Mutation research. Genetic toxicology and environmental mutagenesis最新文献

英文中文

Investigation of genetic instability in patients with Diabetes Mellitus type I, II and LADA using buccal micronucleus cytome assay 利用口腔微核细胞组测定法研究 I 型、II 型和 LADA 型糖尿病患者的遗传不稳定性

IF 2.3 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation research. Genetic toxicology and environmental mutagenesis

Pub Date : 2024-11-01 DOI: 10.1016/j.mrgentox.2024.503828

G. Parsadanyan , G. Zalinyan , R. Markosyan , M. Sarkisyan , E. Aghajanova , A. Sahakyan

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.

我们的试验性研究旨在调查 I 型、II 型和 LADA（成人潜伏性自身免疫性糖尿病，被归类为 1.5 型中间缓慢进展型糖尿病）糖尿病（DM）患者口腔黏膜脱落细胞中微核（MN）和其他核异常的频率，并使用 MN 测试将他们与亚美尼亚人口中的健康人进行比较。研究了每位参与者的基本临床和生化参数，包括血压、病程、糖化血红蛋白（HbA1c）、血糖、血浆葡萄糖、尿素、总蛋白、肌酐、总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、HOMA-IR（胰岛素抵抗）、胰岛素和甘油三酯，以及必要的人体测量、家谱和遗传数据。所有参与者都接受了可能影响 MN 水平的习惯调查，如吸烟、饮酒、吸毒、遗传性疾病和病毒感染。脱落细胞的细胞遗传学分析表明，与健康人相比，DM 患者脱落细胞中的 MN 水平高出约两到三倍。不过，只有I型DM和LADA患者的MN水平达到了统计学意义。研究人员还分析了 DM 患者鳞状上皮细胞中其他核异常的水平，发现在所有三种 DM 类型中，这些核异常的水平都显著升高，这表明它们具有细胞毒性和基因毒性作用。研究结果还显示，MN 总数、MN 细胞数、血糖浓度和糖化血红蛋白之间存在高度相关性。

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引用次数: 0

Disperse Red 1 azo dye: Consequences of low-dose/low-concentration exposures in mice and zebrafish 分散红 1 偶氮染料：小鼠和斑马鱼低剂量/低浓度接触的后果

IF 2.3 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation research. Genetic toxicology and environmental mutagenesis

Pub Date : 2024-11-01 DOI: 10.1016/j.mrgentox.2024.503830

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

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.

颜色指数分散红 1（DR1）是一种广泛用于纺织业并被排放到水生环境中的偶氮染料，在体细胞中具有遗传毒性，但人们对其对生殖系统或胚胎发育早期阶段的影响知之甚少。我们评估了雄性小鼠口服低剂量染料 14 天后精子受到的影响。测量终点包括 DNA 损伤（彗星试验）、miRNA-34c 水平以及精子数量、形态和活力。暴露会导致 miRNA-34c 水平下降。我们还研究了染料对斑马鱼胚胎和幼虫的影响，包括发育障碍、谷胱甘肽转移酶活性改变以及对活性氧和脂质过氧化水平的影响。

引用次数: 0

In vitro hepatic 3D cell models and their application in genetic toxicology: A systematic review 体外肝脏三维细胞模型及其在遗传毒理学中的应用：系统综述

IF 2.3 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation research. Genetic toxicology and environmental mutagenesis

Pub Date : 2024-11-01 DOI: 10.1016/j.mrgentox.2024.503835

Martina Štampar, Bojana Žegura

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 in vitro tests, followed by in vivo 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 in vitro 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 in vitro 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 in vitro models for the safety testing of chemicals and pharmaceuticals. 3D cell models provide physiologically relevant information and more predictive data for in vivo 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 in vitro 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.

新化学品和消费品的快速发展引起了人们对其对人类健康的潜在基因毒性影响的关注，包括 DNA 损伤导致的严重疾病。对于此类新化学品和医药产品，国际法规要求首先通过体外试验获得遗传毒性数据，然后再根据需要进行体内试验。传统上，实验动物一直被用于这一目的，但它们成本高昂，存在伦理问题，而且由于物种差异，往往不可靠。因此，人们正在迅速开发更精确的创新体外测试方法，以取代、改造和减少（3R）实验动物的使用，并提高毒理学研究与人类的相关性。其中一种创新方法是体外三维（3D）细胞模型，这种模型已被视为二维（2D）细胞培养的优越替代品，而二维（2D）细胞培养传统上被用作化学品和药品安全性测试的体外模型。三维细胞模型可提供与生理相关的信息，并为体内条件提供更具预测性的数据。在这篇综述文章中，我们全面概述了三维肝细胞模型（包括 HepG2、HepG2/C3A、HepaRG、人类原代肝细胞和 iPSC 衍生肝细胞）及其在遗传毒理学领域的应用。通过详细的文献分析，我们确定了 2007 年至 2024 年 4 月期间进行的 31 项研究，这些研究采用了各种标准方法，如彗星试验、微核试验和 γH2AX 试验，以及包括毒物基因组学在内的新方法，来评估化学品、纳米颗粒和天然毒素的细胞毒性和基因毒性活性。根据我们的搜索，我们可以得出结论：多年来，体外三维细胞模型在遗传毒性测试中的应用越来越多，三维细胞模型在遗传毒理学和风险评估中的未来应用和进一步完善具有更大的潜力。

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引用次数: 0

Bruce Nathan Ames: A scientist to remember (December 16, 1928—October 5, 2024)

IF 2.3 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation research. Genetic toxicology and environmental mutagenesis

Pub Date : 2024-11-01 DOI: 10.1016/j.mrgentox.2024.503832

David M. DeMarini

引用次数: 0

A Special Issue honoring Prof. Michael Fenech

IF 2.3 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation research. Genetic toxicology and environmental mutagenesis

Pub Date : 2024-11-01 DOI: 10.1016/j.mrgentox.2024.503834

Armen Nersesyan, Claudia Bolognesi, Stefano Bonassi, Siegfried Knasmueller

引用次数: 0

In memoriam – Professor Diana Anderson (1940–2024)

IF 2.3 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation research. Genetic toxicology and environmental mutagenesis

Pub Date : 2024-11-01 DOI: 10.1016/j.mrgentox.2024.503831

Michael Dee Waters

引用次数: 0

Genotoxicity analysis of a flame retardant, aluminum diethylphosphinate 阻燃剂二乙基膦酸铝的遗传毒性分析

IF 2.3 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation research. Genetic toxicology and environmental mutagenesis

Pub Date : 2024-11-01 DOI: 10.1016/j.mrgentox.2024.503829

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

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: Salmonella/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 Salmonella 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.

阻燃剂对防火至关重要，在全球范围内得到广泛应用，但它们被认为是 "新出现的污染物"，可能对人类和环境健康造成危害。二乙基膦酸铝（ALPI）是一种无卤阻燃剂。为了评估这种化合物的毒性，我们进行了以下检测：沙门氏菌/微粒体致突变试验；两个终点（线粒体脱氢酶活性、质膜完整性）的毒性试验；人肝癌细胞系 HepG2 的微核试验。ALPI 对沙门氏菌菌株 TA97、TA98、TA100、TA102 或 TA104 均无诱变作用。在任何测试浓度下，ALPI 都没有细胞毒性。HepG2 微核试验显示，ALPI 在 200 微克/毫升时具有遗传毒性，而在 200 微克/毫升时没有细胞毒性（细胞分裂阻滞增殖指数，CBPI）。我们的数据与阻燃剂的监管有关。

引用次数: 0

Impact of gold nanoparticle exposure on genetic material 纳米金粒子暴露对遗传物质的影响

IF 2.3 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation research. Genetic toxicology and environmental mutagenesis

Pub Date : 2024-10-05 DOI: 10.1016/j.mrgentox.2024.503827

Lucía Ramos-Pan , Assia Touzani , Natalia Fernández-Bertólez , Sónia Fraga , Blanca Laffon , Vanessa Valdiglesias

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. In vitro and in vivo 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.

以金纳米粒子（AuNP）为代表的金属纳米粒子因其独特的性能而备受关注。在纳米尺度上，金显示出卓越的物理、化学、光学和电子特性，使其成为生物成像、传感、诊断和药物输送等大量应用的理想选择。尽管金纳米粒子的应用前景广阔，但人们也开始担心金纳米粒子对人体健康的潜在不利影响。研究表明，这些纳米粒子可在重要器官中积聚，并与蛋白质和细胞结构相互作用，可能导致各种毒理学表现。由于 AuNP 的理化特性各不相同，影响其生物效应，因此要准确理解这些纳米生物相互作用变得更加复杂。本综述旨在整合目前有关 AuNP 基因毒性效应的知识，阐明影响其毒性的潜在机制和因素。本综述在 PubMed 和 Web of Science 数据库中进行了搜索。最终，32 项关注 AuNP 基因毒性效应的研究被纳入综述。体外和体内研究结果表明，AuNP 可诱发原发性 DNA 损伤、氧化性 DNA 损伤、染色体损伤、基因表达改变以及对表观遗传调控的影响。这些效应受多种因素的影响，包括纳米粒子的大小、形状和表面涂层。然而，现有文献也强调了与评估纳米材料（NM）遗传毒性相关的挑战，强调了标准化和适应性测试协议的必要性。纳米颗粒对传统毒性检测的干扰可能会导致不可靠的结果；因此，必须采用专门针对纳米材料评估的特定方法。总之，虽然 AuNP 具有创新应用的巨大潜力，但其安全性仍是一个关键问题。当务之急是继续开展研究，以阐明 AuNP 诱导遗传毒性的机制，并制定稳健的测试协议，确保在各种应用中安全有效地使用 AuNP。

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引用次数: 0

Genotoxicity in the goldfish of TiO2 nanoparticles combined with high CO2 levels 二氧化钛纳米颗粒与高浓度二氧化碳对金鱼的遗传毒性

IF 2.3 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation research. Genetic toxicology and environmental mutagenesis

Pub Date : 2024-09-28 DOI: 10.1016/j.mrgentox.2024.503826

I. Bilgiseven , N. Gülsoy

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.

二氧化钛纳米粒子具有光催化作用，可产生活性氧，对水生生物群落有害。我们研究了 nTiO2 与水中高浓度 CO2 结合产生的毒性效应。我们将金鱼暴露在与环境相关的二氧化钛浓度和二氧化碳浓度下。彗星试验结果表明，高浓度二氧化碳会增加DNA断裂，但二氧化钛浓度没有影响。微核试验显示没有明显的微核形成。鱼鳃出现了组织病理学变化，但肝脏没有。

引用次数: 0

The effect of aging on the repeated-dose liver micronucleus assay using N-nitrosodipropylamine, quinoline, and carbendazim 老化对使用 N-亚硝基二丙胺、喹啉和多菌灵进行的重复剂量肝脏微核试验的影响

IF 2.3 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation research. Genetic toxicology and environmental mutagenesis

Pub Date : 2024-09-16 DOI: 10.1016/j.mrgentox.2024.503825

Kensuke Satomoto , Moeko Aoki , Osamu Hashiguchi , Hiroshi Yamagata , Takezo Okamoto , Natsuki Konishi , Naoteru Denta , Ryoko Harada , Shuichi Hamada

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.

重复剂量肝脏微核试验（RDLMN）在研究的化学品数量和类型方面已得到充分验证。不过，目前仍不清楚老化是否会影响检测结果。OECD 测试指南 407（啮齿动物 28 天重复剂量口服毒性研究）指出，应在断奶后尽快开始给药，且无论如何应在 9 周龄前开始。因此，在考虑是否有可能将该检测方法纳入为期 4 周的重复剂量一般毒性研究时，确定开始给药时的 6 周龄和 8 周龄之间是否存在与年龄相关的差异尤为重要。我们用三种化学品评估了大鼠年龄对 RDLMN 试验的影响：N-亚硝基二丙胺、喹啉和多菌灵。前两种化学物质没有明显的年龄差异，而在多菌灵中，年龄较小的大鼠出现微核肝细胞（MNHEPs）的频率明显较高。不过，无论动物的年龄如何，这三种化学品都能检测到微核诱导。结合之前有关氯贝特和二乙基亚硝胺的报告，我们得出结论，6 至 8 周龄的动物均可用于 RDLMN 试验。

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