G. Parsadanyan , G. Zalinyan , R. Markosyan , M. Sarkisyan , E. Aghajanova , A. Sahakyan
{"title":"Investigation of genetic instability in patients with Diabetes Mellitus type I, II and LADA using buccal micronucleus cytome assay","authors":"G. Parsadanyan , G. Zalinyan , R. Markosyan , M. Sarkisyan , E. Aghajanova , A. Sahakyan","doi":"10.1016/j.mrgentox.2024.503828","DOIUrl":"10.1016/j.mrgentox.2024.503828","url":null,"abstract":"<div><div>The aim of our pilot study was to investigate the frequency of micronuclei (MN) and other nuclear anomalies in exfoliated cells of the oral mucosa in patients with type I, II, and LADA (Latent Autoimmune Diabetes in Adults, classified as type 1.5 intermediate, slowly progressing diabetes) types of diabetes mellitus (DM) and compare them with healthy individuals of the Armenian population using the MN test. For each participant essential clinical and biochemical parameters were studied, including blood pressure, duration of illness, glycosylated hemoglobin (HbA1c), blood glucose, plasma glucose, urea, total protein, creatinine, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, HOMA-IR (insulin resistance), insulin, and triglycerides, as well as necessary anthropometric, genealogical, and genetic data. All participants were surveyed regarding habits that might affect MN levels, such as smoking, alcohol consumption, drug use, hereditary diseases, and viral infections. Cytogenetic analyses of exfoliated cells showed that the level of MN in exfoliated cells of DM patients was elevated approximately two to three times compared to healthy individuals. However, statistical significance was only reached in type I DM and LADA patients. The levels of other nuclear anomalies in the squamous epithelial cells of DM patients were also analyzed, and a significant increase in their levels was observed in all three DM types, indicating cytotoxic and genotoxic effects. The results of this study also revealed a high correlation between the total number of MN, cells with MN, blood glucose concentration, and glycosylated hemoglobin.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"900 ","pages":"Article 503828"},"PeriodicalIF":2.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142554162","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}
Fábio Henrique Fernandes , Flávia Renata Abe , Tamara Barbosa Gomes , Cibele Borges dos Santos , Wilma De Grava Kempinas , Bianca Arruda Leite , Danielle Palma de Oliveira , Daisy Maria Fávero Salvadori
{"title":"Disperse Red 1 azo dye: Consequences of low-dose/low-concentration exposures in mice and zebrafish","authors":"Fábio Henrique Fernandes , Flávia Renata Abe , Tamara Barbosa Gomes , Cibele Borges dos Santos , Wilma De Grava Kempinas , Bianca Arruda Leite , Danielle Palma de Oliveira , Daisy Maria Fávero Salvadori","doi":"10.1016/j.mrgentox.2024.503830","DOIUrl":"10.1016/j.mrgentox.2024.503830","url":null,"abstract":"<div><div>Color Index Disperse Red 1 (DR1), an azo dye widely used in the textile industry and released into aquatic environments, is genotoxic in somatic cells, but little is known concerning its effects on the reproductive system or the early stages of embryonic development. We have assessed the effects on the spermatozoa of male mice following oral exposure to the dye, at low doses, for 14 days. Measured endpoints were DNA damage (comet assay), miRNA-34c levels, and sperm number, morphology, and motility. Exposure caused decreased miRNA-34c levels. We have also examined dye effects on zebrafish embryos and larvae, which included developmental impairment, altered glutathione transferase activity, and effects on reactive oxygen species and lipid peroxidation levels.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"900 ","pages":"Article 503830"},"PeriodicalIF":2.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142652770","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":"In vitro hepatic 3D cell models and their application in genetic toxicology: A systematic review","authors":"Martina Štampar, Bojana Žegura","doi":"10.1016/j.mrgentox.2024.503835","DOIUrl":"10.1016/j.mrgentox.2024.503835","url":null,"abstract":"<div><div>The rapid development of new chemicals and consumer products has raised concerns about their potential genotoxic effects on human health, including DNA damage leading to serious diseases. For such new chemicals and pharmaceutical products, international regulations require genotoxicity data, initially obtained through <em>in vitro</em> tests, followed by <em>in vivo</em> experiments, if needed. Traditionally, laboratory animals have been used for this purpose, however, they are costly, ethically problematic, and often unreliable due to species differences. Therefore, innovative more accurate <em>in vitro</em> testing approaches are rapidly being developed to replace, refine and reduce (3R) the use of animals for experimental purposes and to improve the relevance for humans in toxicology studies. One of such innovative approaches are <em>in vitro</em> three-dimensional (3D) cell models, which are already being highlighted as superior alternatives to the two-dimensional (2D) cell cultures that are traditionally used as <em>in vitro</em> models for the safety testing of chemicals and pharmaceuticals. 3D cell models provide physiologically relevant information and more predictive data for <em>in vivo</em> conditions. In the review article, we provide a comprehensive overview of 3D hepatic cell models, including HepG2, HepG2/C3A, HepaRG, human primary hepatocytes, and iPSC-derived hepatocytes, and their application in the field of genotoxicology. Through a detailed literature analysis, we identified 31 studies conducted between 2007 and April 2024 that used a variety of standard methods, such as the comet assay, the micronucleus assay, and the γH2AX assay, as well as new methodological approaches, including toxicogenomics, to assess the cytotoxic and genotoxic activity of chemicals, nanoparticles and natural toxins. Based on our search, we can conclude that the use of <em>in vitro</em> 3D cell models for genotoxicity testing has been increasing over the years and that 3D cell models have an even greater potential for future implementation and further refinement in genetic toxicology and risk assessment.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"900 ","pages":"Article 503835"},"PeriodicalIF":2.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142652699","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":"A Special Issue honoring Prof. Michael Fenech","authors":"Armen Nersesyan, Claudia Bolognesi, Stefano Bonassi, Siegfried Knasmueller","doi":"10.1016/j.mrgentox.2024.503834","DOIUrl":"10.1016/j.mrgentox.2024.503834","url":null,"abstract":"","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"900 ","pages":"Article 503834"},"PeriodicalIF":2.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745678","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":"In memoriam – Professor Diana Anderson (1940–2024)","authors":"Michael Dee Waters","doi":"10.1016/j.mrgentox.2024.503831","DOIUrl":"10.1016/j.mrgentox.2024.503831","url":null,"abstract":"","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"900 ","pages":"Article 503831"},"PeriodicalIF":2.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745684","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":"Genotoxicity analysis of a flame retardant, aluminum diethylphosphinate","authors":"T.O.L. Leoncio , A.S. Fernandes , I. Felzenszwalb , C.F. Araujo-Lima , D.P. Oliveira , D.J. Dorta , C.F. Sampaio , E.R.A. Ferraz","doi":"10.1016/j.mrgentox.2024.503829","DOIUrl":"10.1016/j.mrgentox.2024.503829","url":null,"abstract":"<div><div>Flame retardants, crucial for fire prevention, are used worldwide, but they are considered to be ‘emerging contaminants’ and may pose risks to human and environmental health. Aluminum diethyl phosphinate (ALPI) is a halogen-free flame retardant. To evaluate the toxicity of this compound, the following assays were performed: <em>Salmonella</em>/microsome mutagenicity assay; toxicity assays with two endpoints (mitochondrial dehydrogenase activity, plasma membrane integrity); micronucleus assay with human hepatoma cell line HepG2. ALPI was not mutagenic in <em>Salmonella</em> strains TA97, TA98, TA100, TA102, or TA104. ALPI was not cytotoxic at any concentration tested. The HepG2 micronucleus assay showed genotoxicity of ALPI at 200 µg/mL and no cytotoxicity (cytokinesis-block proliferation index, CBPI). Our data are relevant to the regulation of flame retardants.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"900 ","pages":"Article 503829"},"PeriodicalIF":2.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142593131","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":"Impact of gold nanoparticle exposure on genetic material","authors":"Lucía Ramos-Pan , Assia Touzani , Natalia Fernández-Bertólez , Sónia Fraga , Blanca Laffon , Vanessa Valdiglesias","doi":"10.1016/j.mrgentox.2024.503827","DOIUrl":"10.1016/j.mrgentox.2024.503827","url":null,"abstract":"<div><div>Metal nanoparticles, with gold nanoparticles (AuNP) at the forefront, have gained immense attention due to their unique properties. At the nanoscale, gold exhibits remarkable physical, chemical, optical, and electronic features, making it ideal for a plethora of applications, including bioimaging, sensing, diagnostics, and drug delivery. Despite their promising utility, concerns have arisen regarding the potential adverse effects of AuNP on human health. Research has indicated that these nanoparticles can accumulate in vital organs and interact with proteins and cellular structures, potentially leading to diverse toxicological manifestations. The precise understanding of these nano-bio interactions is further complicated by the varied physicochemical properties of AuNP that influence their biological effects. This review aims to consolidate the current knowledge on the genotoxic effects of AuNP, shedding light on the underlying mechanisms and factors affecting their toxicity. The search was conducted in PubMed and Web of Science databases. Eventually, 32 studies focusing on the genotoxic effects of AuNP were included in the review. <em>In vitro</em> and <em>in vivo</em> findings revealed that AuNP can induce primary DNA damage, oxidative DNA damage, chromosomal damage, alterations in gene expression, and effects on epigenetic regulation. These effects were found to be influenced by various factors, including nanoparticle size, shape, and surface coating. However, the existing literature also highlights the challenges associated with assessing the genotoxicity of nanomaterials (NM), emphasizing the need for standardized and adapted testing protocols. The interference of nanoparticles with conventional toxicity assays may lead to unreliable results; thus, specific methodologies tailored for NM evaluation must be implemented. In conclusion, while AuNP hold tremendous potential for innovative applications, their safety profile remains a critical concern. Continued research is imperative to elucidate the mechanisms of AuNP induced genotoxicity and develop robust testing protocols, ensuring their safe and effective use in diverse applications.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"900 ","pages":"Article 503827"},"PeriodicalIF":2.3,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142424932","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":"Genotoxicity in the goldfish of TiO2 nanoparticles combined with high CO2 levels","authors":"I. Bilgiseven , N. Gülsoy","doi":"10.1016/j.mrgentox.2024.503826","DOIUrl":"10.1016/j.mrgentox.2024.503826","url":null,"abstract":"<div><div>TiO<sub>2</sub> nanoparticles are photocatalytic, generate reactive oxygen, and can be harmful to aquatic biota. We have studied the toxic effects of nTiO<sub>2</sub> combined with high CO<sub>2</sub> levels in water. We exposed goldfish to environmentally relevant concentrations of nTiO<sub>2</sub> and CO<sub>2</sub> levels. Comet assay results showed that DNA breaks increased at high CO<sub>2</sub> concentration, but no effect of nTiO<sub>2</sub> concentrations was seen. Micronucleus assays showed no significant micronucleus formation. Histopathological alterations were seen in the gills but not in the liver.</div></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"900 ","pages":"Article 503826"},"PeriodicalIF":2.3,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142424931","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":"The effect of aging on the repeated-dose liver micronucleus assay using N-nitrosodipropylamine, quinoline, and carbendazim","authors":"Kensuke Satomoto , Moeko Aoki , Osamu Hashiguchi , Hiroshi Yamagata , Takezo Okamoto , Natsuki Konishi , Naoteru Denta , Ryoko Harada , Shuichi Hamada","doi":"10.1016/j.mrgentox.2024.503825","DOIUrl":"10.1016/j.mrgentox.2024.503825","url":null,"abstract":"<div><p>The repeated dose liver micronucleus (RDLMN) assay has been sufficiently validated in terms of the numbers and types of chemicals studied. However, it remains unclear whether aging affects assay results. The OECD Test Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents) indicates that dosing should begin as soon as feasible after weaning and in any event before 9 weeks of age. Therefore, it is particularly important to determine whether there are age-related differences between 6 and 8 weeks of age at the start of dosing when considering the possibility of integrating this assay into a 4-week repeated dose general toxicity study. We evaluated the impact of the rats’ age on the RDLMN assay with three chemicals: N-nitrosodipropylamine, quinoline, and carbendazim. There were no significant age-related differences for the first two chemicals, whereas a markedly higher frequency of micronucleated hepatocytes (MNHEPs) was observed in younger rats for carbendazim. However, regardless of the age of animals, micronucleus induction was detected in all three chemicals. Combined with the previous reports on clofibrate and diethylnitrosamine, we concluded that animals of any age from 6 to 8 weeks could be used in the RDLMN assay.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"899 ","pages":"Article 503825"},"PeriodicalIF":2.3,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239925","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}