Mutation research. Genetic toxicology and environmental mutagenesis最新文献_第6页

A comparative analysis of select P450 enzymes in uninduced and PB/BNF-induced hamster and rat liver S9 P450酶在未诱导和PB/ bnf诱导的仓鼠和大鼠肝脏中的比较分析

IF 2.3 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation research. Genetic toxicology and environmental mutagenesis

Pub Date : 2025-02-01 DOI: 10.1016/j.mrgentox.2025.503855

Kristie Evans , Slaydon Boitnotte , Errol Zeiger , Jennifer Cheung , Anthony Lynch

The assessment of potentially carcinogenic N-nitrosamine impurities in drugs has become crucial for the pharmaceutical industry to ensure public safety. The in vitro Ames test, which uses rat or hamster liver S9 for metabolic activation, is an important component of regulatory test batteries for assessing mutagenicity and has been the traditional method for assessing the potential mutagenicity of chemicals, including N-nitrosamines. This test, however, has shown inconsistencies with some N-nitrosamines, raising concerns about the liver S9's ability to activate N-nitrosamines to their proximate mutagens. Assays from Vivid® CYP450 Screening Kits and the 7-benzyloxyquinoline assay were used to measure substrate activities of P450 enzymes involved in N-nitrosamine metabolism in rat and hamster liver S9. Both uninduced and induced rat and hamster liver S9 preparations were used. The results provide a comparative assessment of the metabolic competency of the rodent S9s to metabolize N-nitrosamines to their mutagenic forms. Hamster S9 consistently showed increased CYP activity compared to rat S9 under the same conditions. Induced rat S9 also displayed relatively high conversion levels, with the greatest increase in 7-benzyloxyquinoline conversion (CYP3A-like activity) over uninduced (15.7-fold). The highest increase observed with induced hamster S9 was for CYP2A6-like activity which was induced over 7.8-fold and was ∼60-fold higher in induced hamster S9 compared to induced rat S9. These results demonstrate that both rat and hamster S9 contain relevant P450 enzyme activities for N-nitrosamine bioactivation, but hamster S9 is recommended for nitrosamine in vitro tests due to its overall higher P450 activity levels.

药物中潜在致癌性n -亚硝胺杂质的评估已成为制药行业确保公共安全的关键。体外Ames试验利用大鼠或仓鼠肝脏S9进行代谢激活，是评估突变性的调控试验电池的重要组成部分，是评估包括n -亚硝胺在内的化学物质潜在突变性的传统方法。然而，该试验显示与某些n -亚硝胺不一致，这引起了人们对肝脏S9激活n -亚硝胺对其近似诱变剂的能力的担忧。采用Vivid®CYP450筛选试剂盒和7-苯氧喹啉法测定大鼠和仓鼠肝脏S9中参与n -亚硝胺代谢的P450酶的底物活性。采用未诱导和诱导的大鼠和仓鼠肝脏S9制剂。这些结果提供了啮齿动物S9s代谢n -亚硝胺到其致突变形式的代谢能力的比较评估。在相同条件下，仓鼠S9与大鼠S9相比，CYP活性持续增加。诱导大鼠S9也显示出相对较高的转化水平，7-苯氧喹啉转化（cyp3a样活性）比未诱导的增加最多（15.7倍）。与诱导的大鼠S9相比，诱导的仓鼠S9中cyp2a6样活性的增加幅度最大，达到7.8倍以上，而诱导的仓鼠S9中cyp2a6样活性的增加幅度为60倍。这些结果表明，大鼠和仓鼠S9都含有与n -亚硝胺生物活性相关的P450酶活性，但仓鼠S9因其整体P450活性水平较高而被推荐用于亚硝胺体外试验。

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引用次数: 0

Fibroblast-based radiosensitivity assays as a clinically valuable tool for (severe) combined immunodeficiency syndromes 基于成纤维细胞的放射敏感性测定作为（严重）联合免疫缺陷综合征的临床有价值的工具

IF 2.3 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation research. Genetic toxicology and environmental mutagenesis

Pub Date : 2025-02-01 DOI: 10.1016/j.mrgentox.2025.503852

Elien Beyls , Somara De Beul , Victoria Bordon , Alina Ferster , Filomeen Haerynck , Anne Vral , Ans Baeyens

Genetic defects in one of the DNA double strand break (DSB) repair proteins lead to distinct human syndromes with severe clinical manifestations, including impaired neurological and immunological development, cancer proneness and sensitivity to ionizing radiation. Since diagnostic and therapeutic procedures frequently use DNA damaging agents, identification of radiosensitive individuals is imperative to optimize patient management. However, patients with a (severe) combined immunodeficiency (S)CID are often ineligible for lymphocyte-based radiosensitivity testing. Therefore, this study investigated the suitability of two fibroblast-based assays as alternative methods. DSB repair was evaluated following X-ray irradiation by an optimized cytokinesis-block micronucleus (MN) assay and the γH2AX focus test in fibroblasts from patients with a confirmed or suspected diagnosis of radiosensitive (S)CID. Using both assays, patients with a defect in Artemis were identified as radiosensitive while those with a RAG1/2 deficiency were not considered as radiosensitive. Although MN scoring was not feasible in irradiated fibroblasts deficient in XLF, LIG4 or NBS1, radiosensitivity could be readily demonstrated through impaired DNA DSB repair kinetics with the γH2AX focus assay in fibroblasts deficient in XLF or LIG4, but not in those deficient in NBS1. While both ATM defective fibroblasts clearly showed increased radiation-induced MN yields, one of the two fibroblast cell lines could not be identified as radiosensitive based on residual γH2AX focus levels. This study suggests that combining the fibroblast MN assay and γH2AX focus test can effectively exclude in vitro radiosensitivity in patients with a suspicion of radiosensitive (S)CID, particularly when lymphocyte-based radiosensitivity testing is not feasible.

DNA双链断裂（DSB）修复蛋白之一的遗传缺陷导致具有严重临床表现的不同人类综合征，包括神经和免疫发育受损、癌症易感性和对电离辐射的敏感性。由于诊断和治疗过程经常使用DNA损伤剂，识别放射敏感个体是优化患者管理的必要条件。然而，患有（严重）联合免疫缺陷(S)CID的患者通常不适合进行基于淋巴细胞的放射敏感性试验。因此，本研究探讨了两种基于成纤维细胞的检测方法作为替代方法的适用性。通过优化的细胞动力学阻滞微核（MN）测定和γ - h2ax聚焦试验，对确诊或疑似放射敏感(S)CID患者的成纤维细胞进行x射线照射后DSB修复评估。使用这两种检测方法，Artemis缺陷的患者被确定为放射敏感，而RAG1/2缺陷的患者不被认为是放射敏感。虽然在XLF、LIG4或NBS1缺乏的受辐射成纤维细胞中MN评分是不可行的，但在XLF或LIG4缺乏的成纤维细胞中，通过γ - h2ax聚焦试验损伤的DNA DSB修复动力学可以很容易地证明放射敏感性，而在NBS1缺乏的成纤维细胞中则不能。虽然两种ATM缺陷成纤维细胞都明显显示出辐射诱导的MN产量增加，但根据残余γ - h2ax聚焦水平，两种成纤维细胞中的一种不能被确定为辐射敏感。本研究表明，结合成纤维细胞MN试验和γH2AX焦点试验可以有效地排除疑似放射敏感(S)CID患者的体外放射敏感性，特别是在淋巴细胞放射敏感性试验不可行的情况下。

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引用次数: 0

Low dose X-radiation induced DNA damage and its association with Glandular dose in women undergoing mammography 接受乳房x光检查的妇女低剂量x射线引起的DNA损伤及其与腺体剂量的关系

IF 2.3 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation research. Genetic toxicology and environmental mutagenesis

Pub Date : 2025-02-01 DOI: 10.1016/j.mrgentox.2025.503856

Jivantika Daya Thejas , Sanjna Vinod , Divya K. Mohan , Bhawna Dev , Jai Prakash Srinivasan , Venkateswarlu Raavi , Venkatachalam Perumal

Mammography is a widespread X-ray-based tool used for screening as well as early diagnosis of certain diseases related to breast tissue. However, the use of X-rays in mammography raised concern as a series of low-dose radiation exposures received during this procedure might increase health risks similar to high doses of acute exposure. To understand the effects of low-dose X-irradiation, blood samples were drawn from healthy volunteers (n = 5), X-irradiated in vitro with a dose similar to that obtained during mammography (2.5–3 mGy/plane), and also from women undergoing digital breast tomosynthesis imaging (before and after 1–2 h) (n = 18) were used as models. The level of induced DNA damage was determined using γ-H2AX foci and micronucleus (MN) formation in blood lymphocytes. In the in vitro irradiated samples, the mean γ-H2AX foci frequency in unirradiated control was 0.12 ± 0.03, and in irradiated samples was 0.25 ± 0.02 (p < 0.0001). A similar increase in mean γ-H2AX foci frequency of 0.13 ± 0.01 and 0.21 ± 0.05 was observed before and after mammography imaging respectively (p < 0.0001). A similar trend was observed for in vitro MN where the frequency was 0.0008 ± 0.0008 in unirradiated control and 0.0046 ± 0.0018 in irradiated samples (p < 0.01). Whereas, a heterogeneous increase in MN frequency was observed in women who underwent mammography (p < 0.001). Pearson correlation revealed a strong correlation between Average Glandular Dose (AGD) and γ-H2AX frequency (r²=0.7820) and a weak correlation between AGD and MN frequency (r²=0.0008). The present study suggests that the low doses of radiation from mammography imaging have the potential to induce early DNA damage and residual DNA damage observed until 72 h post-exposure; it might result in an increased risk for stochastic health effects during their lifetime.

乳房x光摄影是一种广泛使用的基于x光的工具，用于筛查和早期诊断与乳腺组织有关的某些疾病。然而，在乳房x光检查中使用x射线引起了关注，因为在此过程中接受的一系列低剂量辐射暴露可能增加与高剂量急性暴露相似的健康风险。为了了解低剂量x射线照射的影响，健康志愿者的血液样本（n = 5），体外x射线照射剂量与乳房x光检查（2.5-3 mGy/平面）相似，以及接受数字乳房断层合成成像（1-2小时前后）的妇女的血液样本（n = 18）被用作模型。采用γ-H2AX聚焦法和血淋巴细胞微核（MN）形成法测定DNA损伤水平。在体外辐照样品中，未辐照对照的γ-H2AX平均焦频率为0.12 ± 0.03，辐照样品的平均焦频率为0.25 ± 0.02 （p <； 0.0001）。乳腺x线造影前后γ-H2AX平均聚焦频率分别升高0.13 ± 0.01和0.21 ± 0.05 （p <； 0.0001）。在体外MN中也观察到类似的趋势，未辐照对照组的频率为0.0008 ± 0.0008，辐照样品的频率为0.0046 ± 0.0018 （p <； 0.01）。然而，在接受乳房x光检查的女性中，观察到MN频率的异质性增加（p <； 0.001）。Pearson相关分析显示，平均腺剂量（AGD）与γ-H2AX频率相关性强（r2=0.7820），与MN频率相关性弱（r2=0.0008）。目前的研究表明，乳房x线摄影成像的低剂量辐射有可能诱发早期DNA损伤和暴露后72 h观察到的残留DNA损伤；这可能会导致他们一生中受到随机健康影响的风险增加。

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引用次数: 0

Micronuclei as genotoxicity endpoint applied in the co-culture of two mammalian cell lines 将微核作为遗传毒性终点应用于两种哺乳动物细胞系的共培养。

IF 2.3 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation research. Genetic toxicology and environmental mutagenesis

Pub Date : 2025-01-01 DOI: 10.1016/j.mrgentox.2024.503839

Naji Said Aboud Hadi , Helga Stopper

There has been a shift from traditional animal models towards alternative methods. While 2D cell culture has a decade long tradition, more advances methods like 3D cultures, organoids, and co-culture techniques, which better mimic in vivo conditions, are not yet well established in every research area. Genotoxicity assessment is an integral part of toxicological testing or regulatory approval of pharmaceuticals and chemicals. The micronucleus assay is now a standard method in this context. In this systematic literature review, we aim to describe the state of the art of the application of co-cultures of two mammalian cell lines for micronucleus assessment. We summarized the cell types used, methods for co-culture, disease models and agents, as well as the application of additional genotoxicity endpoints and viability tests. Airway system cells were the most frequent, followed by macrophage-like cells, liver cells, and various others. Co-culture techniques involve either direct physical contact or separation by porous membranes. Within a limited number of investigations using other genotoxicity assays like the comet and γH2AX assays in parallel, the micronucleus assay performed well. Overall, the micronucleus test demonstrating its suitability in disease models and for a more complex substance testing beyond simple 2D cultures, encouraging a more widespread use in co-culture systems in the future.

人们已经从传统的动物模型转向了替代方法。虽然2D细胞培养已经有十年的传统，但3D培养、类器官和共培养技术等更先进的方法，更好地模拟体内条件，尚未在每个研究领域都得到很好的建立。遗传毒性评估是药物和化学品的毒理学测试或监管批准的一个组成部分。微核化验现在是这方面的标准方法。在这个系统的文献综述中，我们的目的是描述两种哺乳动物细胞系共培养用于微核评估的应用现状。我们总结了使用的细胞类型，共培养方法，疾病模型和药物，以及其他遗传毒性终点和活力测试的应用。气道系统细胞是最常见的，其次是巨噬细胞样细胞、肝细胞和其他各种细胞。共培养技术包括直接物理接触或通过多孔膜分离。在使用其他遗传毒性测定方法（如comet和γH2AX测定）同时进行的有限数量的调查中，微核测定方法表现良好。总的来说，微核试验证明了它在疾病模型中的适用性，以及在简单的二维培养之外的更复杂的物质检测中，鼓励在未来的共培养系统中更广泛地使用。

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引用次数: 0

Cytotoxicity and genotoxicity of zinc oxide nanoparticles in human peripheral blood mononuclear cells 氧化锌纳米颗粒在人类外周血单核细胞中的细胞毒性和遗传毒性。

IF 2.3 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation research. Genetic toxicology and environmental mutagenesis

Pub Date : 2025-01-01 DOI: 10.1016/j.mrgentox.2024.503838

Jovanna Vanessa Ramos Angulo , Juliana Fernández Valenzuela , Sofía Isabel Freire-Bernal , Victoria Eugenia Niño-Castaño , Jorge Enrique Rodríguez Paez , Rosa Amalia Dueñas-Cuellar

Zinc oxide nanoparticles (ZnO-NPs) are of interest in biomedical applications, environmental remediation, and agriculture. ZnO-NPs inhibit the growth of phytopathogenic fungi and bacteria. We have evaluated their effects on mitochondrial function and the induction of membrane damage, apoptosis, and DNA damage in human peripheral blood mononuclear cells (PBMC) in vitro. ZnO-NPs caused significant reduction in cell viability and LDH release, indicating damage to cell membranes. Late apoptosis was significant and necrosis was significant at higher concentrations tested. ZnO-NPs did not induce micronucleus formation.

氧化锌纳米颗粒（ZnO-NPs）在生物医学、环境修复和农业等领域具有广泛的应用前景。ZnO-NPs抑制植物病原真菌和细菌的生长。我们在体外评估了它们对人外周血单核细胞（PBMC）线粒体功能和诱导膜损伤、细胞凋亡和DNA损伤的影响。ZnO-NPs导致细胞活力和LDH释放显著降低，表明细胞膜受到损伤。高浓度时，细胞晚期凋亡显著，坏死显著。ZnO-NPs不诱导微核形成。

引用次数: 0

Cytogenetic markers in newborns of mothers with comorbidities 有合并症母亲的新生儿细胞遗传学标记。

IF 2.3 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation research. Genetic toxicology and environmental mutagenesis

Pub Date : 2025-01-01 DOI: 10.1016/j.mrgentox.2024.503840

Aline C.B. Pinho , Ana Beatriz M Baston , Rita de Cássia F B Fontes , Raquel A. Santos , Marisa A.A. Brunherotti

We have studied the presence and frequency of micronuclei in exfoliated oral mucosa cells of full-term newborns and their association with maternal prenatal factors. We report an analytical, observational, cross-sectional, prospective study that includes 97 preterm infants (<37 weeks), 37 newborns from mothers with comorbidities, and 60 newborns from mothers without comorbidities, in a tertiary public hospital. Oral mucosa cells were collected within 24 h after birth. The frequency of cells with micronuclei and karyolytic cells was significantly higher in the group whose mothers had some form of comorbidity. Mothers with comorbidities had a shorter gestational age; the number of cells with micronuclei was higher in mothers with preterm premature rupture of membranes; and there were fewer karyolytic cells.

我们研究了足月新生儿脱落口腔黏膜细胞中微核的存在和频率及其与母体产前因素的关系。我们报告了一项分析性、观察性、横断面性、前瞻性研究，其中包括97名早产儿(

引用次数: 0

The transgenic MutaMouse hepatocyte mutation assay in vitro: Mutagenicity and mutation spectra of six substances with different mutagenic mechanisms 转基因MutaMouse肝细胞体外突变实验：六种不同致突变机制物质的致突变性和突变谱。

IF 2.3 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation research. Genetic toxicology and environmental mutagenesis

Pub Date : 2025-01-01 DOI: 10.1016/j.mrgentox.2024.503836

Alina Göpfert , David M. Schuster , Claudia Rülker , Michael Eichenlaub , Bogdan Tokovenko , Martina Dammann , Dorothee Funk-Weyer , Naveed Honarvar , Robert Landsiedel

Mutagenicity testing is a component of the hazard assessment of industrial chemicals, biocides, and pesticides. Mutations induced by test substances can be detected by in vitro and in vivo methods that have been adopted as OECD Test Guidelines. One of these in vivo methods is the Transgenic Rodent Assay (TGRA), OECD test guideline no. 488. An analogous in vitro TGRA has been described, but experience with this test method is limited. In this study, six in vivo TGRA positive mutagens were tested in the in vitro TGRA based on primary MutaMouse hepatocytes. In addition to the functional read-out of the lacZ reporter gene, induced mutations were analysed by next-generation sequencing (NGS). Five of the six in vivo TGRA positive mutagens (N-ethyl-N-nitrosourea (ENU), ethyl methanesulfonate (EMS), mitomycin C (MMC), benzo[a]pyrene (B[a]P), and azathioprine (AZA), but not cyproterone acetate) mutated the lacZ gene in vitro. NGS identified mutations which matched the mutagenic mechanisms described in the literature. The alkylating agent ENU induced a greater proportion of A:T to T:A transversions than did the other alkylating agent, EMS, whereas EMS increased smaller deletions (1–4 bp). G:C to T:A transversions accounted for the majority of mutations identified after treatments with MMC and B[a]P, both of which form monoadducts at the guanine N2 position. AZA induced mainly G:C to A:T transitions, explained by the structural similarity of one of its metabolites to guanine. An increased proportion of mid-size changes (0.3–2.5 kb) was detected only for the crosslinking mutagen MMC. The in vitro TGRA based on primary MutaMouse hepatocytes is a promising in vitro assay for the assessment of mutation induction, reflecting many aspects of the corresponding in vivo TGRA and allowing for mutation spectra analysis to evaluate the induced mutations.

致突变性测试是工业化学品、杀菌剂和杀虫剂危害评估的一个组成部分。由试验物质引起的突变可以通过经合组织试验指南采用的体内和体外方法进行检测。这些体内方法之一是转基因啮齿动物试验（TGRA），经合组织测试指南编号。488. 类似的体外TGRA已被描述，但这种测试方法的经验是有限的。在本研究中，6种体内TGRA阳性诱变剂在体外基于原代MutaMouse肝细胞的TGRA中进行了测试。除了lacZ报告基因的功能读出外，还通过下一代测序（NGS）分析了诱导突变。6种体内TGRA阳性诱变剂（n -乙基-n -亚硝基脲（ENU）、甲磺酸乙酯（EMS）、丝裂霉素C （MMC）、苯并[a]芘（B[a]P）和硫唑嘌呤（AZA））中有5种在体外使lacZ基因发生突变，但乙酸环丙孕酮未发生突变。NGS鉴定出与文献中描述的致突变机制相匹配的突变。烷基化剂ENU诱导的a:T到T: a平移比例高于其他烷基化剂EMS，而EMS增加了较小的缺失（1-4 bp）。在MMC和B[A]P处理后发现的突变中，G:C到T:A的倒置占了大部分，这两种突变都在鸟嘌呤N2位置形成单加合物。AZA主要诱导G:C到A:T的转变，这是因为它的一种代谢物与鸟嘌呤的结构相似。仅在交联诱变原MMC中检测到中等大小变化（0.3-2.5 kb）的比例增加。基于原代MutaMouse肝细胞的体外TGRA是一种很有前途的体外突变诱导评估方法，它反映了体内相应TGRA的许多方面，并允许突变谱分析来评估诱导突变。

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引用次数: 0

In silico and in vitro assessments of the mutagenicity of the azilsartan photoproduct 对阿齐沙坦光产物诱变性的硅学和体外评估。

IF 2.3 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation research. Genetic toxicology and environmental mutagenesis

Pub Date : 2025-01-01 DOI: 10.1016/j.mrgentox.2024.503841

Takahiro Yoshikawa , Naoto Hayashi , Masayuki Yokota

Photodegradation of azilsartan yields a phenanthridine derivative (APP). We suspected that APP could be a DNA-reactive substance, since many phenanthridine derivatives are mutagenic. In silico quantitative structure-activity relationship analysis indicated potential mutagenicity of APP, due to DNA reactivity at the 6-aminophenanthridine moiety. However, APP was not mutagenic in the Ames test. Density functional theory (DFT) calculations showed that APP cannot intercalate into DNA, due to its nonplanar structure, resulting from steric hindrance of its phenanthridine and benzimidazole moieties.

阿齐沙坦的光降解产生菲苯胺衍生物（APP）。我们怀疑APP可能是一种dna反应性物质，因为许多菲苯胺衍生物具有诱变性。硅定量构效关系分析表明，由于DNA在6-氨基苯胺部分的反应性，APP具有潜在的致突变性。然而，APP在Ames试验中不具有诱变性。密度泛函理论（DFT）计算表明，APP由于其非平面结构而无法插入DNA中，这是由其菲并啶和苯并咪唑部分的位阻造成的。

引用次数: 0

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