Mutation research. Genetic toxicology and environmental mutagenesis最新文献

{"title":"In vitro hepatic 3D cell models and their application in genetic toxicology: A systematic review","authors":"Martina Štampar,&nbsp;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":"Bruce Nathan Ames: A scientist to remember (December 16, 1928—October 5, 2024)","authors":"David M. DeMarini","doi":"10.1016/j.mrgentox.2024.503832","DOIUrl":"10.1016/j.mrgentox.2024.503832","url":null,"abstract":"","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"900 ","pages":"Article 503832"},"PeriodicalIF":2.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746226","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 Special Issue honoring Prof. Michael Fenech","authors":"Armen Nersesyan,&nbsp;Claudia Bolognesi,&nbsp;Stefano Bonassi,&nbsp;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 ,&nbsp;A.S. Fernandes ,&nbsp;I. Felzenszwalb ,&nbsp;C.F. Araujo-Lima ,&nbsp;D.P. Oliveira ,&nbsp;D.J. Dorta ,&nbsp;C.F. Sampaio ,&nbsp;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 ,&nbsp;Assia Touzani ,&nbsp;Natalia Fernández-Bertólez ,&nbsp;Sónia Fraga ,&nbsp;Blanca Laffon ,&nbsp;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 ,&nbsp;N. Gülsoy","doi":"10.1016/j.mrgentox.2024.503826","DOIUrl":"10.1016/j.mrgentox.2024.503826","url":null,"abstract":"<div><div>TiO₂ nanoparticles are photocatalytic, generate reactive oxygen, and can be harmful to aquatic biota. We have studied the toxic effects of nTiO₂ combined with high CO₂ levels in water. We exposed goldfish to environmentally relevant concentrations of nTiO₂ and CO₂ levels. Comet assay results showed that DNA breaks increased at high CO₂ concentration, but no effect of nTiO₂ 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 ,&nbsp;Moeko Aoki ,&nbsp;Osamu Hashiguchi ,&nbsp;Hiroshi Yamagata ,&nbsp;Takezo Okamoto ,&nbsp;Natsuki Konishi ,&nbsp;Naoteru Denta ,&nbsp;Ryoko Harada ,&nbsp;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}

{"title":"Human sperm mitochondrial DNA copy numbers and deletion rates: Comparing persons living in two urban industrial agglomerations differing in sources of air pollution","authors":"Miluse Vozdova,&nbsp;Svatava Kubickova,&nbsp;Vera Kopecka,&nbsp;Jaroslav Sipek,&nbsp;Jiri Rubes","doi":"10.1016/j.mrgentox.2024.503824","DOIUrl":"10.1016/j.mrgentox.2024.503824","url":null,"abstract":"<div><p>Persons living in industrial environments are exposed to levels of air pollution that can affect their health and fertility. The Czech capital city, Prague, and the Ostrava industrial agglomeration differ in their major sources of air pollution. In Prague, heavy traffic produces high levels of nitrogen oxides throughout the year. In the Ostrava region, an iron industry and local heating are sources of particulate matter (PM) and benzo[<em>a</em>]pyrene (B[<em>a</em>]P), especially in the winter. We evaluated the effects of air pollution on human sperm mitochondrial DNA (mtDNA). Using real-time PCR, we analysed sperm mtDNA copy number and deletion rate in Prague city policemen in two seasons (spring and autumn) and compared the results with those from Ostrava. In Prague, the sperm mtDNA deletion rate was significantly higher in autumn than in spring, which is the opposite of the results from Ostrava. The sperm mtDNA copy number did not show any seasonal differences in either of the cities; it was correlated negatively with sperm concentration, motility, and viability, and with sperm chromatin integrity (assessed with the Sperm Chromatin Structure Assay). The comparison between the two cities showed that the sperm mtDNA deletion rate in spring and the sperm mtDNA copy number in autumn were significantly lower in Prague vs. Ostrava. Our study supports the hypothesis that sperm mtDNA deletion rate is affected by the composition of air pollution. Sperm mtDNA abundance is closely associated with chromatin damage and standard semen characteristics.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"899 ","pages":"Article 503824"},"PeriodicalIF":2.3,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142162418","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":"Bleomycin-induced chromosomal aberrations in Epstein-Barr virus-transformed human lymphoblastoid cells","authors":"Andrea G. Cardozo ,&nbsp;Daniel C. Castrogiovanni ,&nbsp;Alejandro D. Bolzán","doi":"10.1016/j.mrgentox.2024.503823","DOIUrl":"10.1016/j.mrgentox.2024.503823","url":null,"abstract":"<div><p>We have evaluated the induction of complete (i.e., without open ends) and incomplete (i.e., with non-rejoined or open ends) chromosomal aberrations by the radiomimetic antibiotic bleomycin (BLM) in human lymphoblastoid cells immortalized with the Epstein-Barr virus (EBV). An EBV-induced lymphoblastoid cell line (T-37) was exposed to BLM (10–200 µg/mL) for 2 h at 37ºC, and chromosomal aberrations were analyzed 24 h after treatment, using PNA-FISH with pan-telomeric and pan-centromeric probes. Both complete (multicentrics, rings, compound acentric fragments, and interstitial deletions) and incomplete (incomplete chromosomes or IC, and terminal acentric fragments or TAF) chromosomal aberrations increased significantly in BLM-exposed cells, although the concentration-response relationship was non-linear. Of the acentric fragments (ace) induced by BLM, 40 % were compound fragments (CF, ace +/+). TAF (ace, +/-) and interstitial fragments (IAF, ace -/-) were induced at similar frequencies (30 %). 230 ICE were induced by BLM, of which 52 % were IC and 48 % TAF. The average ratio between total incomplete chromosome elements (ICE) and multicentrics was 1.52. These findings suggest that human lymphoblastoid cells exhibit less repair capacity than human lymphocytes, with respect to BLM-induced ICE, and that chromosomal incompleteness is a common event following exposure of these cells to BLM.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"899 ","pages":"Article 503823"},"PeriodicalIF":2.3,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096276","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}