Mutation research. Genetic toxicology and environmental mutagenesis最新文献

{"title":"Persons chronically exposed to low doses of ionizing radiation: A cytogenetic dosimetry study","authors":"Oksana Cherednichenko,&nbsp;Anastassiya Pilyugina,&nbsp;Serikbai Nuraliev,&nbsp;Dinara Azizbekova","doi":"10.1016/j.mrgentox.2024.503728","DOIUrl":"10.1016/j.mrgentox.2024.503728","url":null,"abstract":"<div><p>The dosimetry and control of exposure for individuals chronically exposed to ionizing radiation are important and complex issues. Assessment may be optimized by evaluating individual adaptation and radiosensitivity, but it is not possible for a single model to account for all relevant parameters. Our goal was to develop approaches for the calculation of doses for persons chronically exposed to ionizing radiation, taking their radiosensitivities into consideration. On the basis of ex vivo radiation of blood samples, dose-effect models were constructed for dose ranges 0.01–2.0 and 0.01–0.4 Gy, using different cytogenetic criteria. The frequencies of \"dicentric chromosomes and rings\" at low doses are too low to have predictive value. The different responses of subjects to radiation made it possible to categorize them according to their radiosensitivities and to generate separate dose-effect curves for radiosensitive, average, and radioresistant individuals, reducing the amount of error in retrospective dosimetry.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"894 ","pages":"Article 503728"},"PeriodicalIF":1.9,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1383571824000044/pdfft?md5=86b0eba3a7285cd53331811ad0c7c585&pid=1-s2.0-S1383571824000044-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139496502","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 buccal micronucleus cytome assay: New horizons for its implementation in human studies","authors":"Michael Fenech ,&nbsp;Siegfried Knasmueller ,&nbsp;Armen Nersesyan ,&nbsp;Claudia Bolognesi ,&nbsp;Georg Wultsch ,&nbsp;Christian Schunck ,&nbsp;Emanuela Volpi ,&nbsp;Stefano Bonassi","doi":"10.1016/j.mrgentox.2023.503724","DOIUrl":"10.1016/j.mrgentox.2023.503724","url":null,"abstract":"<div><p><span>In this report we provide a summary of the presentations and discussion of the latest knowledge regarding the buccal micronucleus (MN) cytome assay. This information was presented at the HUMN workshop held in Malaga, Spain, in connection with the 2023 European, Environmental Mutagenesis and Genomics conference. The presentations covered the most salient topics relevant to the buccal MN cytome assay including (i) the biology of the </span>buccal mucosa, (ii) its application in human studies relating to DNA damage caused by environmental exposure to genotoxins, (iii) the association of buccal MN with cancer and a wide range of reproductive, metabolic, immunological, neurodegenerative and other age-related diseases, (iv) the impact of nutrition and lifestyle on buccal MN cytome assay biomarkers; (v) its potential for application to studies of DNA damage in children and obesity, and (vi) the growing prospects of enhancing the clinical utility by automated scoring of the buccal MN cytome assay biomarkers by image recognition software developed using artificial intelligence. The most important knowledge gap is the need of prospective studies to test whether the buccal MN cytome assay biomarkers predict health and disease.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"894 ","pages":"Article 503724"},"PeriodicalIF":1.9,"publicationDate":"2024-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139376015","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 assessment and communication of genotoxicity test results: moving beyond binary","authors":"Takashi Omori ,&nbsp;Makoto Hayashi","doi":"10.1016/j.mrgentox.2023.503722","DOIUrl":"10.1016/j.mrgentox.2023.503722","url":null,"abstract":"<div><p>Potential genotoxicity is one of the essential considerations in the safety assessment of chemicals to which humans may be exposed. Several endpoints are used to evaluate genotoxicity, but, in each case, a binary assessment (negative/positive) is demanded by regulators. The use of binary assessment has rarely been questioned, although we have pointed out some questions and difficulties with regard to the statistical methods used and the evaluation of biological significance, both of which inform the calls of negative/ positive. Here, we discuss these issues further, focusing on ambiguity and uncertainty in the binary paradigm, and we seek a new direction for genotoxicity assessment. To this end, we need to understand, acknowledge, and accept these ambiguities and study-related uncertainties and then to consider new strategies for safety assessment. We also discuss the communication of ambiguity and uncertainty in risk communication.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"893 ","pages":"Article 503722"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139035359","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":"Occupational exposure to radiation among health workers: Genome integrity and predictors of exposure","authors":"Hayal Çobanoğlu,&nbsp;Akın Çayır","doi":"10.1016/j.mrgentox.2024.503726","DOIUrl":"10.1016/j.mrgentox.2024.503726","url":null,"abstract":"<div><p><span>The current study aimed to investigate genomic instabilities<span> in healthcare workers who may experience varying levels of radiation exposure through various radiological procedures. It also sought to determine if factors related to the work environment and dosimeter<span> reading could effectively explain the observed genomic instabilities. Utilizing the cytokinesis-block micronucleus assay (CBMN) on </span></span></span>peripheral blood lymphocytes<span>, we assessed a spectrum of genomic aberrations, including nucleoplasmic bridge (NPB), nuclear budding (NBUD), micronucleus (MN) formation, and total DNA damage (TDD). The study uncovered a statistically significant increase in the occurrence of distinct DNA anomalies among radiology workers (with a significance level of P &lt; 0.0001 for all measurements). Notably, parameters such as total working hours, average work duration, and time spent in projection radiography exhibited significant correlations with MN and TDD levels in these workers. The dosimeter readings demonstrated a positive correlation with the frequency of NPB and NBUD, indicating a substantial association between radiation exposure and these two genomic anomalies. Our multivariable models identified the time spent in projection radiography as a promising parameter for explaining the overall genomic instability observed in these professionals. Thus, while dosimeters alone may not fully explain elevated total DNA damage, intrinsic work environment factors hold potential in indicating exposure levels for these individuals, providing a complementary approach to monitoring.</span></p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"893 ","pages":"Article 503726"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139422527","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 and the stability of N-nitrosomorpholine activity following UVA irradiation","authors":"Haruna Mochizuki ,&nbsp;Yukari Nagazawa ,&nbsp;Sakae Arimoto-Kobayashi","doi":"10.1016/j.mrgentox.2023.503721","DOIUrl":"10.1016/j.mrgentox.2023.503721","url":null,"abstract":"<div><p>This study investigated <em>N</em><span><span><span>-nitrosomorpholine (NMOR) genotoxicity following UVA irradiation without </span>metabolic activation. Following UVA irradiation, the photo treated NMOR (irradiated NMOR) was directly mutagenic, without UVA or metabolic activation, in the </span>Ames test. The activity was relatively stable, and approximately 79% of the activity remained after 10 days of storage at 37 °C, 4 °C, or −20 °C. Micronuclei (MN) formation was observed in HaCaT cells after treatment with irradiated NMOR without metabolic activation. The action spectrum of MN formation in response to NMOR irradiation followed the NMOR absorption curve. </span><em>In vivo</em><span>, MN formation was observed in the peripheral blood reticulocytes<span> of mice injected with irradiated NMOR under the inhibition of cytochrome P450-mediated metabolism of NMOR. Volatile NMOR may attach to environmental materials and be irradiated with environmental UVA light. Photoactivated NMOR-attached air pollutants could float in the air and fall onto the human body, leading to genotoxicity induced by the irradiated NMOR.</span></span></p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"893 ","pages":"Article 503721"},"PeriodicalIF":1.9,"publicationDate":"2023-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138507365","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":"Mutagenicity assessment of two potential impurities in preparations of 5-amino-2,4,6 triiodoisophthalic acid, a key intermediate in the synthesis of the iodinated contrast agent iopamidol","authors":"Silvia Rossi ,&nbsp;Simona Bussi ,&nbsp;Roberta Bonafè ,&nbsp;Carola Incardona ,&nbsp;Emanuela Vurro ,&nbsp;Massimo Visigalli ,&nbsp;Federica Buonsanti ,&nbsp;Roberta Fretta","doi":"10.1016/j.mrgentox.2023.503720","DOIUrl":"https://doi.org/10.1016/j.mrgentox.2023.503720","url":null,"abstract":"<div><p>5-Aminoisophthalic acid and 5-nitroisophthalic acid (5-NIPA) are potential impurities in preparations of 5-amino-2,4,6-triiodoisophthalic acid, which is a key intermediate in the synthesis of the iodinated contrast agent iopamidol. We have studied their mutagenicity <em>in silico</em> (quantitative structure-activity relationships, QSAR) and by the bacterial reverse mutation assay (Ames test). First, the compounds were screened with the tools Derek Nexus™ and Leadscope®. Both compounds were flagged as potentially mutagenic (class 3 under ICH M7). However, contrary to the <em>in silico</em> prediction, neither chemical was mutagenic in the Ames test (plate incorporation method) with or without S9 metabolic activation.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"893 ","pages":"Article 503720"},"PeriodicalIF":1.9,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1383571823001389/pdfft?md5=685f5f9623b3c76ab72a40ecd22f5300&pid=1-s2.0-S1383571823001389-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138475185","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":"Oxidative DNA damage: Induction by fructose, in vitro, and its enhancement by hydrogen peroxide","authors":"Kaoru Midorikawa ,&nbsp;Kokoro Kobayashi ,&nbsp;Shinya Kato ,&nbsp;Shosuke Kawanishi ,&nbsp;Hatasu Kobayashi ,&nbsp;Shinji Oikawa ,&nbsp;Mariko Murata","doi":"10.1016/j.mrgentox.2023.503719","DOIUrl":"https://doi.org/10.1016/j.mrgentox.2023.503719","url":null,"abstract":"<div><p>Sucrose and high-fructose corn syrup comprise nearly equal amounts of glucose and fructose. With the use of high-fructose corn syrup in the food industry, consumption of fructose, which may be a tumor promoter, has increased dramatically. We examined fructose-induced oxidative DNA damage in the presence of Cu(II), with or without the addition of H₂O₂. With isolated DNA, fructose induced Cu(II)-mediated DNA damage, including formation of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), to a greater extent than did glucose, and H₂O₂ enhanced the damage. In cultured human cells, 8-oxodG formation increased significantly following treatment with fructose and the H₂O₂-generating enzyme glucose oxidase. Fructose may play an important role in oxidative DNA damage, suggesting a possible mechanism for involvement of fructose in carcinogenesis.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"893 ","pages":"Article 503719"},"PeriodicalIF":1.9,"publicationDate":"2023-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1383571823001377/pdfft?md5=366d6e8e7fd41824a49d9c535ffb2158&pid=1-s2.0-S1383571823001377-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138489967","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":"Assessment of the performance of the Ames MPF™ assay: A multicenter collaborative study with six coded chemicals","authors":"Dimitrios Spiliotopoulos ,&nbsp;Cécile Koelbert ,&nbsp;Marc Audebert ,&nbsp;Ilona Barisch ,&nbsp;Deborah Bellet ,&nbsp;Mathilde Constans ,&nbsp;Andreas Czich ,&nbsp;Francis Finot ,&nbsp;Véronique Gervais ,&nbsp;Laure Khoury ,&nbsp;Christian Kirchnawy ,&nbsp;Sachiko Kitamoto ,&nbsp;Audrey Le Tesson ,&nbsp;Laure Malesic ,&nbsp;Ryoko Matsuyama ,&nbsp;Elisa Mayrhofer ,&nbsp;Isabelle Mouche ,&nbsp;Birgit Preikschat ,&nbsp;Lukas Prielinger ,&nbsp;Bernhard Rainer ,&nbsp;Kerstin Wäse","doi":"10.1016/j.mrgentox.2023.503718","DOIUrl":"https://doi.org/10.1016/j.mrgentox.2023.503718","url":null,"abstract":"<div><p><span><span>The Ames MPF™ is a miniaturized, microplate fluctuation format of the </span>Ames test<span>. It is a standardized, commercially available product which can be used to assess mutagenicity in </span></span><em>Salmonella</em> and <em>E. coli</em><span> strains in 384-well plates using a color change-based readout. Several peer-reviewed comparisons of the Ames MPF™ to the Ames test in Petri dishes confirmed its suitability to evaluate the mutagenic potential of a variety of test items. An international multicenter study involving seven laboratories tested six coded chemicals with this assay using five bacterial strains, as recommended by the OECD test guideline 471. The data generated by the participating laboratories was in excellent agreement (93%), and the similarity of their dose response curves, as analyzed with sophisticated statistical approaches further confirmed the suitability of the Ames MPF™ assay as an alternative to the Ames test on agar plates, but with advantages with respect to significantly reduced amount of test substance and S9 requirements, speed, hands-on time and, potentially automation.</span></p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"893 ","pages":"Article 503718"},"PeriodicalIF":1.9,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138490976","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":"Mutagenic effects of a commercial glyphosate-based herbicide formulation on the soil filamentous fungus Aspergillus nidulans depending on the mode of exposure","authors":"Nathalie Oestreicher ,&nbsp;Jean-Paul Bourdineaud ,&nbsp;Christian Vélot","doi":"10.1016/j.mrgentox.2023.503708","DOIUrl":"https://doi.org/10.1016/j.mrgentox.2023.503708","url":null,"abstract":"<div><p>Glyphosate-based herbicides (GBH) are the most used pesticides worldwide. This widespread dissemination raises the question of non-target effects on a wide range of organisms, including soil micro-organisms. Despite a large body of scientific studies reporting the harmful effects of GBHs, the health and environmental safety of glyphosate and its commercial formulations remains controversial. In particular, contradictory results have been obtained on the possible genotoxicity of these herbicides depending on the organisms or biological systems tested, the modes and durations of exposure and the sensitivity of the detection technique used. We previously showed that the well-characterized soil filamentous fungus <em>Aspergillus nidulans</em> was highly affected by a commercial GBH formulation containing 450 g/L of glyphosate (R450), even when used at doses far below the agricultural application rate. In the present study, we analysed the possible mutagenicity of R450 in <em>A. nidulans</em> by screening for specific mutants after different modes of exposure to the herbicide. R450 was found to exert a mutagenic effect only after repeated exposure during growth on agar-medium, and depending on the metabolic status of the tested strain. The nature of some mutants and their ability to tolerate the herbicide better than did the wild-type strain suggested that their emergence may reflect an adaptive response of the fungus to offset the herbicide effects. The use of a non-selective molecular approach, the quantitative random amplified polymorphic DNA (RAPD-qPCR), showed that R450 could also exert a mutagenic effect after a one-shot overnight exposure during growth in liquid culture. However, this effect was subtle and no longer detectable when the fungus had previously been repeatedly exposed to the herbicide on a solid medium. This indicated an elevation of the sensitivity threshold of <em>A. nidulans</em> to the R450 mutagenicity, and thus confirmed the adaptive capacity of the fungus to the herbicide.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"892 ","pages":"Article 503708"},"PeriodicalIF":1.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92039589","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":"Saxagliptin, a selective dipeptidyl peptidase-4 inhibitor, alleviates somatic cell aneugenicity and clastogenicity in diabetic mice","authors":"Sabry M. Attia,&nbsp;Sheikh F. Ahmad,&nbsp;Ahmed Nadeem,&nbsp;Mohamed S.M. Attia,&nbsp;Mushtaq A. Ansari,&nbsp;Abdelkader E. Ashour,&nbsp;Norah A. Albekairi,&nbsp;Mohammed A. Al-Hamamah,&nbsp;Ali A. Alshamrani,&nbsp;Saleh A. Bakheet","doi":"10.1016/j.mrgentox.2023.503707","DOIUrl":"https://doi.org/10.1016/j.mrgentox.2023.503707","url":null,"abstract":"<div><p>Diabetes-related complications are becoming increasingly common as the global prevalence of diabetes increases. Diabetes is also linked to a high risk of developing cancer. This raises the question of whether cancer vulnerability is caused by diabetes itself or the use of antidiabetic drugs. Chromosomal instability, a source of genetic modification involving either an altered chromosomal number or structure, is a hallmark of cancer. Saxagliptin has been approved by the FDA for diabetes treatment. However, the detailed <em>in vivo</em> effects of prolonged saxagliptin treatment on chromosomal instability have not yet been reported. In this study, streptozotocin was used to induce diabetes in mice, and both diabetic and non-diabetic mice received saxagliptin for five weeks. Fluorescence <em>in situ</em> hybridization was conducted in combination with a bone marrow micronucleus test for measuring chromosomal instability. Our results indicated that saxagliptin is neither mutagenic nor cytotoxic, under the given treatment regimen. Diabetic mice had a much higher incidence of micronuclei formation, and a centromeric DNA probe was present inside the majority of the induced micronuclei, indicating that most of these were caused by chromosome nondisjunction. Conversely, diabetic mice treated with saxagliptin exhibited a significant decrease in micronuclei induction, which were centromeric-positive and centromeric-negative. Diabetes also causes significant biochemical changes indicative of oxidative stress, such as increased lipid peroxidation and decreased reduced/oxidized glutathione ratio, which was reversed by saxagliptin administration. Overall, saxagliptin, the non-mutagenic antidiabetic drug, maintains chromosomal integrity in diabetes and reduces micronuclei formation by restoring redox imbalance, further indicating its usefulness in diabetic patients.</p></div>","PeriodicalId":18799,"journal":{"name":"Mutation research. Genetic toxicology and environmental mutagenesis","volume":"892 ","pages":"Article 503707"},"PeriodicalIF":1.9,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49849065","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}