{"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}
Miluse Vozdova, Svatava Kubickova, Vera Kopecka, Jaroslav Sipek, Jiri Rubes
{"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, Svatava Kubickova, Vera Kopecka, Jaroslav Sipek, 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}
Andrea G. Cardozo , Daniel C. Castrogiovanni , Alejandro D. Bolzán
{"title":"Bleomycin-induced chromosomal aberrations in Epstein-Barr virus-transformed human lymphoblastoid cells","authors":"Andrea G. Cardozo , Daniel C. Castrogiovanni , 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}
{"title":"Trends in the cytogenetic and immunologic status of healthy persons; Kazakhstan, 2007–2022","authors":"Oksana Cherednichenko , Georgij Demchenko , Unzira Kapysheva , Sholpan Bakhtiyarova , Anastasiya Pilyugina , Dinara Azizbekova , Ulbosin Kozhaniyazova , Bolatbek Zhaksymov","doi":"10.1016/j.mrgentox.2024.503822","DOIUrl":"10.1016/j.mrgentox.2024.503822","url":null,"abstract":"<div><p>Environmental pollution can affect immune health and genome stability. We have studied the immunological and cytogenetic status of healthy urban (Almaty City, which has high levels of air pollution) and rural residents of southern Kazakhstan, over the past 15 years. Differences between the groups in plasma immunoglobulin levels and chromosomal aberration frequencies were noted. Over the 15-year study period, decreases of immunoglobulin levels and increases of chromosomal aberration frequencies were observed and correlated with place of residence and ecological status of the region of residence; both ecological deterioration and the coronavirus pandemic are likely to have had negative effects.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"899 ","pages":"Article 503822"},"PeriodicalIF":2.3,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1383571824000986/pdfft?md5=a3d4980c0e118c6ef193b8cd1ead6420&pid=1-s2.0-S1383571824000986-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142049691","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":"β-aminoisobutyric acid ameliorated type 1 diabetes-induced germ cell toxicity in rat: Studies on the role of oxidative stress and IGF-1/AMPK/SIRT-1 signaling pathway","authors":"Archna Panghal, Gopabandhu Jena","doi":"10.1016/j.mrgentox.2024.503820","DOIUrl":"10.1016/j.mrgentox.2024.503820","url":null,"abstract":"<div><p>Diabetes mellitus is known as the “epidemic of the century” due to its global prevalence. Several pre-clinical and clinical studies have shown that male germ cell toxicity is one of the major consequences of diabetes mellitus. Although β-aminoisobutyric acid (BAIBA) has been shown to be advantageous in the diabetic nephropathy and cardiomyopathy, its specific role in the diabetes-induced testicular toxicity remains unknown. In this study, an attempt was made to elucidate the molecular mechanisms of BAIBA-mediated germ cell protection in diabetic rats. Adult male Sprague-dawley rats were subjected to either no treatment (control) or BAIBA (100 mg/kg; BAIBA control) or Streptozotocin (50 mg/kg; diabetic control) or low (25 mg/kg), medium (50 mg/kg) and high (100 mg/kg) doses of BAIBA in diabetic conditions. Significant alterations in sperm related parameters, oxidative stress and apoptotic biomarkers, pancreatic and testicular histology, DNA damage and changes in expression of proteins in testes were found in the diabetic rats. 100 mg/kg of BAIBA significantly reduced the elevated blood glucose levels (<em>P</em> ≤ 0.05), increased body weight (<em>P</em> ≤ 0.01 in the 4th week), lowered malondialdehyde (<em>P</em> ≤ 0.05) and nitrite levels (<em>P</em> ≤ 0.01), elevated testosterone (<em>P</em> ≤ 0.05) and FSH levels (<em>P</em> ≤ 0.05), increased sperm count and motility (<em>P</em> ≤ 0.01), decreased testicular DNA damage (P ≤ 0.001), improved histological features of pancreas and testes, decreased TUNEL positive cells (<em>P</em> ≤ 0.01), decreased RAGE (<em>P</em> ≤ 0.01) and Bax (<em>P</em> ≤ 0.05) expressions and increased SIRT1 (<em>P</em> ≤ 0.05) and Atg 12 (<em>P</em> ≤ 0.05) expressions in the testes. 50 mg/kg of BAIBA partially restored the above-mentioned parameters whereas 25 mg/kg of BAIBA was found to be insignificant in counteracting the toxicity. It is interesting to note that BAIBA protects male germ cell damage in diabetic rats by regulating the IGF-1/AMPK/SIRT-1 signaling pathway.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"899 ","pages":"Article 503820"},"PeriodicalIF":2.3,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142049690","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":"Development of a genotoxicity/carcinogenicity assessment method by DNA adductome analysis","authors":"Kohei Watanabe , Masami Komiya , Asuka Obikane , Tsubasa Miyazaki , Kousuke Ishino , Keita Ikegami , Hiroki Hashizume , Yukako Ishitsuka , Takashi Fukui , Min Gi , Shugo Suzuki , Hideki Wanibuchi , Yukari Totsuka","doi":"10.1016/j.mrgentox.2024.503821","DOIUrl":"10.1016/j.mrgentox.2024.503821","url":null,"abstract":"<div><p>Safety evaluation is essential for the development of chemical substances. Since <em>in vivo</em> safety evaluation tests, such as carcinogenesis tests, require long-term observation using large numbers of experimental animals, it is necessary to develop alternative methods that can predict genotoxicity/carcinogenicity in the short term, taking into account the 3Rs (replacement, reduction, and refinement). We established a prediction model of the hepatotoxicity of chemicals using a DNA adductome, which is a comprehensive analysis of DNA adducts that may be used as an indicator of DNA damage in the liver. An adductome was generated with LC-high-resolution accurate mass spectrometer (HRAM) on liver of rats exposed to various chemicals for 24 h, based on two independent experimental protocols. The resulting adductome dataset obtained from each independent experiment (experiments 1 and 2) and integrated dataset were analyzed by linear discriminant analysis (LDA) and found to correctly classify the chemicals into the following four categories: non-genotoxic/non-hepatocarcinogens (−/−), genotoxic/non-hepatocarcinogens (+/−), non-genotoxic/hepatocarcinogens (−/+), and genotoxic/hepatocarcinogens (+/+), based on their genotoxicity/carcinogenicity properties. A prototype model for predicting the genotoxicity/carcinogenicity of the chemicals was established using machine learning methods (using random forest algorithm). When the prototype genotoxicity/carcinogenicity prediction model was used to make predictions for experiments 1 and 2 as well as the integrated dataset, the correct response rates were 89 % (genotoxicity), 94 % (carcinogenicity) and 87 % (genotoxicity/carcinogenicity) for experiment 1, 47 % (genotoxicity), 62 % (carcinogenicity) and 42 % (genotoxicity/carcinogenicity) for experiment 2, and 52 % (genotoxicity), 62 % (carcinogenicity), and 48 % (genotoxicity/carcinogenicity) for the integrated dataset. To improve the accuracy of the toxicity prediction model, the toxicity label was reconstructed as follows; Pattern 1: when +/+ and −/− chemicals were used from the toxicity labels +/+, +/−, −/+ and −/−; and Pattern 2: when +/+, +/−, and −/+ other than −/− were replaced with the label \"Others\". As a result, chemicals with only +/+ and −/− toxicity labels were used and the correct response rates were approximately 100 % for the measured data in experiment 1, 53 %–66 % for the data in experiment 2, and 59–73 % for the integrated data, all of which were 10 %–30 % higher compared with the data before the label change. In contrast, when the toxicity labels were replaced with −/− and “Others”, they reached nearly 100 % in the measured data from experiment 1, 65 %–75 % in the data from experiment 2, and 70 %–78 % in the integrated data, all of which were 10 %–50 % higher compared with the data before the label change.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"899 ","pages":"Article 503821"},"PeriodicalIF":2.3,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142044333","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}