Genotoxicity

遗传毒性
  • 文章类型: Journal Article
    射频(RF)源的广泛使用,从家用电器到电信设备和军事装备,引起人们和监管机构对RF暴露的潜在健康风险的担忧。因此,已经进行了一些体外和体内研究,以研究其生物学效应,特别是非热的,这种非电离辐射。迄今为止,由于已经报道了有争议的结果,这个问题仍在辩论中。此外,不同的射频信号调制对生物系统的影响仍然缺乏研究。本体外研究旨在评估人真皮成纤维细胞(HDF)中连续或脉冲1.6GHzRF的细胞毒性和遗传毒性。
    HDF培养物暴露于连续和脉冲的1.6GHz射频,2小时,与0.4W/kg的比吸收率(SAR)。1.6GHz射频对HDF的潜在生物学效应采用多方法学方法进行了评估,分析对细胞周期的影响,超微结构,蛋白质表达,有丝分裂纺锤体,CREST染色的微核,染色体分离和γ-H2AX/53BP1灶。
    1.6GHzRF暴露修饰了HDF的蛋白质表达和形态。具体来说,不同热休克蛋白(HSP)的表达(即HSP-90,HSP-60和HSP-25)和磷酸-AKT受到影响。此外,连续和脉冲RF都改变了HDF中的细胞骨架组织并增加了溶酶体的数量,而自噬体的形成仅在脉冲RF暴露后观察到。暴露后还发现有丝分裂纺锤体异常。然而,对细胞周期没有显著影响,染色体分离,CREST染色的微核和γ-H2AX/53BP1灶。
    本研究的结果表明,在1.6GHz射频暴露的HDF中没有基因毒性损伤,尽管观察到有丝分裂纺锤体改变,它们没有不良作用。另一方面,暴露的HDF中某些蛋白质表达和细胞超微结构的变化表明,RF可能在形态和分子水平上诱导细胞改变。
    UNASSIGNED: The widespread use of radiofrequency (RF) sources, ranging from household appliances to telecommunications devices and military equipment, raises concerns among people and regulatory agencies about the potential health risks of RF exposure. Consequently, several in vitro and in vivo studies have been done to investigate the biological effects, in particular non-thermal, of this non-ionizing radiation. To date, this issue is still being debated due to the controversial results that have been reported. Furthermore, the impact of different RF signal modulations on biological systems remains poorly investigated. The present in vitro study aims to evaluate the cytotoxicity and genotoxicity of continuous or pulsed 1.6 GHz RF in human dermal fibroblasts (HDF).
    UNASSIGNED: HDF cultures were exposed to continuous and pulsed 1.6 GHz RF, for 2 h, with Specific Absorption Rate (SAR) of 0.4 W/kg. The potential biological effects of 1.6 GHz RF on HDF were assessed with a multi-methodological approach, analyzing the effects on cell cycle, ultrastructure, protein expression, mitotic spindle, CREST stained micronuclei, chromosome segregation and γ-H2AX/53BP1 foci.
    UNASSIGNED: 1.6 GHz RF exposure modified proteins expression and morphology of HDF. Specifically, the expression of different heat-shock proteins (HSP) (i.e., HSP-90, HSP-60, and HSP-25) and phospho-AKT were affected. In addition, both continuous and pulsed RF modified the cytoskeletal organization in HDF and increased the number of lysosomes, while the formation of autophagosomes was observed only after pulsed RF exposure. Mitotic spindle anomalies were also found after exposure. However, no significant effect was observed on cell cycle, chromosome segregation, CREST-stained micronuclei and γ-H2AX/53BP1 foci.
    UNASSIGNED: The results of the present study show the absence of genotoxic damage in 1.6 GHz RF exposed HDF and, although mitotic spindle alterations were observed, they did not have an aneugenic effect. On the other hand, changes in some proteins expression and cell ultrastructure in exposed HDF suggest that RF can potentially induce cell alterations at the morphological and molecular levels.
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  • 文章类型: Journal Article
    背景:电子烟(电子烟)通常被宣传为传统吸烟的更安全的替代品。然而,最近的数据表明,它们可能不像以前认为的那样安全。本研究旨在评估电子烟液体的遗传毒性和致突变性。
    方法:我们从吉达当地市场随机选择了8种电子烟液,沙特阿拉伯。我们使用遗传毒性SOS-ChromoTest™试剂盒评估了它们的遗传毒性。在这次调查中,大鼠肝脏S9部分用于模拟肝脏代谢功能,以测量任何化学物质的诱变潜力。通过记录有和没有代谢活化酶(S-9)的β-半乳糖苷酶和碱性磷酸酶活性来进行SOS-染色体测试。
    结果:所有样本,除了样品2的前两个稀释液,在没有S9激活酶的情况下是无遗传毒性的,根据基因毒性分析。然而,当在S9酶存在下测试时,样品2、4和7在不同浓度下表现出诱变活性。
    结论:与普遍看法相反,电子烟不安全。本调查证实了某些电子烟液体中存在有毒物质和致癌物质。这种暴露可能会增加使用者患各种健康并发症的风险。
    BACKGROUND: Electronic cigarettes (e-cigarettes) are often advertised as a safer alternative to traditional smoking. However, recent data suggest they may not be as safe as previously believed. This study aims to evaluate the genotoxicity and mutagenicity of e-cigarette liquids.
    METHODS: We randomly selected eight varieties of e-cigarette liquids from the local market in Jeddah, Saudi Arabia. We evaluated their genotoxicity using the Genotoxicity SOS-Chromo Test™ Kit. In this investigation, a rat liver S9 fraction was utilized to emulate liver metabolic function to measure any chemical substance\'s mutagenic potential. The SOS-Chromo Test was performed by recording the β-galactosidase and alkaline phosphatase activity with and without the metabolic activation enzyme (S-9).
    RESULTS: All samples, except for the first two dilutions of sample 2, were nongenotoxic in the absence of the S9 activation enzyme, according to the genotoxicity analysis. However, when tested in the presence of the S9 enzyme, samples 2, 4, and 7 exhibited mutagenic activity at varying concentrations.
    CONCLUSIONS: Contrary to common belief, e-cigarettes are not safe. The present investigation confirms the presence of both toxicants and carcinogens in some e-cigarette liquids. This exposure could increase users\' risk of various health complications.
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  • 文章类型: Journal Article
    评估化学品的诱变特性对于了解其潜在的癌症风险至关重要。最近基于Illumina的错误校正测序技术已经使得能够直接检测由诱变剂从头诱导的突变。然而,由于Illumina平台缺乏内在的纠错能力,复杂的文库制备和生物信息学过程对于鉴定这些罕见的突变是必要的。在这项研究中,我们评估了基于PacBio的长读数HiFi测序(HiFiseq),集成了纠错,可以检测到C57BL/6小鼠组织中诱变剂诱导的从头突变。使用HiFiseq,在暴露于7,12-二甲基苯并[a]蒽的小鼠组织中发现了突变频率的剂量依赖性增加,丙卡巴嗪,和N-丙基-N-亚硝基脲。此外,来自这些暴露的突变特征与先前报道的这些诱变剂的突变特征一致。这项研究表明,HiFiseq可以补充已建立的突变检测试验,以促进危险化合物的鉴定。
    Evaluating the mutagenic properties of chemicals is crucial for understanding their potential cancer risks. Recent Illumina-based error-corrected sequencing techniques have enabled the direct detection of mutations induced de novo by mutagens. However, as the Illumina platform lacks intrinsic error-correction capabilities, complex library preparations and bioinformatic processes are necessary to identify these rare mutations. In this study, we evaluated whether long-read PacBio-based HiFi sequencing (HiFi seq), which has integrated error-correction, can detect de novo mutations induced by mutagens in C57BL/6 mouse tissues. Using HiFi seq, dose-dependent increases in mutation frequencies were found in tissues from mice exposed to 7,12-dimethylbenz[a]anthracene, procarbazine, and N-propyl-N-nitrosourea. Furthermore, the mutational signatures derived from these exposures were consistent with those previously reported for these mutagens. This study demonstrates that HiFi seq can complement established mutation detection assays to facilitate the identification of hazardous compounds.
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  • 文章类型: Journal Article
    噻虫啉,一种危险的新烟碱杀虫剂,在日常农业实践中普遍存在,由于其残留物对食品的有害影响,引起了人们的关注,并且对非预期生物构成了对人类健康的重大威胁。Thiacloprid于1990年推出,因其可感知的有效性和降低非目标动物的风险而受到欢迎。然而,近年来的新兴研究报道了噻虫啉对非靶标物种的显著毒性作用,跨神经毒性,免疫毒性,肝毒性,肾毒性,和生殖问题。哺乳动物研究,特别是涉及啮齿动物,揭示认知障碍,海马损伤,和接触噻虫啉后的肝脏异常。生殖毒性和DNA损伤是迫在眉睫的问题,破坏妊娠表观遗传重编程,并暗示对后代的持续影响。遗传毒性效应,胚胎毒性,并观察到生殖毒性,强调了在使用噻虫啉时需要谨慎。这篇综述强调了近年来报道的噻虫啉产生的毒性作用,挑战其对脊椎动物毒性较低的最初信念。
    Thiacloprid, a hazardous neonicotinoid insecticide, prevalent in daily agricultural practices, raises concerns due to the harmful effects of its residues on food items, and on unintended organisms poses a significant threat to human health. Introduced in 1990, Thiacloprid have gained popularity for its perceived effectiveness and reduced risks to non-target animals. However, emerging research in recent years reports significant toxic effects of Thiacloprid on non-target species, spanning neurotoxicity, immunotoxicity, hepatotoxicity, nephrotoxicity, and reproductive issues. Mammalian studies, particularly involving rodents, reveal cognitive impairment, hippocampal damage, and hepatic abnormalities upon Thiacloprid exposure. Reproductive toxicity and DNA damage are imminent concerns, disrupting gestational epigenetic reprogramming and suggesting persistent effects on future generations. Genotoxic effects, Embryotoxic, and observed reproductive toxicity accentuate the need for caution in the utilization of Thiacloprid. This review highlights reported toxic effects produced by Thiacloprid in recent years, challenging the initial belief in its lower toxicity for vertebrates.
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  • 文章类型: Journal Article
    双酚广泛用于聚碳酸酯塑料和树脂涂料的生产。双酚A(BPA)被认为会引起广泛的不良影响和“低剂量毒性”。随着寻找BPA的替代物质,其他双酚衍生物,即双酚F(BPF)和双酚S(BPS)的使用已经增加。
    在当前的研究中,我们旨在评估双酚衍生物对免疫和凋亡标志物以及HepG2细胞DNA损伤的计算机预测抑制浓度50(pIC50)。此外,凋亡,BPA的遗传毒性和免疫毒性作用,比较测定了BPF和BPS。通过检测不同的caspase活性来评估双酚对细胞凋亡的影响。通过测量8-羟基-2'-脱氧鸟苷(8-OHdG)和8-氧鸟嘌呤糖基化酶(OGG1)的水平来评估双酚的遗传毒性作用。为了确定双酚衍生物的免疫毒性作用,白细胞介素4(IL-4)和白细胞介素10(IL-10)的水平,转化生长因子-β(TGF-β)和肿瘤坏死因子-α(TNF-α),已知由HepG2细胞表达,被测量。结果:计算机数据表明,低剂量下所有双酚都可能导致免疫和凋亡标志物的改变以及DNA损伤。体外数据显示,所有双酚衍生物在抑制浓度30s(IC30s)下都能影响免疫标记。此外,BPF和BPS也可能具有凋亡免疫毒性作用。
    需要进一步进行计算机和体内研究,以检查替代双酚衍生物的毒性作用。
    UNASSIGNED: Bisphenols are widely used in the production of polycarbonate plastics and resin coatings. Bisphenol A (BPA) is suggested to cause a wide range of unwanted effects and \"low dose toxicity\". With the search for alternative substances to BPA, the use of other bisphenol derivatives namely bisphenol F (BPF) and bisphenol S (BPS) has increased.
    UNASSIGNED: In the current study, we aimed to evaluate the in silico predicted inhibitory concentration 50s (pIC50s) of bisphenol derivatives on immune and apoptotic markers and DNA damage on HepG2 cells. Moreover, apoptotic, genotoxic and immunotoxic effects of BPA, BPF and BPS were determined comparatively. Effects of bisphenols on apoptosis were evaluated by detecting different caspase activities. The genotoxic effects of bisphenols were evaluated by measuring the levels of 8-hydroxy-2\'-deoxyguanosine (8-OHdG) and 8-oxoguanine glycosylase (OGG1). To determine the immunotoxic effect of bisphenol derivatives, the levels of interleukin 4 (IL-4) and interleukin 10 (IL-10), transforming growth factor beta (TGF-β) and tumor necrosis factor-alpha (TNF-α), which are known to be expressed by HepG2 cells, were measured. Results: In silico data indicate that all of the bisphenols may cause alterations in immune and apoptotic markers as well as DNA damage at low doses. İn vitro data revealed that all bisphenol derivatives could affect immune markers at inhibitory concentration 30s (IC30s). In addition, BPF and BPS may also have apoptotic immunotoxic effects.
    UNASSIGNED: Both in silico and in vivo research are needed further to examine the toxic effects of alternative bisphenol derivatives.
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  • 文章类型: Journal Article
    合成食品染料在食品中呈指数级使用,有关其毒性和安全性的研究很少引起人们的关注。赤藓红是用于果酱的合成食品染料之一,无花果,菠萝果酱,乳制品,软饮料,泡菜,津津有味,熏鱼,奶酪,番茄酱,maraschino樱桃和各种其他食物。
    在这项研究中,评估了赤藓红的细胞遗传毒性作用,使用洋葱根分生组织细胞以0.1、0.25、0.5和1mg/mL的浓度进行细胞和分子交替。
    结果表明,在0.1mg/mL浓度下96小时后,有丝分裂指数显着降低了57.81%。在生化分析中,丙二醛含量显着增加(5.47倍),而脯氨酸含量,过氧化氢酶活性和超氧化物歧化酶活性以浓度依赖性方式逐渐下降,最大下降78.11%,96h后最高浓度分别为64.68%和61.73%。彗星分析显示,随着浓度的增加,DNA损伤增加,衰减的全反射-傅立叶变换红外光谱(ATR-FTIR)分析显示生物分子发生了显着变化,如多元分析所示。即主成分分析(PCA)。此外,分子对接显示出强结合能(Gbest=-11.46kcal/mol)和在赤藓和DNA小沟之间的抑制常数(Ki)为3.96nM。
    本研究的发现揭示了赤霉素对A.cepa根细胞的细胞毒性和遗传毒性潜力。Further,该研究还提出了A.cepa作为研究食品添加剂毒性的模型系统的有用性。
    UNASSIGNED: Synthetic food dyes are being exponentially used in food products and scarce studies regarding their toxicities and safety raise concern. Erythrosine is one of the synthetic food dyes being used in jams, fig, pineapple marmalades, dairy products, soft drinks, pickles, relishes, smoked fish, cheese, ketchup, maraschino cherries and a variety of other foods.
    UNASSIGNED: In this study the cyto-genotoxic effect of erythrosine was evaluated, using root meristematic cells of Allium cepa for the cellular and molecular alternations at concentrations 0.1, 0.25, 0.5 and 1 mg/mL.
    UNASSIGNED: The results revealed a significant decrease of 57.81% in the mitotic index after 96 h at the 0.1 mg/mL concentration. In biochemical analysis, the malondialdehyde content increased significantly (5.47-fold), while proline content, catalase activity and superoxide dismutase activity decreased gradually in a concentration-dependent manner showing a maximum decrease of 78.11%, 64.68% and 61.73% respectively at the highest concentration after 96 h duration. The comet assay revealed increased DNA damage with increasing concentration and attenuated total reflectance- Fourier transform infrared spectroscopy (ATR-FTIR) analysis showed significant alterations in biomolecules as indicated by multivariate analysis, i.e. Principal Component Analysis (PCA). Furthermore, molecular docking demonstrated a strong binding energy (Gbest = -11.46 kcal/mol) and an inhibition constant (Ki) of 3.96 nM between erythrosine and the DNA minor groove.
    UNASSIGNED: The present study\'s findings revealed the cytotoxic and genotoxic potential of erythrosine on A. cepa root cells. Further, the study also proposed the usefulness of A. cepa as a model system for studying the toxicity of food additives.
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  • 文章类型: Journal Article
    香草属对全球食品生产至关重要,香水,和制药行业。然而,剥削威胁着一些物种,导致灭绝。传统社区将香草用于医疗目的,还有一些物种,如VanillachamissonisKlotzsch和VanillabahianaHoehne,具有占领市场的潜力。为此,与Vanillaplanifolia一起进行了这两个上述物种的甲醇提取。分析细胞活力,进行诱变和基因毒性潜力。在艾姆斯测试中,在浓度为0.5和5000μg/ml的情况下对5个菌株进行测定。在TA98菌株中,只有香草在最高浓度下表现出诱变性。在0.05-5000µg/ml的剂量范围内以及24、48和72小时的暴露时间内进行生存能力测试。可以观察到仅在最高浓度下观察到的细胞活力降低。所有三种物种和两种细胞类型的测试。通过胞质分裂阻滞微核试验,以0.5至500µg/ml的浓度评估提取物的遗传毒性诱导。核分裂指数(NDI)无基因毒性损害或减少。这项研究没有发现诱变性,细胞毒性,或所测试物种的遗传毒性,表明人类可能用于食品或制药目的。
    The Vanilla genus is crucial for global production in food, perfume, and pharmaceutical industries. However, exploitation threatens some species, leading to extinction. Traditional communities use vanilla for medicinal purposes, and there are species like Vanilla chamissonis Klotzsch and Vanilla bahiana Hoehne with potential to occupy the market. For this, methanolic extraction of these two mentioned species was conducted alongside Vanilla planifolia. Analyzes of the cell viability, mutagenic and genotoxic potential were performed. In the Ames test, the assays were performed with concentrations from 0.5 and 5000 μg/ml and on five strains. Only Vanilla planifolia exhibited mutagenicity at the highest concentration in the TA98 strain. Viability tests were performed within a dose range of 0.05-5000 µg/ml and 24, 48, and 72-hour exposures. It was possible to observe a reduction in cell viability observed only at the highest concentration, for all three species and both cell types tested. Genotoxicity induction by the extracts was assessed at concentrations from 0.5 to 500 µg/ml through the cytokinesis-block micronucleus assay. No genotoxic damage or reduction in the Nucleus Division Index (NDI). The study found no mutagenicity, cytotoxicity, or genotoxicity in the species tested, indicating potential human use for food or pharmaceutical purposes.
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  • 文章类型: Journal Article
    背景:缬草,俗称“缬草”,是一种分布在美国北温带地区的传统草药,欧洲和亚洲。在中医中,缬草和它的根被用于治疗心脏和心灵的不安,心悸和失眠引起的内部抑郁的情绪和情绪。然而,缬草的安全性评价尚不清楚。
    目的:本研究旨在评估遗传毒性,14天急性口服毒性试验,缬草根水提物(AEVR)90天亚慢性经口毒性试验和致畸试验。
    方法:用细菌回复突变评估AEVR的遗传毒性,小鼠红细胞微核试验和体外哺乳动物细胞染色体畸变试验。在14天的急性毒性研究中,昆明小鼠以96g/kg体重的剂量通过管饲法给药。在90天的亚慢性毒性研究中,Sprague-Dawley大鼠接受0、3.5、7和14g/kg体重的AEVR口服剂量。在致畸研究中,怀孕的Sprague-Dawley大鼠接受剂量为0、3.5、7和14g/kg体重的AEVR。
    结果:AEVR没有显示任何基于细菌反向突变的遗传毒性,小鼠红细胞微核试验和体外哺乳动物细胞染色体畸变试验。在急性毒性研究中,96g/kg体重剂量的AEVR不会导致雄性或雌性小鼠的死亡或异常行为。在亚慢性毒性研究中,在0、3.5、7、14克/千克体重的剂量下,对临床观察没有剂量相关影响,体重,器官重量,血液学,在雄性或雌性大鼠中检测AEVR的血清生化和尿液分析。致畸试验显示胚胎形成无明显毒理学变化,怀孕大鼠的体重,外部,在剂量为0、3.5、7、14g/kg体重的孕鼠和胎鼠中观察到的骨骼和内脏检查。
    结论:体内或体外试验证明AEVR不表现出遗传毒性。根据急性口服毒性研究,在两种性别的小鼠中,AEVR的LD50均大于96g/kg体重。亚慢性毒性和致畸试验表明,AEVR的无观察不良反应水平(NOAEL)不低于14g/kg体重。本研究建立了AEVR的无毒剂量,为在一些国家和地区使用缬草作为新资源食品提供了基础。
    BACKGROUND: Valeriana officinalis L., commonly known as \"valerian\", is a traditional herbal medicine distributed in the north temperate zones of America, Europe and Asia. In traditional Chinese medicine, valerian and its roots were used for the treatment of restlessness of the heart and mind, palpitation and insomnia caused by internal depression of emotions and moods. However, safety evaluation of valerian remains deeply unclear.
    OBJECTIVE: This study aimed to evaluate the genotoxicity, 14-days acute oral toxicity test, 90-day subchronic oral toxicity test and teratogenicity test of aqueous extract of valerian root (AEVR).
    METHODS: The genotoxicity of AEVR was evaluated with bacterial reverse mutation, mouse erythrocyte micronucleus test and in vitro mammalian cell chromosome aberration test. In the 14-days acute toxicity study, Kunming mice were administered at a dosage of 96 g/kg body weigh by gavage. In the 90-day subchronic toxicity study, Sprague-Dawley rats received oral doses of 0, 3.5, 7 and 14 g/kg body weight of AEVR. In the teratogenicity study, pregnant Sprague-Dawley rats received a dose of 0, 3.5, 7 and 14 g/kg body weight of AEVR.
    RESULTS: AEVR did not show any genotoxicity based on the bacterial reverse mutation, mouse erythrocyte micronucleus test and in vitro mammalian cell chromosome aberration test. In the acute toxicity study, AEVR at a dose of 96 g/kg body weight did not cause death or abnormal behavior in male or female mice. In the subchronic toxicity study, at the doses of 0, 3.5, 7, 14 g/kg body weight, no dose-related effects on clinical observation, body weight, organ weight, hematology, serum biochemistry and urinalysis of AEVR were detected in male or female rats. Teratogenicity test shown that there were no significant toxicologically changes in embryonic formation, body weight of pregnant rats, external, skeletal and visceral examination observed in pregnant and fetal rats at the dosage of 0, 3.5, 7, 14 g/kg body weight.
    CONCLUSIONS: In vivo or in vitro assays demonstrated that AEVR does not exhibit genotoxicity. The LD50 of AEVR was greater than 96 g/kg body weight in both sex of mice according to acute oral toxicity study. Subchronic toxicity and teratogenicity tests showed that the no observed adverse effect level (NOAEL) of AEVR was no less than 14 g/kg body weight. This study established a non-toxic dose of AEVR, providing a foundation for the use of valerian as a new resource food in some countries and regions.
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  • 文章类型: Journal Article
    三端孢霉烯是天然存在的化学物质,由真菌产生,可以在受污染的作物中找到。单孢霉烯有可能间接损伤DNA并加剧基因毒性剂的基因毒性作用。然而,大多数单端孢霉烯的遗传毒性数据有限,数据差距仍然存在。在这里,我们使用γH2AX/pH3测定法来评估13种单孢霉烯的体外DNA损伤。三种人类细胞系(SH-SY5Y,ACHN,和HepG2)暴露于每个单端孢菌(0.001-100μM),以评估作为大脑模型的毒性,肾,还有肝脏,分别。浓度依赖性诱导DNA损伤,以γH2AX诱导为例,观察到所有的单端孢霉烯。采用体外-体内外推(IVIVIVE)建模来支持体内等效效能排序和潜在风险筛选。二乙酰氧西林,T-2和HT-2具有最高的基因毒性,特别是在SH-SY5Y细胞。将IVIVE的等效剂量(AED)与法国总饮食研究的暴露数据进行比较,以评估潜在风险。来自SH-SY5Y模型的T-2和HT-2的AED在一岁或更小的婴儿的暴露水平的100倍以内。总的来说,在婴儿中,单端孢霉烯类可能会损伤DNA和更高的暴露量,这突出表明有必要研究整个更广泛的单端孢霉烯家族的累积效应.
    Trichothecenes are naturally occurring chemicals, produced by fungi, that can be found in contaminated crops. Trichothecenes have the potential to indirectly damage DNA and exacerbate genotoxic effects of genotoxicants. However, genotoxicity data for most trichothecenes are limited and data gaps remain. Here we use the γH2AX/pH3 assay to evaluate DNA damage in vitro of 13 trichothecenes. Three human cell lines (SH-SY5Y, ACHN, and HepG2) were exposed to each trichothecene (0.001-100 μM) to assess toxicity as models for the brain, kidney, and liver, respectively. Concentration-dependent induction of DNA damage, illustrated by γH2AX induction, was observed for all trichothecenes. In vitro-in vivo extrapolation (IVIVE) modeling was employed to support in vivo equivalent potency ranking and screen for risk potential. Diacetoxyscirpenol, T-2, and HT-2 had the highest genotoxic potency, notably in SH-SY5Y cells. Administered equivalent doses (AEDs) derived from IVIVE were compared against exposure data from French total diet studies to assess risk potential. AEDs derived for T-2 and HT-2 from the SH-SY5Y model were within 100-fold of exposure levels for infants aged one year or less. Overall, the potential for trichothecenes to damage DNA and higher exposures in infants highlights the need to investigate the cumulative effects across the broader trichothecene family.
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  • 文章类型: Journal Article
    银纳米粒子(AgNPs)的毒性取决于它们的物理化学性质。正在进行的研究旨在开发使用分子修饰AgNPs的有效方法,这些分子能够控制正常细胞和癌细胞中纳米粒子诱导的过程。氨基酸稳定的纳米颗粒的应用似乎很有前景,表现出可调的电动特性。因此,这项研究的重点是确定半胱氨酸(CYS)稳定的AgNPs的表面电荷对其对人类正常B(COLO-720L)和T(HUT-78)淋巴细胞系的毒性的影响。通过化学还原合成CYS-AgNP。透射电子显微镜(TEM)成像显示,它们表现出平均尺寸为18±3nm的准球形。CYS-AgNPs在弱酸性(pH4.0)和碱性(7.4和9.0)条件下保持稳定,在pH5.1时观察到等电点。用CYS-AgNPs处理淋巴细胞24小时后,观察到细胞形态的浓度依赖性改变。带正电荷的CYS-AgNP显著降低淋巴细胞活力。此外,与带负电荷的CYZ-AgNP相比,它们表现出更大的遗传毒性和更明显的生物膜破坏。尽管两种类型的AgNPs与胎牛血清(FBS)相互作用相似,并且显示出银离子释放的可比曲线,生物测定一致显示,带正电荷的CYS-AgNPs在所有研究的细胞水平上都发挥了更强的作用.尽管两种类型的CYS-AgNP在其稳定层中具有相同的化学结构,pH诱导的表面电荷变化显着影响其生物活性。
    The toxicity of silver nanoparticles (AgNPs) depends on their physicochemical properties. The ongoing research aims to develop effective methods for modifying AgNPs using molecules that enable control over the processes induced by nanoparticles in both normal and cancerous cells. Application of amino acid-stabilized nanoparticles appears promising, exhibiting tunable electrokinetic properties. Therefore, this study focused on determining the influence of the surface charge of cysteine (CYS)-stabilized AgNPs on their toxicity towards human normal B (COLO-720L) and T (HUT-78) lymphocyte cell lines. CYS-AgNPs were synthesized via the chemical reduction. Transmission electron microcopy (TEM) imaging revealed that they exhibited a quasi-spherical shape with an average size of 18 ± 3 nm. CYS-AgNPs remained stable under mild acidic (pH 4.0) and alkaline (7.4 and 9.0) conditions, with an isoelectric point observed at pH 5.1. Following a 24 h treatment of lymphocytes with CYS-AgNPs, concentration-dependent alterations in cell morphology were observed. Positively charged CYS-AgNPs notably decreased lymphocyte viability. Furthermore, they exhibited grater genotoxicity and more pronounced disruption of biological membranes compared to negatively charged CYZ-AgNPs. Despite both types of AgNPs interacting similarly with fetal bovine serum (FBS) and showing comparable profiles of silver ion release, the biological assays consistently revealed that the positively charged CYS-AgNPs exerted stronger effects at all investigated cellular levels. Although both types of CYS-AgNPs have the same chemical structure in their stabilizing layers, the pH-induced alterations in their surface charge significantly affect their biological activity.
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