genotoxic

遗传毒性
  • 文章类型: Journal Article
    毒理学研究对于研究各种物质的遗传毒性作用很重要。洋葱可以用作测试模型。本文总结了该A.cepa测试模型的范围和应用。为此,在《科学直接报》上进行了最新(2023年4月)文献检索,PubMed,和WebofScience数据库,以查找使用A.cepa作为测试模型进行研究的已发表证据。在3,748项研究中,74符合纳入标准。结果表明,使用A.cepa测试模型对测量植物提取物的毒理学潜力做出了很大贡献,证明该测试作为毒性作用的有效生物指示剂的功效。此外,27项研究使用了多个测试系统来验证提取物和馏分的毒理学潜力。研究表明,A.cepa模型有可能取代其他利用动物和细胞培养的测试系统,除了具有低成本等其他优点外,易于执行,和观察染色体的良好条件。总之,可以认为A.cepa试验是粗提物毒理学研究中潜在的生物监测系统之一。
    Toxicological studies are important to investigate the genotoxic effects of various substances. Allium cepa can be used as test model for this purpose. This review summarizes the scope and applications for this A. cepa test model. For this, an up-to-date (April 2023) literature search was made in the Science Direct, PubMed, and Web of Science databases to find published evidence on studies performed using A. cepa as a test model. Out of 3,748 studies, 74 fit the inclusion criteria. The results showed that the use of the test model A. cepa contributed considerably to measuring the toxicological potential of plant extracts, proving the efficacy of the test as a potent bioindicator of toxic effects. In addition, 27 studies used more than one test system to verify the toxicological potential of extracts and fractions. Studies have shown that the A. cepa model has the potential to replace other test systems that make use of animals and cell cultures, besides having other advantages such as low cost, ease of execution, and good conditions for the observation of chromosomes. In conclusion, the A. cepa test can be considered one of the potential biomonitoring systems in toxicological studies of crude extracts.
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  • 文章类型: Journal Article
    皮肤是人体最大的器官,也是唯一与太阳紫外线辐射(UVR)接触的器官。UVA(320-400nm)是UV相关皮肤损伤的重要原因。UVA光谱占到达地球表面的太阳紫外线能量的95%以上,导致皮肤光老化的大部分可见迹象。许多消费品也会排放UVA,包括指甲烘干机。有零星的报道表明,这些单位可能有助于皮肤癌的发病率。最近发现指甲干燥机照射的哺乳动物皮肤细胞会产生与UVA暴露一致的突变特征,从而支持了这一观点。考虑到在指甲处理期间皮肤暴露于相对低水平的UVA,该报告令人惊讶。在这项研究中,我们调查了仅在低水平的UVA暴露后,发射UVA的设备如何引起细胞毒性/遗传毒性影响。我们的数据表明,单位中UVA的水平高度可变且取决于位置。我们证实了以前的报道,即使用长时间的暴露方案可能会导致显着的DNA损伤。还确定了UV诱导的DNA损伤仅与UVA流利度水平部分相关。在调查中,我们发现该装置在使用时内部温度迅速升高。将人细胞暴露于这些升高的温度与UVA协同作用以放大UV照射的细胞毒性和遗传毒性影响。
    The skin is the largest organ in the body and the only one to come into contact with solar UV radiation (UVR). UVA (320-400 nm) is a significant contributor to UV-related skin damage. The UVA spectrum makes up over 95% of solar-UV energy reaching the earth\'s surface causing the majority of the visible signs of skin photoaging. Many consumer products also emit UVA, including nail dryers. There have been sporadic reports suggesting that these units may be contributing to skin cancer incidence. This notion was recently bolstered by a finding that nail dryer-irradiated mammalian skin cells develop a mutational signature consistent with UVA exposure. This report was surprising considering the comparatively low level of UVA to which the skin is exposed during nail treatments. In this research, we investigated how UVA-emitting devices caused cytotoxic/genotoxic impact after only low levels of UVA exposure. Our data showed that levels of UVA in the unit are highly variable and location dependent. We confirm previous reports that using prolonged exposure protocols could induce significant levels of DNA damage. It was also determined that UV-induced DNA damage only partially correlated with the level of UVA fluency. On investigation, we found that the unit had a rapid increase in internal temperature when in use. Exposing human cells to these elevated temperatures acted synergistically with UVA to magnify the cytotoxic and genotoxic impact of UV irradiation.
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  • 文章类型: Editorial
    暂无摘要。
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  • 文章类型: Journal Article
    花果和酚类化合物的精油含量,根,和Heracleumpastinacifolium亚种的地上部分。通过GC/MS和LC/MS方法分析血管,分别。抗糖尿病,抗胆碱酯酶,和抗氧化活性的花果,根,地上部分甲醇提取物进行了评估。Apiole(35.0%),肉豆蔻碱(72.2%),和肉豆蔻碱(15.1%)被发现是水果-花混合物的主要化合物,根,空中部分精油,分别。发现橙皮苷在地上部分和花果提取物中含量最高,分别为8904.2621ng/mL和11558.3634ng/mL,分别。果花提取物对α-葡萄糖苷酶的活性最高(24%)。根提取物对AChE酶表现出最高的活性(18%)。花果混合甲醇提取物对ABTS·+和DPPH·具有较高的%抑制值。花果混合甲醇提取物富含总酚,总单宁,和蛋白质含量。根据艾姆斯/沙门氏菌的结果,所有提取物都被确定为遗传上安全的,大肠杆菌WP2和洋葱测定。
    Essential oil content of and phenolic compounds flower-fruit, root, and aerial parts of Heracleum pastinacifolium subsp. incanum were analysed by GC/MS and LC/MS methods, respectively. Antidiabetic, anticholinesterase, and antioxidant activities of flower-fruit, root, aerial parts methanol extracts were evaluated. Apiole (35.0%), myristicine (72.2%), and myristicine (15.1%) were found as major compounds of fruit-flower mixture, root, aerial part essential oils, respectively. Hesperidin was found the highest amount in aerial part and flower-fruit extracts with 8904.2621 ng/mL and 11558.3634 ng/mL values, respectively. Fruit-flower extract showed the highest activity against α-glucosidase (24%). Root extract demonstrating the highest activity (18%) against AChE enzyme. Flowers-fruits mixture methanol extract had a higher % inhibition value on ABTS·+ and DPPH•. Flowers-fruits mixture methanol extract was rich in total phenol, total tannin, and protein content. All the extracts were determined as genetoxically safe according to the results of Ames/Salmonella, Escherichia coli WP2 and Allium cepa assays.
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  • 文章类型: Journal Article
    癌症是一种由细胞周期调节中断引起的疾病,导致细胞的异常和无控制的增殖。药用植物富含各种生物活性植物化学物质或营养化合物。目的是确定Macarangapeltata叶的乙醇提取物对人口腔癌细胞系的细胞毒性和遗传毒性作用。研究环境是分子和应用科学研究中心,Azeezia牙科科学与研究学院。研究设计是体外比较研究。将Macarangapeltata的阴影干叶进行索氏提取,制备乙醇提取物。通过(3-(4,5-二甲基噻唑-2基)-2,5-二苯基四唑溴化物)MTT测定法评估对人口腔癌细胞系的体外细胞毒性作用,并通过彗星试验评估遗传毒性作用。未处理的细胞系用作对照,5-氟尿嘧啶用作阳性对照。所有实验一式三份进行,结果表示为平均值+/-SE。进行单因素方差分析和Dunnet检验来分析数据。与对照组相比,***P<0.001。Macarangapeltata的乙醇提取物对口腔癌细胞表现出细胞毒性(LC50:40.193089μg/ml)。细胞死亡的浓度依赖性增加,在100μg/ml时,提取物最有效,导致50%的活力抑制。与5-氟尿嘧啶和未经处理的口腔癌细胞系相比,彗星测定法显示出显着的遗传毒性作用。对Macarangapeltata叶的乙醇提取物进行MTT测定并使用KB细胞系进行彗星。该研究得出结论,该提取物对产生细胞毒性和遗传毒性的KB细胞系的抗癌活性产生了有希望的结果。
    Cancer is a disease resulting from the disruption of cell cycle regulation, leading to the abnormal and unchecked proliferation of cells. Medicinal plants are rich in various bioactive phytochemicals or nutritional compounds. The aim is to determine the cytotoxic and genotoxic effects of ethanolic extracts of Macaranga peltata leaves on human oral cancer cell lines. The study setting was centre for Research on Molecular and Applied Sciences, Azeezia College of Dental Sciences and Research. The study design is a Comparative In Vitro study. Shade dried leaves of Macaranga peltata were subjected to Soxhlet extraction, and ethanolic extract was prepared. In vitro cytotoxic effects on human oral cancer cell lines were evaluated by (3-(4,5-dimethyl thiazole-2yl)-2,5-diphenyl tetrazolium bromide) MTT assay, and genotoxic effect was evaluated by comet assay. Untreated cell lines were used as control, and 5-fluorouracil was used as positive control. All experiments were performed in triplicates, and results were represented as Mean+/- SE. One-way ANOVA and Dunnet test were performed to analyze data. ***P < 0.001 compared with the control group. The ethanolic extract of Macaranga peltata exhibited cytotoxicity against oral cancer cells (LC50: 40.193089 μg/ml). There was a concentration-dependent increase in cell death, and at 100 μg/ml, the extract was most effective, causing 50% inhibition of viability. The comet assay showed significant genotoxic effects compared with 5-fluorouracil and untreated oral cancer cell lines. The ethanolic extract of Macaranga peltata leaves was subjected to MTT assay and comet using KB cell lines. The study concludes that the extract gave promising result for the anticancer activity on the KB cell lines producing cytotoxicity and genotoxicity.
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  • 文章类型: Journal Article
    <b>背景和目的:</b>γ射线辐射诱导遗传毒性,以核外体的形成为特征,并在细胞分裂的后期阶段留下,通常被称为微核(MN)。本工作旨在监测辐射能量中心工人淋巴细胞中作为遗传毒性剂的电离辐射暴露。<b>材料与方法:</b>采用淋巴细胞胞质分裂阻滞微核试验,分析核分裂指数(NDI)的相关性,年龄,血型和微核(MN)的数量。从肝素管中收集20名志愿者的血液样本,暴露于2Gy伽马射线,体外培养<i>/i>。<b>结果:</b>A血型与A血型的微核数有显著差异,B和AB。γ辐射后,辐射能源中心工作人员淋巴细胞的核分裂指数(NDI)值很显着(1.74±0.1),但仍在正常范围内。MN频率和NDI值与年龄无关,但是MN频率与血型有关。<b>结论:</b>γ辐射没有诱导细胞抑制作用,但证明对辐射能量中心工作人员的淋巴细胞具有遗传毒性。值得注意的是,A型血对伽马射线的敏感性更高。
    <b>Background and Objective:</b> Gamma irradiation induces genotoxicity, characterized by the formation of extra-nuclear bodies and left behind during the anaphase stage of cell division, often referred to as a micronucleus (MN). The present work aims to monitor exposure to ionizing radiation as a genotoxic agent in the lymphocytes of workers at radiation energy centers. <b>Materials and Methods:</b> The lymphocyte cytokinesis block micronucleus assay used and analyzed the correlation between the Nuclear Division Index (NDI), age, blood type and the number of micronuclei (MN). Blood samples were collected from 20 volunteers in heparin tubes, exposed to 2 Gy gamma rays and cultured <i>in vitro</i>. <b>Results:</b> A significant difference in the number of micronuclei between blood group A and blood groups A, B and AB. The Nuclear Division Index (NDI) value for lymphocytes of radiation energy center workers after gamma radiation was significant (1.74±0.1) but still within the normal range. Neither MN frequency nor NDI values correlated with age, but MN frequency showed a correlation with blood type. <b>Conclusion:</b> The gamma irradiation did not induce a cytostatic effect but proved genotoxic to the lymphocytes of radiation energy center workers. Notably, blood type A demonstrated higher sensitivity to gamma radiation.
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  • 本次审查旨在规范和准确评估原料药和药物产品方法和制剂工艺开发中的基因毒性污染物,验证,和降解途径。设计质量(QbD)原则可以应用于现代分析技术的发展使杂质的系统评估和控制,包括风险评估的表现,关键工艺参数(CPP)的筛选,和确定评价与控制方法优化中影响最大的变量。目前在去除基因毒性污染物的困难和这样做的程序已经在这篇综述中概述。以及获得最佳技术和最可接受的配方所需的步骤。除此之外,司,表征,评估,量化,以及基因毒性杂质来源的形成和基因毒性杂质的控制策略,还探讨了在不同工业方法中处理药物产品的亚硝胺含量及其化学计量学前景和相关的最新专利。
    The current review intends to regulate and accurately evaluate genotoxic contaminants in drug substance and drug product method and formulation process development, validation, and degradation pathways. The Quality by Design (QbD) principles can be applied to the systematic evaluation and control of impurities enabled by the development of modern analytical techniques, including the performance of risk assessment, the screening of Critical Process Parameters (CPPs), and the identification of the most influential variables in the optimization of the evaluation and control methods. Current difficulties in removing genotoxic contaminants and the procedures for doing so have been outlined in this review, along with the steps necessary to acquire optimum techniques and the most acceptable formulations. In addition to this, division, characterization, assessment, quantification, and formation of genotoxic impurities sources and control strategy for genotoxic impurities, handling of nitrosamine assay content of drug products in different industrial methodologies and their chemometric prospects and associated recent patents are also explored.
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  • 文章类型: Journal Article
    DNA损伤修复(DDR)是生物体必不可少的过程,有助于基因组的维持和进化。DDR涉及不同的途径,包括同源重组(HR),例如,核苷酸切除修复(NER)和碱基切除修复(BER)。每个途径的活性被揭示与特定的药物诱导病变,但是大多数DNA损伤的修复取决于多种途径的伴随或后续作用。
    在本研究中,我们使用了两种基因毒性抗生素,丝裂霉素C(MMC)和博来霉素(BLM),来破译大肠杆菌中这些不同途径之间的相互作用。我们将基因组方法(TIS和Hi-SC2)和成像测定与遗传解剖相结合。
    我们证明,只有一小部分DDR蛋白对这两种药物引起的病变的修复是共同的。其中,RecN,SMC样蛋白,在修复过程的不同步骤中,通过控制姐妹染色单体动力学和基因组形态发挥重要作用。我们进一步证明,在两种药物诱导的病变处理过程中,RecN对姐妹染色单体动力学的影响并不相同。我们观察到RecN活性和稳定性需要NER对MMC诱导的病变进行预处理,而不是对BLM诱导的病变进行预处理。
    这些结果表明,RecN除了对HR修复双链断裂具有众所周知的重要性外,还在挽救BER途径产生的有毒中间体中起着重要作用。
    UNASSIGNED: DNA damage repair (DDR) is an essential process for living organisms and contributes to genome maintenance and evolution. DDR involves different pathways including Homologous recombination (HR), Nucleotide Excision Repair (NER) and Base excision repair (BER) for example. The activity of each pathway is revealed with particular drug inducing lesions, but the repair of most DNA lesions depends on concomitant or subsequent action of the multiple pathways.
    UNASSIGNED: In the present study, we used two genotoxic antibiotics, mitomycin C (MMC) and Bleomycin (BLM), to decipher the interplays between these different pathways in E. coli. We combined genomic methods (TIS and Hi-SC2) and imaging assays with genetic dissections.
    UNASSIGNED: We demonstrate that only a small set of DDR proteins are common to the repair of the lesions induced by these two drugs. Among them, RecN, an SMC-like protein, plays an important role by controlling sister chromatids dynamics and genome morphology at different steps of the repair processes. We further demonstrate that RecN influence on sister chromatids dynamics is not equivalent during the processing of the lesions induced by the two drugs. We observed that RecN activity and stability requires a pre-processing of the MMC-induced lesions by the NER but not for BLM-induced lesions.
    UNASSIGNED: Those results show that RecN plays a major role in rescuing toxic intermediates generated by the BER pathway in addition to its well-known importance to the repair of double strand breaks by HR.
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  • 文章类型: Journal Article
    水烟吸烟(WTS)是全世界的一个问题,尽管它在中东特别普遍,和东南亚。据报道,吸烟的遗传毒性作用与核异常有关,例如微核(MN),karyorrhexis(KR),核溶解,固缩症,双核,打碎的鸡蛋,脱落的颊粘膜细胞中的凝聚染色质,并且被认为与细胞凋亡有关,与暴露时间无关。
    本研究的目的是评估和比较香烟和WTS对颊粘膜的细胞毒性和遗传毒性作用。
    通过MEDLINE的计算机化文献进行了相关搜索,EMBASE,和公共数据库,其中包括病例控制,关于香烟和WTS在口腔组织中的诱变作用的临床和观察性研究。本研究的数据撤回时间为2010年5月至2022年5月。从搜索数据中总共检索到60篇文章。这项调查已在利雅得榆树大学研究中心注册,以获得机构审查委员会(IRB)的批准,并获得IRB编号\“FRP/2021/448/733/707,有关PROSPERO的系统审查注册号为345417。
    删除副本后,对32人的纳入和排除标准进行了评估。在32篇文章中,二十项研究评估了水烟吸烟者(WTS)和吸烟者口腔粘膜细胞遗传学异常,12人被排除在外。WTS口腔组织中的平均MN水平(1.94±0.39)高于非吸烟者(1.68±0.35)。
    因此,我们得出结论,MN计数可以用作识别吸烟者口腔粘膜变化的生物标志物和初步信号,向癌症形成发展。
    UNASSIGNED: Waterpipe tobacco smoking (WTS) is an issue all over the world, although it is particularly prevalent in the Middle East, and Southeast Asia. The genotoxic effects of smoking were reported to be associated with nucleus abnormalities such as micronuclei (MN), karyorrhexis (KR), karyolysis, pyknosis, binucleates, broken eggs, condensed chromatin in exfoliated buccal mucosal cells, and was believed to be associated with apoptosis of cells and was not correlated to the exposure time.
    UNASSIGNED: The aim of this study was to evaluate and compare the cytotoxic and genotoxic effects of cigarette and WTS on buccal mucosa.
    UNASSIGNED: The pertinent search was done through the computerized literature on MEDLINE, EMBASE, and PUBMED databases, which included case-control, clinical and observational studies regarding the mutagenic effects of cigarettes and WTS in oral tissues. The retraction of data in this study was undertaken from May 2010 to May 2022. A total of 60 articles from the search data were retrieved. This investigation was registered with the research center of Riyadh Elm University for institution review board approval (IRB) and obtained the IRB number \"FRP/2021/448/733/707 and the systematic review registration number with respect to PROSPERO is 345417.
    UNASSIGNED: After the removal of duplicates, 32 were evaluated for the inclusion and exclusion criteria. Out of 32 articles, twenty studies were evaluated for cytogenetic abnormalities in buccal mucosal cells of waterpipe tobacco smokers (WTS) and cigarette smokers, and 12 were excluded. The mean MN levels in the oral tissues of WTS were more (1.94 ± 0.39) than in non-smokers (1.68 ± 0.35).
    UNASSIGNED: Therefore, we conclude that the MN count can be employed as a biomarker and preliminary signal for the identification of changes in oral mucosa among smokers, which develop towards cancer formation.
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  • 文章类型: Journal Article
    硬币金属的配合物可以潜在地用作基于铂的化疗药物的替代品。银是一种硬币金属,可以潜在地提高各种癌症治疗的功效谱,比如恶性黑色素瘤。黑色素瘤是皮肤癌的最具侵袭性的形式,通常在年轻人和中年人中被诊断出来。银具有与皮肤蛋白质的高反应性,并且可以发展为恶性黑素瘤治疗方式。因此,这项研究旨在确定银(I)配合物与氨基硫脲和二苯基(对甲苯基)膦配体的混合配体在人黑色素瘤SK-MEL-28细胞系中的抗增殖和遗传毒性作用。标记为OHBT的一系列银(I)配合物的抗增殖作用,DOHBT,BrOHBT,OHMBT,通过使用磺酰罗丹明B测定法在SK-MEL-28细胞上评估和BrOHMBT。然后,以时间依赖性方式进行DNA损伤分析(30分钟,1h和4h),通过使用碱性彗星测定法研究OHBT和BrOHMBT在其各自的IC50值的遗传毒性。使用膜联蛋白V-FITC/PI流式细胞术测定研究细胞死亡模式。我们目前的发现表明,所有银(I)配合物都显示出良好的抗增殖活性。OHBT的IC50值,DOHBT,BrOHBT,OHMBT,BrOHMBT为2.38±0.3μM,2.70±0.17μM,1.34±0.22μM,2.82±0.45μM,和0.64±0.04μM。然后,DNA损伤分析表明,OHBT和BrOHMBT能够以时间依赖性方式诱导DNA链断裂,OHBT比BrOHMBT更突出。如使用膜联蛋白V-FITC/PI测定所评估的,该效应伴随SK-MEL-28中的凋亡诱导。总之,与氨基硫脲和二苯基(对甲苯基)膦的混合配体的银(I)配合物通过抑制癌细胞生长而发挥抗增殖活性,诱导显著的DNA损伤并最终导致细胞凋亡。
    Complexes of coinage metals can potentially be used as alternatives to platinum-based chemotherapeutic drugs. Silver is a coinage metal that can potentially improve the spectrum of efficacy in various cancers treatment, such as malignant melanoma. Melanoma is the most aggressive form of skin cancer that is often diagnosed in young and middle-aged adults. Silver has high reactivity with skin proteins and can be developed as a malignant melanoma treatment modality. Therefore, this study aims to identify the anti-proliferative and genotoxic effects of silver(I) complexes with mixed-ligands of thiosemicarbazones and diphenyl(p-tolyl)phosphine ligands in the human melanoma SK-MEL-28 cell line. The anti-proliferative effects of a series of silver(I) complex compounds labelled as OHBT, DOHBT, BrOHBT, OHMBT, and BrOHMBT were evaluated on SK-MEL-28 cells by using the Sulforhodamine B assay. Then, DNA damage analysis was performed in a time-dependent manner (30 min, 1 h and 4 h) by using alkaline comet assay to investigate the genotoxicity of OHBT and BrOHMBT at their respective IC50 values. The mode of cell death was studied using Annexin V-FITC/PI flow cytometry assay. Our current findings demonstrated that all silver(I) complex compounds showed good anti-proliferative activity. The IC50 values of OHBT, DOHBT, BrOHBT, OHMBT, and BrOHMBT were 2.38 ± 0.3 μM, 2.70 ± 0.17 μM, 1.34 ± 0.22 μM, 2.82 ± 0.45 μM, and 0.64 ± 0.04 μM respectively. Then, DNA damage analysis showed that OHBT and BrOHMBT could induce DNA strand breaks in a time-dependent manner, with OHBT being more prominent than BrOHMBT. This effect was accompanied by apoptosis induction in SK-MEL-28, as evaluated using Annexin V-FITC/PI assay. In conclusion, silver(I) complexes with mixed-ligands of thiosemicarbazones and diphenyl(p-tolyl)phosphine exerted anti-proliferative activities by inhibiting cancer cell growth, inducing significant DNA damage and ultimately resulting in apoptosis.
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