Mutation research. Genetic toxicology and environmental mutagenesis最新文献

{"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,&nbsp;Asutosh Pattnaik,&nbsp;Vinod Kumar,&nbsp;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}

{"title":"Acute and chronic post-COVID-19 conditions: A study of genetic integrity and clinical markers","authors":"Bruna Alves Alonso Martins ,&nbsp;Ana Leticia Hilario Garcia ,&nbsp;Malu Siqueira Borges ,&nbsp;Daiane Dias Ribeiro Nobles ,&nbsp;Alana Witt Hansen ,&nbsp;Fernando Rosado Spilki ,&nbsp;Lavínia Schuler-Faccini ,&nbsp;Pabulo Henrique Rampelotto ,&nbsp;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}

{"title":"A study of radiation workers: Dosimetry, chromosomal aberrations, and cancer risk","authors":"Gyöngyi Farkas ,&nbsp;Réka Király ,&nbsp;Gábor Székely ,&nbsp;Zsuzsa S. Kocsis ,&nbsp;Gyöngyvér Orsolya Sándor ,&nbsp;Csilla Pesznyák ,&nbsp;Tibor Major ,&nbsp;Zoltán-Takácsi Nagy ,&nbsp;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}

{"title":"New Approach Methods (NAMs) for genotoxicity assessment of nano- and advanced materials; Advantages and challenges","authors":"Arno C. Gutleb ,&nbsp;Sivakumar Murugadoss ,&nbsp;Maciej Stępnik ,&nbsp;Tanima SenGupta ,&nbsp;Naouale El Yamani ,&nbsp;Eleonora Marta Longhin ,&nbsp;Ann-Karin Hardie Olsen ,&nbsp;Ewelina Wyrzykowska ,&nbsp;Karolina Jagiello ,&nbsp;Beata Judzinska ,&nbsp;Sebastien Cambier ,&nbsp;Tatiana Honza ,&nbsp;Erin McFadden ,&nbsp;Sergey Shaposhnikov ,&nbsp;Tomasz Puzyn ,&nbsp;Tommaso Serchi ,&nbsp;Pamina Weber ,&nbsp;Emma Arnesdotter ,&nbsp;Vier Skakalova ,&nbsp;Katerina Jirsova ,&nbsp;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}

{"title":"DNA damage and oxidative stress responses to pollution of Mytilus galloprovincialis L. from the Izmir Bay (Turkey): Seasonal evaluation","authors":"Ebru Yayla ,&nbsp;Cem Guler ,&nbsp;Aylin Buhur ,&nbsp;Nefise Ulku Karabay Yavasoglu ,&nbsp;Selma Katalay ,&nbsp;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}

{"title":"Aminated polystyrene and DNA strand breaks in A549, Caco-2, THP-1 and U937 human cell lines","authors":"Yuxin Liu,&nbsp;Peter Møller ,&nbsp;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-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.</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}

{"title":"The dose-, LET-, and gene-dependent patterns of intragenic DNA changes underlying recessive visible mutations at the autosomal gene cinnabar of Drosophila melanogaster","authors":"I.D. Alexandrov,&nbsp;M.V. Alexandrova,&nbsp;K.P. Afanasyeva,&nbsp;N.E. Kharchenko","doi":"10.1016/j.mrgentox.2025.503857","DOIUrl":"10.1016/j.mrgentox.2025.503857","url":null,"abstract":"<div><div>Sequence analysis of 2 spontaneous, 26 γ-ray- and 10 neutron/neutron + γ-ray-induced <em>cn</em> gene/point mutants was performed. One spontaneous mutant had the entire maternal <em>сn</em>^<em>1</em> sequence studied (4644 bp, full gene conversion). The second mutant contained cluster of DNA changes consisting of a partial gene conversion (tract length of 1087 bp), as well as an extended deletion (47 bp) and one single-base substitution in exon 2. Almost the same spectra of DNA changes in γ-ray- and neutron/neutron + γ-ray-induced <em>cn</em> mutants made it possible to unite them into one group of 36 radiation-induced mutants. Among the 36 mutants studied, 5 mutants (13.9 %) did’t have any DNA changes within the studied sequence of the <em>cn</em> genomic region. The 31 remaining mutants contained 36 DNA changes. There were 3 (8.3 %) single-base substitutions, 2 (5.5 %) frameshifts or indels 1–3-bp long, 14 (38.9 %) extended deletions of 5–21 bp in length, 12 (33.3 %) gene conversion events, 2 (5.5 %) large insertion (∼ 6.0 kb) of unidentified origin, and 1 (2.8 %) large (640 bp) deletion, 1 (2.8 %) extended insertion (8 bp), 1 (2.8 %) insertion/duplication (505 bp). Among 12 gene conversion events, there were 7 full and 5 partial events. The tract length in the mutants with partial conversion varies from 44 to 2247 bp. According to literature data such DNA changes as gene conversion, extended deletions, and indels must be the products of homologous recombination, single-strand annealing, and non-homologous ends joining repair pathways, respectively. We propose that the initial DNA lesions for DNA changes are different types of DNA double-strand breaks (DSB): (i) complex DSBs, (ii) less complex DSBs, and (iii) simple DSBs. Comparing the spectrum of DNA changes in the <em>cn</em> gene/point mutants with that in <em>black</em> one, it is important to note that the ratio of DNA changes in various genomic regions may be different.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"903 ","pages":"Article 503857"},"PeriodicalIF":2.3,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AI/ML modeling to enhance the capability of in vitro and in vivo tests in predicting human carcinogenicity","authors":"Ani Tevosyan ,&nbsp;Hrach Yeghiazaryan ,&nbsp;Gohar Tadevosyan ,&nbsp;Lilit Apresyan ,&nbsp;Vahe Atoyan ,&nbsp;Anna Misakyan ,&nbsp;Zaven Navoyan ,&nbsp;Helga Stopper ,&nbsp;Nelly Babayan ,&nbsp;Lusine Khondkaryan","doi":"10.1016/j.mrgentox.2025.503858","DOIUrl":"10.1016/j.mrgentox.2025.503858","url":null,"abstract":"<div><div>This study aimed to develop an in silico model for predicting human carcinogenicity using advanced deep learning techniques, specifically Graph Neural Networks (GNN), through a multitask learning (MTL) approach. The MTL framework leveraged auxiliary tasks, including mutagenicity, genotoxicity, animal carcinogenicity, androgen and estrogen receptor binding, to enhance the model's predictive capabilities for the primary task of human carcinogenicity. Three distinct GNN architectures were used alongside various combinations of auxiliary tasks to evaluate the variations in performance metrics. Results demonstrated that multitask learning significantly enhances the predictive performance of GNN models compared to single-task learning for predicting human carcinogenicity. The best performed MTL model achieved an area under the curve of 0.89, along with a balanced accuracy of 82 %, and sensitivity and specificity values of 0.75 and 0.89, respectively. The developed multitask learning (MTL) models function on tasks that represent assays for identifying both genotoxic and non-genotoxic carcinogens, thereby enhancing the model's capability to predict human carcinogenic risk with greater accuracy. The advanced GNN models demonstrated effectiveness in addressing data imbalance issues frequently observed in biological datasets, mitigating the bias that typically favors one class over another. Overall, these results underscore the promise of GNN-based MTL models for reliable chemical screening and prioritization, particularly in predicting human carcinogenicity.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"903 ","pages":"Article 503858"},"PeriodicalIF":2.3,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety evaluation of ethanolic extract from aerial flowering part of spiny globe thistle (Echinops spinosus) in mice: Phytochemical screening and genotoxicity","authors":"Kawthar A. Diab ,&nbsp;Maha A. Fahmy ,&nbsp;Entessar E. Hassan ,&nbsp;Ahmed M. Nagy ,&nbsp;Ayman A. Farghaly ,&nbsp;Emad M. Hassan ,&nbsp;Enayat A. Omara","doi":"10.1016/j.mrgentox.2025.503854","DOIUrl":"10.1016/j.mrgentox.2025.503854","url":null,"abstract":"<div><div><em>Echinops spinosus</em> is widely used by the population due to its therapeutic potential; however, there is no evidence in the literature that substantiates its safety. Therefore, this study aimed to identify the chemical constituents of <em>E. spinosus</em> extract via GC/MS analysis and evaluate its cytotoxicity and genotoxicity. Male mice were orally given three doses of <em>E. spinosus</em> extract (250, 500, and 1000 mg/kg) for four weeks. Blood and tissue samples were collected after the end of treatment. GC–MS results revealed 73 compounds in the <em>E. spinosus</em> extract, including sugars, sugar alcohols, fatty acids, organic acids, amino acids, and nitrogenous compounds. <em>In vitro</em> experiments revealed that <em>E. spinosus</em> was not cytotoxic to human colon, prostate, or breast cancer cells. <em>In vivo</em> experiments showed that <em>E. spinosus</em> extract did not significantly induce chromosomal damage in the bone marrow, primary spermatocyte, or sperm morphology abnormalities at doses up to 1000 mg/kg/day. This extract also did not induce DNA damage at doses <em>≤ 500 mg/kg/day</em> in the bone marrow, spleen, testis, or spermatozoa and at 250 mg/kg/day in the liver or kidney. However, treatment with a high dose of <em>E. spinosus</em> caused significant disturbances in liver and kidney functions, oxidative stress indicators, comet tail formation, and histological architecture of the liver, kidney, and testis. In conclusion<em>, E. spinosus</em> extract is nontoxic, with an oral LD₅₀ &gt; 5000 mg/kg. The extract showed negative genotoxicity within the safety threshold of ≤ 500 mg/kg/day and positive genotoxicity at a dose of 1000 mg/kg/day.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"902 ","pages":"Article 503854"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143376923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dose-response curve for induction of unstable chromosome aberrations by 6 MV linear accelerator photons: Analysis of intra-experimental variations","authors":"Volodymyr Vinnikov ,&nbsp;Dominika Kochanova ,&nbsp;Katarína Vigašová ,&nbsp;Sachin Gulati ,&nbsp;Matúš Durdík ,&nbsp;Pavol Košík ,&nbsp;Eva Marková ,&nbsp;Lukáš Jakl ,&nbsp;Lucián Zastko ,&nbsp;Kristína Kontrišová ,&nbsp;Igor Belyaev","doi":"10.1016/j.mrgentox.2025.503849","DOIUrl":"10.1016/j.mrgentox.2025.503849","url":null,"abstract":"<div><div>Cytogenetic biodosimetry relies on dose-response curves (DRCs) for each type of radiation that can cause a radiation emergency. We have constructed a DRC based on the dicentric assay. Blood samples from four healthy volunteers were irradiated with acute 6 MV linac photons, 0.46–4.55 Gy; 0.68 and 1.37 Gy doses were used in the ‘blind’ validation study. Lymphocytes were cultured with variations in time delay in mitogenic stimulation after irradiation (2 vs. 16 h) and mitotic arrest by colchicine (3.5 vs. 16 h). Aberrations were scored in the first division metaphases, ensured by fluorescence-plus-Giemsa staining. DRCs for dicentrics and dicentrics plus centric rings were efficiently fitted using the linear-quadratic model. We show, for the first time, that neither prolonged mitotic arrest nor delayed mitogenic stimulation has any effect on DRC. However, the latter factor caused a significant increase in the yield of the second division metaphase in culture. Inter-donor differences in the DRC for aberrations were not large, but individual changes in the frequencies of second-division cells were highly variable. In the validation study, the DRC combined from all experimental series provided dose estimates that were as accurate as those, obtained using the donors’ individual or culture-type specific DRCs. The DRC coefficients in present study were slightly higher than those reported previously for linac beams and close to values for orthovoltage X-rays. Further cytogenetic studies of megavoltage radiation beams require stringent standardization of experimental conditions.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"902 ","pages":"Article 503849"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143152748","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}