Genotoxicity

遗传毒性
  • 文章类型: Journal Article
    甲醛是一种能够保存细胞和组织形态的化合物,在全球范围内广泛用于工业和医疗过程。然而,由于一个人长期暴露于甲醛后发生的许多生物效应,这种化合物对职业暴露的工人构成更大的癌症风险,即使浓度较低。因此,本系统综述旨在了解在接触甲醛的个体中,多态性(个体易感性)与遗传毒性是否存在正相关.为此,共有8项选定的研究由两名评审员仔细分析,他们根据使用的分析参数为每项研究评分。首先,所有研究都调查了甲醛暴露下的病理学家或解剖实验室病理学工作者。此外,在质量评估中,大多数研究被归类为中度或重度.结果显示,暴露于甲醛的个体中某些多态性与遗传毒性之间存在正相关,因为超过一半的研究观察到遗传毒性与异源生物代谢基因的多态性之间存在正相关。我们了解这些参数会影响个体对外周血中甲醛引起的基因组损伤的易感性。总之,具有某些基因型的个体可能表现出更高或更低的DNA损伤和/或更低或更高的DNA修复潜力。
    Formaldehyde is a chemical compound capable of preserving cells and tissue morphology, being extensively used worldwide in industrial and medical processes. However, due to the many biological effects that take place after an individual is chronically exposed to formaldehyde, this compound poses a greater cancer risk for workers under its occupational exposure, even at lower concentrations. Thus, the present systematic review aimed to understand whether there may be a positive relation between polymorphism (in terms of individual susceptibility) and genotoxicity in individuals occupationally exposed to formaldehyde. For this purpose, a total of eight selected studies were carefully analyzed by two reviewers, who attributed scores to each study according to the used analysis parameters. First, all studies investigated either pathologists under formaldehyde exposure or anatomical laboratory pathology workers. In addition, the majority of studies were categorized as moderate or strong in the quality assessment. The results revealed a positive association between some polymorphism and genotoxicity in individuals exposed to formaldehyde, since more than half of the studies observed positive relations between genotoxicity and polymorphisms in xenobiotics metabolizing genes. We understand such parameters influence individuals\' susceptibility to genomic damage induced by formaldehyde in peripheral blood. In conclusion, individuals with certain genotypes may show higher or lower DNA damage and/or lower or higher DNA repair potential.
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  • 文章类型: Journal Article
    过渡金属镉(Cd)对人体有毒,可引起细胞氧化还原应激和炎症。Cd是一种公认的致癌物质,但与其遗传毒性和致癌性相关的分子机制尚不明确。因此,进行了系统的审查,以审查已经涵盖Cd遗传毒性的分子机制及其与细胞氧化还原应激和炎症的关系的科学文献。PubMed的电子数据库搜索,Scopus,并进行了WebofScienceCoreCollection,以检索调查Cd遗传毒性是否与氧化还原应激和炎症的诱导直接相关的研究。研究包括通过体外和体内给药途径暴露于Cd。在检索到的214种出版物中,10符合本次审查的纳入标准。临床前研究表明,Cd暴露会导致活性氧(ROS)的诱导,通过转录因子NF-κβ的伴随活性,诱导促炎细胞因子的产生和与诱导过敏反应一致的细胞因子谱。关于Cd对细胞信号转导途径的影响的信息有限,这与遗传毒性的关系仍然没有定论。然而,与抗氧化剂预孵育,N-乙酰半胱氨酸或萝卜硫烷,或者坏死性凋亡抑制剂,necrostatin-1可降低Cd毒性;表明这些药物在Cd中毒的情况下可能是有益的治疗辅助手段。总的来说,这篇综述强调了Cd诱导的毒性和相关的组织病理学,以及最终Cd的致癌潜力,可能由氧化还原应激和炎症机制驱动。
    The transition metal cadmium (Cd) is toxic to humans and can induce cellular redox stress and inflammation. Cd is a recognized carcinogen, but the molecular mechanisms associated with its genotoxicity and carcinogenicity are not defined. Therefore, a systematic review was undertaken to examine the scientific literature that has covered the molecular mechanism of Cd genotoxicity and its relationship to cellular redox stress and inflammation. An electronic database search of PubMed, Scopus, and the Web of Science Core Collection was conducted to retrieve the studies that had investigated if Cd genotoxicity was directly linked to the induction of redox stress and inflammation. Studies included exposure to Cd via in vitro and in vivo routes of administration. Of 214 publications retrieved, 10 met the inclusion criteria for this review. Preclinical studies indicate that Cd exposure causes the induction of reactive oxygen species (ROS) and, via concomitant activity of the transcription factor NF-κβ, induces the production of pro-inflammatory cytokines and a cytokine profile consistent with the induction of an allergic response. There is limited information regarding the impact of Cd on cellular signal transduction pathways, and the relationship of this to genotoxicity is still inconclusive. Nevertheless, pre-incubation with the antioxidants, N-acetylcysteine or sulforaphane, or the necroptosis inhibitor, necrostatin-1, reduces Cd toxicity; indicative that these agents may be a beneficial treatment adjunct in cases of Cd poisoning. Collectively, this review highlights that Cd-induced toxicity and associated tissue pathology, and ultimately the carcinogenic potential of Cd, may be driven by redox stress and inflammatory mechanisms.
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  • 文章类型: Journal Article
    这篇综述的目的是研究彗星测定法在洋葱根细胞中的应用,以评估环境样品的遗传毒性并分析所采用的实验程序。使用组合搜索词“彗星测定”和“洋葱”从在线数据库中选择2000年1月至2023年10月之间发表的文章进行了文献检索。只有18篇论文符合纳入标准。这些都没有在前八年(2000-2007年)发表,强调在过去十年中,人们越来越有兴趣在洋葱上使用彗星测定法来分析环境样本。大多数选定的研究(15/18,83%)是在洋葱鳞茎上属于水室的样品上进行的。进行了一半的选定研究(9/18)以证明样品的DNA损伤作用,而另一半的研究不仅认识到遗传毒性剂的存在,而且还讨论了可能的补救措施。对实验程序的详细分析揭示了许多关键步骤的异质性,例如暴露时间,测试控件,原子核隔离解决方案,电泳持续时间,原子核数得分。这篇文献综述表明,洋葱上的彗星试验,虽然被认为是一种适当的工具,在环境毒理学中没有得到充分利用。更大的标准化可能会导致其更广泛的使用,提供有关环境样品的遗传毒性以及不同过程减轻其对植物的负面影响的能力的有价值信息。
    The purposes of this review were to investigate the application of the comet assay in Allium cepa root cells to assess the genotoxicity of environmental samples and to analyse the experimental procedures employed. A literature search was performed selecting articles published between January 2000 and October 2023 from online databases using the combined search terms \"comet assay\" and \"Allium cepa\". Only 18 papers met the inclusion criteria. None of these were published in the first eight years (2000-2007), highlighting the increasing interest in using the comet assay on Allium cepa to analyse environmental samples over the last decade. The majority of the selected studies (15/18, 83%) were performed on samples belonging to the water compartment on onion bulbs. Half of the selected studies (9/18) were conducted to demonstrate the DNA damaging effect of the sample, while the other half of the studies not only recognized the presence of genotoxic agents but also addressed possible remediation measures. Detailed analysis of the experimental procedures revealed heterogeneity in many key steps, such as exposure time, test controls, nuclei isolation solutions, duration of electrophoresis, number of nuclei scored. This literature review has shown that the comet assay on Allium cepa, although recognized as an appropriate tool, is underutilized in environmental toxicology. Greater standardization could lead to its more widespread use, providing valuable information on the genotoxicity of environmental samples and the ability of different processes to mitigate their negative effects on plants.
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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
    背景:迷迭香(迷迭香)含有生物碱,酚酸,皂苷,单宁,二萜,黄酮类化合物,和精油,并具有抗氧化剂,抗炎,抗菌,抗癌,神经保护,心脏保护,和保肝作用.虽然迷迭香通常被认为是安全的消费和局部应用,在一些个体中已经报道了过敏反应和皮炎。本文对迷迭香毒性的研究现状进行了深入的综述,阐明其潜在的不利影响和潜在机制。
    方法:谷歌学者,PubMed,Scopus,从这些数据库开始到2024年2月,WebofScience被用来进行广泛的研究。
    结果:所探讨的毒理学效应包括通过引起萎缩性和退行性改变影响肝脏和肾脏等器官,增加血尿素氮(BUN),天冬氨酸转氨酶(AST),降低总血清蛋白水平。迷迭香可能通过减少睾丸中的精子发生来诱导生殖毒性,睾丸激素,精子密度,和运动性。它还可能通过增加细胞质膜收缩来引发胎儿的遗传毒性和异常,凋亡体的形成,核小体间脱氧核糖核酸(DNA)片段,和DNA阶梯的形成。
    结论:虽然迷迭香被认为是安全的食品保存,由于对肾脏的潜在不利影响,因此对于慢性和高剂量应谨慎。肝脏,生殖系统,和畸胎学。此外,它强调了考虑药物相互作用的重要性。本文还强调了在现实暴露情况下考虑毒理学数据的重要性,并讨论了这些发现与人类健康的相关性。因此,建议进一步研究,以增强我们对迷迭香相关毒性特征的了解.
    BACKGROUND: Rosemary (Rosmarinus officinalis) contains alkaloids, phenolic acids, saponins, tannins, diterpenes, flavonoids, and essential oils and has antioxidant, anti-inflammatory, antibacterial, anticancer, neuroprotective, cardioprotective, and hepatoprotective effects. While rosemary is generally considered safe for consumption and topical application, allergic reactions and dermatitis have been reported in some individuals. This paper provides an in-depth review of the current studies on rosemary toxicity, shedding light on its potential adverse effects and underlying mechanisms.
    METHODS: Google Scholar, PubMed, Scopus, and Web of Science were used to perform extensive research from the inception of these databases until February 2024.
    RESULTS: The toxicological effects explored include affecting several organs such as the liver and kidney by causing atrophic and degenerative changes, increasing blood urea nitrogen (BUN), aspartate aminotransferase (AST), and reducing total serum protein levels. Rosemary may induce reproductive toxicity by decreasing spermatogenesis in the testes, testosterone, sperm density, and motility. It might also trigger genotoxicity and anomalies in fetuses by increasing cytoplasmic membrane shrinkage, the formation of apoptotic bodies, internucleosomal deoxyribonucleic acid (DNA) fragmentation, and DNA ladder formation.
    CONCLUSIONS: While rosemary is considered safe for food preservation, caution is warranted regarding chronic and high doses due to potential adverse effects on the kidneys, liver, reproductive system, and teratology. Additionally, it underscores the significance of considering drug interactions. The article also highlights the importance of considering toxicological data in realistic exposure situations and discusses the relevance of these findings for human health. Hence, further research is recommended to enhance our understanding of the toxicity profile associated with rosemary.
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  • 文章类型: Journal Article
    本系统综述(SR)旨在评估手稿,以帮助进一步阐明以下问题:微核测定(MA)是否也是牙龈中的有用标记,舌头,和评估体内细胞遗传学损伤的腭?通过电子数据库PubMed/Medline进行了搜索,Scopus,和WebofScience,截至2023年12月发表的所有研究。比较定义为标准化平均差(SMD),建立95%置信区间(CI)。在此设置中仔细选择和审查了34项研究的完整手稿。我们的结果表明,MA可能是体内牙龈组织损伤的有用生物标志物,这种组织可能是颊粘膜的有用替代品。荟萃分析分析不同的网站,而不考虑所研究的有害因素,颊粘膜(SMD=0.69,95%CI,-0.49至1.88,p=0.25)和牙龈(SMD=0.31,95%CI,-0.11至0.72,p=0.15),舌头显示出相似的结果和不同的结果(SMD=1.19,95%CI,0.47至1.91,p=0.001)。总之,我们的结论表明,MA可能是体内检测牙龈DNA损伤的有用标记,并且该组织可能是涂片的有效部位。
    The present systematic review (SR) aims to evaluate manuscripts in order to help further elucidate the following question: is the micronucleus assay (MA) also a useful marker in gingiva, tongue, and palate for evaluating cytogenetic damage in vivo? A search was performed through the electronic databases PubMed/Medline, Scopus, and Web of Science, all studies published up to December 2023. The comparisons were defined as standardized mean difference (SMD), and 95% confidence intervals (CIs) were established. Full manuscripts from 34 studies were carefully selected and reviewed in this setting. Our results demonstrate that the MA may be a useful biomarker of gingival tissue damage in vivo, and this tissue could be a useful alternative to the buccal mucosa. The meta-analysis analyzing the different sites regardless of the deleterious factor studied, the buccal mucosa (SMD = 0.69, 95% CI, - 0.49 to 1.88, p = 0.25) and gingiva (SMD = 0.31, 95% CI, - 0.11 to 0.72, p = 0.15), showed similar results and different outcome for the tongue (SMD = 1.19, 95% CI, 0.47 to 1.91, p = 0.001). In summary, our conclusion suggests that the MA can be a useful marker for detecting DNA damage in gingiva in vivo and that this tissue could be effective site for smearing.
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  • 文章类型: Journal Article
    中观浮游动物对维持海洋生态系统健康起着至关重要的作用,一些分类单元为监测环境和气候变化提供了生物学指标。最近,一些新出现的压力源被证明在某些方面影响海洋和沿海浮游动物。海洋生物基因组核心,紧密包装与高水平的完整性,可能会受到世界各地沿海地区人为活动的破坏,并影响其完整性。基因组完整性丧失导致食物链序列破坏的级联效应,从初级生产者到高级无脊椎动物。因此,使用关注遗传变化的生态毒理学方法监测基因组完整性损失似乎是一种合适的方法。文献综述表明,不同的应激源通过不同浓度和暴露时间的DNA损伤严重影响基因组完整性。受污染的沉积物也强烈影响河口和邻近沿海中游浮游动物群落的基因组完整性。
    Meso-zooplankton plays a vital role in maintaining healthy marine ecosystems, and some of the taxa provide biological indications for the monitoring of environmental and climate change. Recently, several newly emerging stressors were shown to impact marine and coastal meso-zooplankton in some ways. Marine organisms\' genomic core, tightly packed with high-level integrity, can be damaged by anthropogenic activities in coastal zones worldwide and impact their integrity. Genomic integrity loss leads to a cascade of effects on the destruction of the food chain sequences, from primary producers to higher invertebrates. Therefore, monitoring genomic integrity loss using ecotoxicological approaches that focus on genetic changes appears to be a suitable approach. A literature review shows that different stressors severely impact genomic integrity through DNA damage at different concentrations and exposure times. Contaminated sediments also strongly impact the genomic integrity of estuaries and adjacent coastal meso-zooplankton communities.
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  • 文章类型: Journal Article
    类固醇代表一类已知有助于许多疾病的激素(天然和合成)。尽管使用这些激素有上述有益效果,合成代谢-雄激素类固醇(AAS)也以非治疗方式被广泛滥用,用于增强肌肉和增加力量的特性,这可能导致不同组织的遗传毒性。本研究旨在了解遗传毒性是否可能是实验动物和人类研究中体内AAS暴露的合适生物标志物。发表在PubMed/Medline上的所有研究,Scopus,和WebofScience电子数据库提供了有关AAS引起的DNA损伤的数据进行了分析。本研究共纳入15篇文章,在彻底回顾研究后,共有8篇文章被归类为“坚强”,6人被归类为中度,只有1个被归类为“弱”,共有14项研究被认为是强的或中等的。这种分类使得可以认为目前的发现是可靠的。荟萃分析数据显示,与对照组相比,使用AAS的Wistar大鼠睾丸细胞在尾部长度和尾部DNA百分比方面存在统计学上的显着差异(p<0.001),因此,选定的文章被认为是同质的,I2为0%表示低异质性。总之,遗传毒性可以被认为是监测由于DNA断裂和氧化性DNA损伤而导致的AAS暴露的合适生物标志物。
    Steroids stand for a class of hormones (natural and synthetic) known to be helpful for a number of disorders. Despite the aforementioned beneficial effects of using these hormones, anabolic-androgenic steroids (AAS) are also widely abused in a non-therapeutic manner for muscle-building and strength-increasing properties that may lead to genotoxicity in different tissues. The present study aims to understand whether genotoxicity may be a suitable biomarker for AAS exposure in vivo in both experimental animal and human studies. All studies published in PubMed/Medline, Scopus, and Web of Science electronic databases that presented data on DNA damage caused by AAS were analyzed. A total of 15 articles were included in this study, and after thoroughly reviewing the studies, a total of 8 articles were classified as Strong, 6 were classified as Moderate, and only 1 was classified as Weak, totaling 14 studies being considered either Strong or Moderate. This classification makes it possible to consider the present findings as reliable. The meta-analysis data revealed a statistically significant difference in Wistar rat testis cells with AAS compared to control for tail length and % tail DNA (p < 0.001), so that the selected articles were considered homogeneous and the I2 of 0% indicated low heterogeneity. In summary, genotoxicity can be considered a suitable biomarker for monitoring AAS exposure as a result of DNA breakage and oxidative DNA damage.
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  • 文章类型: Journal Article
    N-亚硝基化合物的存在,特别是N-亚硝胺,在医药产品中,由于其显著的基因毒性和诱变作用,引起了全球的安全关注。这篇系统综述调查了它们在活性药物成分(API)中的毒性,药品,和药用辅料,以及新颖的检测分析策略,根本原因分析,重新制定战略,和亚硝胺的监管指南。这篇综述强调了N-亚硝基化合物的分子毒性,关注基因毒性,诱变,致癌,和其他生理效应。此外,它解决了持续的亚硝胺危机,开发不含亚硝胺的产品,以及灵敏的检测方法和精确的风险评估的重要性。这个全面的概述将帮助分子生物学家,分析科学家,研发部门的配方科学家,和研究人员参与管理亚硝胺诱导的毒性和促进更安全的药品。
    The presence of N-nitroso compounds, particularly N-nitrosamines, in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects. This systematic review investigates their toxicity in active pharmaceutical ingredients (APIs), drug products, and pharmaceutical excipients, along with novel analytical strategies for detection, root cause analysis, reformulation strategies, and regulatory guidelines for nitrosamines. This review emphasizes the molecular toxicity of N-nitroso compounds, focusing on genotoxic, mutagenic, carcinogenic, and other physiological effects. Additionally, it addresses the ongoing nitrosamine crisis, the development of nitrosamine-free products, and the importance of sensitive detection methods and precise risk evaluation. This comprehensive overview will aid molecular biologists, analytical scientists, formulation scientists in research and development sector, and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.
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  • 文章类型: Journal Article
    电子垃圾——大量电气和电子设备运入非洲的后果,尼日利亚从中获得了相当大的一部分,由已知对健康有害的成分组成。电子废物中一系列重金属(HMs)的组成可以追溯到许多健康状况,包括迄今为止尚未完全理解的癌症。这项研究协调了尼日利亚不同环境媒体中电子垃圾的HMs的主要数据,包括空气,土壤,表面灰尘,水和植物。我们估计了可能的健康影响,成人和儿童的单一和总体土壤和水污染指数,HM暴露后的致癌和非致癌风险,并绘制了可能的致癌机制。分析表明,土壤,水,尼日利亚环境中的表面粉尘和植物基质受到HMs的组合的不同但严重污染。水和表面粉尘基质的危害商和危害指数的显着高值表明非致癌风险对健康的不利影响。最高的HQ是铅和铬通过皮肤暴露于土壤和表面粉尘而产生的,尼日利亚儿童的平均值分别为1718.48、1146.14、1362.10和1794.61,其次是口腔暴露。这种观察模式与成人类别的观察模式相似。土壤中Pb和Cr引起的HI最高(分别为2.05E03和1.18E03),其次是表面粉尘。然而,这项研究表明,在污染环境中,儿童比成年人更容易受到健康威胁。致癌风险在尼日利亚环境中也遵循相同的表达模式。我们得出的结论是,暴露于电子垃圾会对致癌和非致癌健康造成重大风险,并提出毒性可能是通过DNA损伤介导的。尼日利亚环境中的氧化应激和炎症/免疫细胞功能障碍。
    E-waste -the aftermath of large amount of electrical and electronic equipment ferried into Africa from which Nigeria receives a significant chunk, is composed of components known to be hazardous to health. Composition of series of heavy metals (HMs) in e-waste is traceable to many health conditions including cancer which is hitherto incompletely understood. This study harmonizes primary data on HMs from e-waste in different Nigerian environmental media including the air, soil, surface dust, water and plant. We estimated the possible health implications, single and aggregative soil and water pollution indices both in adult and children categories, carcinogenic and non-carcinogenic risks secondary to HM exposure and mapped out the possible mechanism of carcinogenesis. Analysis showed that soil, water, surface dust and plant matrices in Nigerian environment are variedly but considerably contaminated with combination of HMs. The significantly high values of the hazard quotient and hazard index of both water and surface dust matrices are indicative of adverse health effect of the non-carcinogenic risk. The highest HQ is generated by Pb and Cr through dermal exposure to soil and surface dust with mean values of 1718.48, 1146.14, 1362.10 and 1794.61 respectively among Nigerian children followed by the oral exposure. This pattern of observation is similar to that obtained for adult category. HI due to Pb and Cr in soil constitutes the highest HI (2.05E+03 and 1.18E+03 respectively) followed by surface dust. However, this study precipitates the observation that children are more at health risk than adults in contaminated environment. Carcinogenic risk also follows the same pattern of expression in the Nigerian environment. We conclude that exposure to e-waste poses significant carcinogenic and non-carcinogenic health risks and the induction of toxicity may be mediated via DNA damage, oxidative stress and inflammatory/immune cells dysfunction in Nigerian environment.
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