},"PeriodicalIF":2.3,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834251","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 : 2025-03-30DOI: 10.1016/j.mrgentox.2025.503867
Arno C. Gutleb , Sivakumar Murugadoss , Maciej Stępnik , Tanima SenGupta , Naouale El Yamani , Eleonora Marta Longhin , Ann-Karin Hardie Olsen , Ewelina Wyrzykowska , Karolina Jagiello , Beata Judzinska , Sebastien Cambier , Tatiana Honza , Erin McFadden , Sergey Shaposhnikov , Tomasz Puzyn , Tommaso Serchi , Pamina Weber , Emma Arnesdotter , Vier Skakalova , Katerina Jirsova , Maria Dusinska
Genotoxicity assessment is essential for ensuring chemical safety and mitigating risks to human health and the environment. Traditional methods, reliant on animal models, are time-consuming, costly, and raise ethical concerns. New Approach Methods (NAMs) offer innovative, cost-effective, and ethical alternatives, playing a pivotal role in both traditional and next-generation risk assessment (NGRA) by minimizing the need for animal testing, particularly in genotoxicity evaluations. However, the development of NAMs often overlooks the particular physicochemical properties of nanomaterials (NMs), which significantly influence their toxicological behaviour and can interfere with genotoxicity evaluation. This underscores an urgent need for the standardization and adaptation of NAMs to address nano- and advanced material-specific genotoxicity challenges. In this review, we summarize the challenges associated with genotoxicity testing of NMs and highlight the suitability of existing in vitro and in silico NAMs for NMs and advanced materials, enabling genotoxicity testing across various exposure routes and organ systems. Despite considerable progress, regulatory validation remains constrained by the absence of approved test guidelines and standardized protocols. To achieve regulatory acceptance, it is crucial to adapt NAMs to NM-specific exposure scenarios, refine test systems to better mimic human biology, develop tailored in vitro protocols, and ensure thorough characterisation of NMs both in pristine form and dispersed in culture medium. Collaborative efforts among scientists, regulators, industry, and advocacy groups are vital to improving the reliability and regulatory acceptance of NAMs. By addressing these challenges, NAMs have the potential to revolutionize genotoxicity risk assessment, advancing it towards a more sustainable, efficient and ethical framework.
{"title":"New Approach Methods (NAMs) for genotoxicity assessment of nano- and advanced materials; Advantages and challenges","authors":"Arno C. Gutleb , Sivakumar Murugadoss , Maciej Stępnik , Tanima SenGupta , Naouale El Yamani , Eleonora Marta Longhin , Ann-Karin Hardie Olsen , Ewelina Wyrzykowska , Karolina Jagiello , Beata Judzinska , Sebastien Cambier , Tatiana Honza , Erin McFadden , Sergey Shaposhnikov , Tomasz Puzyn , Tommaso Serchi , Pamina Weber , Emma Arnesdotter , Vier Skakalova , Katerina Jirsova , Maria Dusinska","doi":"10.1016/j.mrgentox.2025.503867","DOIUrl":"10.1016/j.mrgentox.2025.503867","url":null,"abstract":"<div><div>Genotoxicity assessment is essential for ensuring chemical safety and mitigating risks to human health and the environment. Traditional methods, reliant on animal models, are time-consuming, costly, and raise ethical concerns. New Approach Methods (NAMs) offer innovative, cost-effective, and ethical alternatives, playing a pivotal role in both traditional and next-generation risk assessment (NGRA) by minimizing the need for animal testing, particularly in genotoxicity evaluations. However, the development of NAMs often overlooks the particular physicochemical properties of nanomaterials (NMs), which significantly influence their toxicological behaviour and can interfere with genotoxicity evaluation. This underscores an urgent need for the standardization and adaptation of NAMs to address nano- and advanced material-specific genotoxicity challenges. In this review, we summarize the challenges associated with genotoxicity testing of NMs and highlight the suitability of existing <em>in vitro</em> and <em>in silico</em> NAMs for NMs and advanced materials, enabling genotoxicity testing across various exposure routes and organ systems. Despite considerable progress, regulatory validation remains constrained by the absence of approved test guidelines and standardized protocols. To achieve regulatory acceptance, it is crucial to adapt NAMs to NM-specific exposure scenarios, refine test systems to better mimic human biology, develop tailored <em>in vitro</em> protocols, and ensure thorough characterisation of NMs both in pristine form and dispersed in culture medium. Collaborative efforts among scientists, regulators, industry, and advocacy groups are vital to improving the reliability and regulatory acceptance of NAMs. By addressing these challenges, NAMs have the potential to revolutionize genotoxicity risk assessment, advancing it towards a more sustainable, efficient and ethical framework.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"904 ","pages":"Article 503867"},"PeriodicalIF":2.3,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768376","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 : 2025-03-23DOI: 10.1016/j.mrgentox.2025.503866
Ebru Yayla , Cem Guler , Aylin Buhur , Nefise Ulku Karabay Yavasoglu , Selma Katalay , Cinel Koksal Karayildirim
In the current study, the relationship between DNA damage and heavy metal pollutions was evaluated by sampling mussels from Izmir Bay (Turkey), which has different anthropogenic impacts in the Aegean Sea. M. galloprovincialis was selected as a bioindicator organism to determine the heavy metal amounts, SOD, CAT, TBARS levels and to detect the DNA damage in 4 different stations of Izmir Bay. A significant increase was detected in all heavy metals in the digestive gland tissue of the mussels collected from the Alsancak in summer compared to spring. Especially, Zn levels of gills and digestive glands of mussels collected from Alsancak in summer were detected 22.411 and 40.447 μg/g, respectively. According to MPI values, significant differences were determined in Urla and the highest accumulation was calculated in gill tissue. The activities of SOD and CAT enzymes were found at a very high level in mussel gills and glands at all stations except Urla in summer compared to them in spring. Additionally, TBARS levels were higher in mussel gills and gonad tissues at Inciralti and Urla stations in summer compared to spring samples. DNA damage classification in mussel hemocytes from all stations was identified according to the Comet assay. The test results showed that a statistically significant decrease in DNA% in comet tails in hemocytes of mussels collected from all stations in Summer was found compared to them in Spring. Also, at all stations except Alsancak, the genetic damage index decreased in summer compared to spring. While a positive correlation was detected between heavy metal pollution and DNA damage in mussels taken from Alsancak and Inciraltı (r = 0.734), a significant correlation was detected in Pasaport and Urla in both seasons (r = 0.999). This study indicates that heavy metal contaminations in the mussels of Izmir Bay are still an environmental problem on this area. DNA damage is an appropriate biomarker for genotoxicity evaluation even in low heavy metal contaminated areas.
{"title":"DNA damage and oxidative stress responses to pollution of Mytilus galloprovincialis L. from the Izmir Bay (Turkey): Seasonal evaluation","authors":"Ebru Yayla , Cem Guler , Aylin Buhur , Nefise Ulku Karabay Yavasoglu , Selma Katalay , Cinel Koksal Karayildirim","doi":"10.1016/j.mrgentox.2025.503866","DOIUrl":"10.1016/j.mrgentox.2025.503866","url":null,"abstract":"<div><div>In the current study, the relationship between DNA damage and heavy metal pollutions was evaluated by sampling mussels from Izmir Bay (Turkey), which has different anthropogenic impacts in the Aegean Sea. <em>M. galloprovincialis</em> was selected as a bioindicator organism to determine the heavy metal amounts, SOD, CAT, TBARS levels and to detect the DNA damage in 4 different stations of Izmir Bay. A significant increase was detected in all heavy metals in the digestive gland tissue of the mussels collected from the Alsancak in summer compared to spring. Especially, Zn levels of gills and digestive glands of mussels collected from Alsancak in summer were detected 22.411 and 40.447 μg/g, respectively. According to MPI values, significant differences were determined in Urla and the highest accumulation was calculated in gill tissue. The activities of SOD and CAT enzymes were found at a very high level in mussel gills and glands at all stations except Urla in summer compared to them in spring. Additionally, TBARS levels were higher in mussel gills and gonad tissues at Inciralti and Urla stations in summer compared to spring samples. DNA damage classification in mussel hemocytes from all stations was identified according to the Comet assay. The test results showed that a statistically significant decrease in DNA% in comet tails in hemocytes of mussels collected from all stations in Summer was found compared to them in Spring. Also, at all stations except Alsancak, the genetic damage index decreased in summer compared to spring. While a positive correlation was detected between heavy metal pollution and DNA damage in mussels taken from Alsancak and Inciraltı (r = 0.734), a significant correlation was detected in Pasaport and Urla in both seasons (r = 0.999). This study indicates that heavy metal contaminations in the mussels of Izmir Bay are still an environmental problem on this area. DNA damage is an appropriate biomarker for genotoxicity evaluation even in low heavy metal contaminated areas.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"904 ","pages":"Article 503866"},"PeriodicalIF":2.3,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768375","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 : 2025-03-05DOI: 10.1016/j.mrgentox.2025.503865
Yuxin Liu, Peter Møller , Martin Roursgaard
Plastic is used extensively worldwide. However, plastic particles that are less than 1000 nm (i.e. nanoplastics) may be hazardous to human cells. Nanoplastics might be manufactured intentionally or be formed in the environment by degradation of larger plastic items. Ingestion and inhalation are the two most common routes of human exposure to nanoplastics, indicating that epithelial cells have direct exposure. However, immune cells will also interact with particles during tissue inflammation. An assessment of published studies suggests that polystyrene (PS) particles generate higher levels of DNA damage in immune cells compared to epithelial cells, although it has not been formally studied under the same experimental condition. To investigate this, we assessed cytotoxicity, oxidative stress and DNA strand breaks in lung epithelial (A549) cells, intestinal epithelial (Caco-2) cells, and two monocytes (THP-1 and U937) after exposure to amine-functionalized polystyrene particles (PS-NH2) with declared particle size of 240 nm. No cytotoxicity or intracellular reactive oxygen species production were found at concentrations up to 200 µg/mL. Exposure to PS-NH2 was associated with glutathione depletion in A549 cells. However, there was no increase in the level of DNA strand breaks, measured by the comet assay, in any of the cell lines under standard assay conditions. Diethyl maleate treatment was used to render cells susceptible to oxidative stress. By itself, diethyl maleate treatment led to approximately 50 % glutathione depletion and increased DNA strand breaks, but additional DNA damage was not observed in cells by PS-NH2 exposure in A549, Caco-2, THP-1 and U937 cells.
{"title":"Aminated polystyrene and DNA strand breaks in A549, Caco-2, THP-1 and U937 human cell lines","authors":"Yuxin Liu, Peter Møller , Martin Roursgaard","doi":"10.1016/j.mrgentox.2025.503865","DOIUrl":"10.1016/j.mrgentox.2025.503865","url":null,"abstract":"<div><div>Plastic is used extensively worldwide. However, plastic particles that are less than 1000 nm (i.e. nanoplastics) may be hazardous to human cells. Nanoplastics might be manufactured intentionally or be formed in the environment by degradation of larger plastic items. Ingestion and inhalation are the two most common routes of human exposure to nanoplastics, indicating that epithelial cells have direct exposure. However, immune cells will also interact with particles during tissue inflammation. An assessment of published studies suggests that polystyrene (PS) particles generate higher levels of DNA damage in immune cells compared to epithelial cells, although it has not been formally studied under the same experimental condition. To investigate this, we assessed cytotoxicity, oxidative stress and DNA strand breaks in lung epithelial (A549) cells, intestinal epithelial (Caco-2) cells, and two monocytes (THP-1 and U937) after exposure to amine-functionalized polystyrene particles (PS-NH<sub>2</sub>) with declared particle size of 240 nm. No cytotoxicity or intracellular reactive oxygen species production were found at concentrations up to 200 µg/mL. Exposure to PS-NH<sub>2</sub> was associated with glutathione depletion in A549 cells. However, there was no increase in the level of DNA strand breaks, measured by the comet assay, in any of the cell lines under standard assay conditions. Diethyl maleate treatment was used to render cells susceptible to oxidative stress. By itself, diethyl maleate treatment led to approximately 50 % glutathione depletion and increased DNA strand breaks, but additional DNA damage was not observed in cells by PS-NH<sub>2</sub> exposure in A549, Caco-2, THP-1 and U937 cells.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"903 ","pages":"Article 503865"},"PeriodicalIF":2.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143576939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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