Chromosomal aberrations

染色体畸变
  • 文章类型: Meta-Analysis
    现有文献表明,慢性镉(Cd)暴露与DNA损伤和遗传毒性的诱导之间存在关联。然而,个别研究的观察结果不一致且相互矛盾。因此,当前的系统评价旨在从现有文献中收集证据,以综合定量和定性证实遗传毒性标记与职业性Cd暴露人群之间的关联。经过系统的文献检索,选择了评估职业暴露于Cd和未暴露的工人中DNA损伤标记的研究。包括的DNA损伤标记是染色体畸变(染色体,染色单体,姐妹染色单体交换),单核细胞和双核细胞中的微核(MN)频率(具有凝聚染色质,浅裂核,核芽,有丝分裂指数,核质桥,固缩症,和karyorrhexis),彗星测定(尾巴强度,尾部长度,尾矩,和橄榄尾巴时刻),和氧化DNA损伤(8-羟基脱氧鸟苷)。使用随机效应模型汇集平均差异或标准化平均差异。采用Cochran-Q检验和I2统计量监测纳入研究的异质性。审查中包括了29项研究,其中3080名职业暴露于Cd和1807名未暴露的工人。暴露组的血液[4.77μg/L(-4.94-14.48)]和尿液样本[标准化平均差0.47(0.10-0.85)]中的Cd高于暴露组。Cd暴露与以MN频率增加为特征的较高水平的DNA损伤呈正相关[7.35(-0.32-15.02)],姐妹染色单体交换[20.30(4.34-36.26)],染色体畸变,和氧化DNA损伤(彗星试验和8OHdG[0.41(0.20-0.63)])相比未暴露。然而,具有相当大的研究间异质性。慢性Cd暴露与DNA损伤增强有关。然而,更广泛的纵向研究与足够的样本量是必要的,以协助目前的观察和促进理解Cd在诱导DNA损伤的作用。Prospero注册ID:CRD42022348874。
    Existing literature suggests an association between chronic cadmium (Cd) exposure and the induction of DNA damage and genotoxicity. However, observations from individual studies are inconsistent and conflicting. Therefore current systematic review aimed to pool evidence from existing literature to synthesize quantitative and qualitative corroboration on the association between markers of genotoxicity and occupational Cd exposed population. Studies that evaluated markers of DNA damage among occupationally Cd-exposed and unexposed workers were selected after a systematic literature search. The DNA damage markers included were chromosomal aberrations (chromosomal, chromatid, sister chromatid exchange), Micronucleus (MN) frequency in mono and binucleated cells (MN with condensed chromatin, lobed nucleus, nuclear buds, mitotic index, nucleoplasmatic bridges, pyknosis, and karyorrhexis), comet assay (tail intensity, tail length, tail moment, and olive tail moment), and oxidative DNA damage (8-hydroxy-deoxyguanosine). Mean differences or standardized mean differences were pooled using a random-effects model. The Cochran-Q test and I2 statistic were used to monitor heterogeneity among included studies. Twenty-nine studies with 3080 occupationally Cd-exposed and 1807 unexposed workers were included in the review. Cd among the exposed group was higher in blood [4.77 μg/L (-4.94-14.48)] and urine samples [standardized mean difference 0.47 (0.10-0.85)] than in the exposed group. The Cd exposure is positively associated with higher levels of DNA damage characterized by increased frequency of MN [7.35 (-0.32-15.02)], sister chromatid exchange [20.30 (4.34-36.26)], chromosomal aberrations, and oxidative DNA damage (comet assay and 8OHdG [0.41 (0.20-0.63)]) compared to the unexposed. However, with considerable between-study heterogeneity. Chronic Cd exposure is associated with augmented DNA damage. However, more extensive longitudinal studies with adequate sample sizes are necessary to assist the current observations and promote comprehension of the Cd\'s role in inducing DNA damage.Prospero Registration ID: CRD42022348874.
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  • 文章类型: Journal Article
    研究表明,长期铅(Pb)暴露可能会引起脱氧核糖核酸(DNA)损伤。然而,这方面没有综合证据。我们系统地回顾了现有文献,并综合了有关慢性铅暴露与遗传毒性标记之间关联的证据。从PubMed系统搜索了报告职业铅暴露和未暴露对照中DNA损伤生物标志物的观察性研究,Scopus和Embase数据库从成立到2022年1月。包括的标志物是微核频率(MN),染色体畸变,彗星试验,和8-羟基脱氧鸟苷。在本审查执行期间,我们遵循系统评价和荟萃分析(PRISMA)指南的首选报告项目。使用随机效应模型汇总了铅暴露组和对照组之间DNA损伤生物学标记的平均差异。使用Cochran-Q检验和I2统计量评估异质性。该综述包括45项研究,比较了铅暴露和未暴露之间的DNA损伤标记。主要研究利用口腔和/或外周白细胞来评估DNA损伤。汇总的定量结果显示,以MN和SCE频率增加为特征的DNA损伤明显更高,染色体畸变,和氧化DNA损伤(彗星试验和8-OHdG)中铅暴露者比未暴露者。然而,纳入综述的研究在研究中表现出高水平的异质性.慢性铅暴露与DNA损伤有关。然而,高品质,需要进行多中心研究,以加强目前的观察,并进一步了解铅在诱导DNA损伤中的作用。CRD42022286810。
    Studies suggest that chronic lead (Pb) exposure may induce deoxyribonucleic acid (DNA) damage. However, there is no synthesised evidence in this regard. We systematically reviewed existing literature and synthesised evidence on the association between chronic Pb exposure and markers of genotoxicity. Observational studies reporting biomarkers of DNA damage among occupationally Pb-exposed and unexposed controls were systematically searched from PubMed, Scopus and Embase databases from inception to January 2022. The markers included were micronucleus frequency (MN), chromosomal aberrations, comet assay, and 8-hydroxy-deoxyguanosine. During the execution of this review, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Mean differences in the biological markers of DNA damage between Pb-exposed and control groups were pooled using the random-effects model. The heterogeneity was assessed using the Cochran-Q test and I2 statistic. The review included forty-five studies comparing markers of DNA damage between Pb-exposed and unexposed. The primary studies utilised buccal and/or peripheral leukocytes for evaluating the DNA damage. The pooled quantitative results revealed significantly higher DNA damage characterised by increased levels of MN and SCE frequency, chromosomal aberrations, and oxidative DNA damage (comet assay and 8-OHdG) among Pb-exposed than the unexposed. However, studies included in the review exhibited high levels of heterogeneity among the studies. Chronic Pb exposure is associated with DNA damage. However, high-quality, multicentred studies are required to strengthen present observations and further understand the Pb\'s role in inducing DNA damage. CRD42022286810.
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  • 文章类型: Journal Article
    除了迄今为止三次审查的部分报道(1994年、2009年、2019年),没有使用最常用的基因毒性测定法对汞(Hg)和人类暴露的基因毒性研究进行审查:姐妹染色单体交换(SCE),染色体畸变(CA),细胞松弛素B阻断微核试验(CBMN),和单细胞凝胶电泳(SCGE或碱性彗星测定)。从第一次汞基因毒性研究开始到《水50%公约》生效五十年,汞及其衍生物的遗传毒性潜力仍然存在争议。考虑到这些先例,我们介绍了有关汞和人类暴露的基因毒性研究的第一个系统文献概述,这些研究使用了标准的基因毒性测定法。迄今为止,汞人类致癌物分类没有足够的证据,所以新的数据收集可以有很大的帮助。对有关基因毒性测定和离体人体样品暴露的科学文献中可用的研究(在2021年10月底之前在PubMed或WebofScience上以英语或西班牙语发表的研究)进行了综述,在体内,和体外。提供了总共66篇文章的结果。有机(o)汞化合物比无机和/或元素化合物毒性更大,不排除所有代表风险。在偶然暴露的人群中研究最多的无机(i)汞化合物,职业,或者医源性,和/或在人类细胞中,是氯化汞和硝酸汞以及有机化合物,是甲基汞,硫柳汞,氯化甲基汞,乙酸苯汞,和氢氧化甲基汞.
    Beside partial coverage in three reviews so far (1994, 2009, 2019), there is no review on genotoxic studies dealing with mercury (Hg) and human exposure using the most usual genotoxic assays: sister chromatid exchanges (SCE), chromosomal aberrations (CA), cytochalasin B blocked micronucleus assay (CBMN), and single-cell gel electrophoresis (SCGE or alkaline comet assay). Fifty years from the first Hg genotoxicity study and with the Minamata Convention in force, the genotoxic potential of Hg and its derivatives is still controversial. Considering these antecedents, we present this first systematic literature overview of genotoxic studies dealing with Hg and human exposure that used the standard genotoxic assays. To date, there is not sufficient evidence for Hg human carcinogen classification, so the new data collections can be of great help. A review was made of the studies available (those published before the end of October 2021 on PubMed or Web of Science in English or Spanish language) in the scientific literature dealing with genotoxic assays and human sample exposure ex vivo, in vivo, and in vitro. Results from a total of 66 articles selected are presented. Organic (o)Hg compounds were more toxic than inorganic and/or elemental ones, without ruling out that all represent a risk. The most studied inorganic (i)Hg compounds in populations exposed accidentally, occupationally, or iatrogenically, and/or in human cells, were Hg chloride and Hg nitrate and of the organic compounds, were methylmercury, thimerosal, methylmercury chloride, phenylmercuric acetate, and methylmercury hydroxide.
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  • 文章类型: Journal Article
    硼,通常以硼酸的形式,被广泛用作绝缘产品的阻燃剂,尽管人类通过食物摄取硼,高暴露可能导致不必要的健康影响。我们评估了硼酸的毒性,硼砂和其他形式的硼,吸入后,皮肤和口腔暴露。口腔暴露后,硼被胃肠道吸收。完整的皮肤似乎比受损的皮肤对硼构成更有效的屏障。硼排泄似乎主要通过尿液发生,尽管皮肤暴露后,胆汁和胃肠道内容物中已显示出硼。吸入毒性数据很少,但是一项动物研究表明,吸入硼酸含量为20%的纤维素后胎儿体重降低。在某些情况下,皮肤暴露于硼酸已被证明是致命的,毒性作用的范围包括腹部以及对皮肤的局部作用。硼酸的死亡也发生在口服摄入后,动物的终点是体重减轻和生殖毒性。关于遗传毒性研究,总体情况表明含硼化合物没有遗传毒性。在一项为期2年的小鼠研究中,没有证据表明硼酸具有致癌性。
    Boron, often in the form of boric acid, is widely used as a flame retardant in insulation products, and although humans ingest boron through food, high exposure may lead to unwanted health effects. We assessed the toxicity of boric acid, borax and other forms of boron, after inhalation, dermal and oral exposure. After oral exposure, boron is absorbed over the gastrointestinal tract. Intact skin seems to pose a more effective barrier to boron than compromised skin. Boron excretion seems to mainly occur via the urine, although after skin exposure boron has been demonstrated in bile and gastrointestinal contents. Inhalation toxicity data are sparse, but one animal study showed reduced foetal weight after inhalation of cellulose that had a boric acid content of 20%. Skin exposure to boric acid has proven fatal in some cases, and the range of toxicity effects include abdominal as well as local effects on the skin. Fatalities from boric acid also have occurred after oral ingestion, and the endpoints in animals are weight loss and reproductive toxicity. Concerning genotoxicity studies, the overall picture indicates that boron-containing compounds are not genotoxic. There was no evidence of the carcinogenicity of boric acid in a 2-year study in mice.
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  • 文章类型: Journal Article
    BACKGROUND: Delayed parenthood, by both women and men, has become more common in developed countries. The adverse effect of advanced maternal age on embryo aneuploidy and reproductive outcomes is well known. However, whether there is an association between paternal age (PA) and embryonic chromosomal aberrations remains controversial. Oocyte donation (OD) is often utilized to minimize maternal age effects on oocyte and embryo aneuploidy, thus providing an optimal model to assess the effect of PA. Several studies have revealed a higher than expected rate of aneuploidy in embryos derived from young oocyte donors, which warrants examination as to whether this may be attributed to advanced PA (APA).
    UNASSIGNED: The objective of this systematic review and individual patient data (IPD) meta-analysis is to evaluate existing evidence regarding an association between PA and chromosomal aberrations in an OD model.
    METHODS: This review was conducted according to PRISMA guidelines for systematic reviews and meta-analyses. Medline, Embase and Cochrane databases were searched from inception through March 2020 using the (MeSH) terms: chromosome aberrations, preimplantation genetic screening and IVF. Original research articles, reporting on the types and/or frequency of chromosomal aberrations in embryos derived from donor oocytes, including data regarding PA, were included. Studies reporting results of IVF cycles using only autologous oocytes were excluded. Quality appraisal of included studies was conducted independently by two reviewers using a modified Newcastle-Ottawa Assessment Scale. A one-stage IPD meta-analysis was performed to evaluate whether an association exists between PA and aneuploidy. Meta-analysis was performed using a generalized linear mixed model to account for clustering of embryos within patients and clustering of patients within studies.
    RESULTS: The search identified 13 032 references, independently screened by 2 reviewers, yielding 6 studies encompassing a total of 2637 IVF-OD cycles (n = 20 024 embryos). Two \'low\' quality studies using FISH to screen 12 chromosomes on Day 3 embryos (n = 649) reported higher total aneuploidy rates and specifically higher rates of trisomy 21, 18 and 13 in men ≥50 years. One \'moderate\' and three \'high\' quality studies, which used 24-chromosome screening, found no association between PA and aneuploidy in Day 5/6 embryos (n = 12 559). The IPD meta-analysis, which included three \'high\' quality studies (n = 10 830 Day 5/6 embryos), found no significant effect of PA on the rate of aneuploidy (odds ratio (OR) 0.97 per decade of age, 95% CI 0.91-1.03), which was robust to sensitivity analyses. There was no association between PA and individual chromosome aneuploidy or segmental aberrations, including for chromosomes X and Y (OR 1.06 per decade of age, 95% CI 0.92-1.21). Monosomy was most frequent for chromosome 16 (217/10802, 2.01%, 95% CI 1.76-2.29%) and trisomy was also most frequent for chromosome 16 (194/10802, 1.80%, 95% CI 1.56-2.06%).
    UNASSIGNED: We conclude, based on the available evidence, that APA is not associated with higher rates of aneuploidy in embryos derived from OD. These results will help fertility practitioners when providing preconception counselling, particularly to older men who desire to have a child.
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  • 文章类型: Journal Article
    The percentage of people affected by overweight, obesity and/or diabetes drastically increased within the last decades. This development is still ongoing, which puts a large part of our society at increased risk for diseases, such as cancer, cardiovascular diseases and cognitive impairment. Especially the development of type 2 diabetes and overweight/obesity could theoretically be prevented. The loss of DNA and genome stability is associated with the above-mentioned metabolic diseases. Insulin resistance, high blood glucose levels or increased body fat are linked to a chronically elevated inflammatory state. This amplifies oxidative stress, might lead to oxidative DNA damage, impairs the cellular proliferation process and results in mutations; all of which increase the possibility for the development of dysfunctional cells, tissue and organs. An established method to measure chromosomal damage is the cytokinesis block micronucleus (CBMN) cytome assay. The aim of this systematic review and meta-analysis is to collect and analyse the current literature of diabetic, obese and overweight patients and their link to cellular mutations measured by the CBMN assay. A clear trend towards increased genome damage in these metabolic diseases was observed. Significantly increased frequencies of chromosomal aberrations were seen in type 2 diabetic subjects (micronuclei frequency: SMD: 1.18, 95% CI: 0.76, 1.60; I2 = 84%). In both, type 1 and type 2 diabetics, disease progression as well as medical quality and quantity were linked to further elevated genome instability. In type 1 diabetic and overweight/obese subjects the number of studies is small and for valid and reliable results more data are needed. Besides the traditionally used material for this method, PBMCs, we extended our analysis to buccal cells in order to qualitatively compare the two cell types. Finally, we discuss knowledge as well as technical/methodical gaps of the CBMN cytome assay and its usability for clinical practice in these metabolic diseases.
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  • 文章类型: Journal Article
    To examine the risk for chromosomal aberrations in fetuses of colchicine-treated patients in a large cohort, and to perform a systematic literature review on the subject.
    For the observational study, a retrospective search was performed through the Ministry of Health computerized database, for all invasive tests performed due to parental colchicine treatment over the years 2003-19. The rate of aberrant karyotypes in pregnancies exposed to colchicine was compared with a local cohort of 2752 normal pregnancies, yielding six (0.2%) karyotype-detectable findings. In addition, a systematic literature search was conducted for studies examining the rate of chromosomal aberrations in pregnancies exposed to colchicine.
    The study group consisted of 755 pregnancies karyotyped due to colchicine exposure. A marked decrease due to this indication was noted over the years (i.e. 67 cases in 2003 vs 8 in 2019). Five (0.66%) chromosomal aberrations were noted: 47,XXY; 45,X0; 47,XYY; and two fetuses with trisomy 21. This rate was significantly increased compared with the control population [relative risk 2.2 (95% CI: 1.1, 4.2)]. Literature search yielded four studies encompassing 740 pregnancies. The rate of chromosomal aberrations ranged from \'none\' (in three studies) up to 1.5%. Quality assessment of the evidence was defined as \'low\'.
    The results of our observational study support the concern that colchicine treatment is associated with increased risk for fetal chromosomal aberrations; however, the absolute risk is relatively low (one in 151 pregnancies). This information should be taken into account when considering invasive testing in such pregnancies.
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  • 文章类型: Journal Article
    Objective To explore the risk for abnormal chromosomal microarray analysis (CMA) findings in pregnancies with oligohydramnios. Methods Data from all CMA analyses performed due to oligohydramnios between 2013 and 2017 were retrospectively obtained from the Israeli Ministry of Health database. The rate of clinically significant (pathogenic and likely pathogenic) findings was compared to a local cohort of pregnancies with normal ultrasound, yielding a 1.4% rate of abnormal CMA results. In addition, a search was conducted through the PubMed database addressing the issue. Results Fifty CMA analyses were performed due to oligohydramnios. The 2% risk for clinically significant CMA finding in pregnancies with oligohydramnios did not differ from the control population of 5541 pregnancies with normal ultrasound - relative risk (RR) 1.4 [95% confidence interval (CI) 0.2-10.2]. Literature search yielded 394 titles, of which four relevant articles were selected, all using fetal karyotyping. Conclusion There is yet insufficient evidence to support invasive prenatal testing in pregnancies with isolated oligohydramnios.
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  • 文章类型: Journal Article
    Traditional Medicine/Complementary and Alternative Medicine is a practice that incorporates medicine based on plants, animals, and minerals for diagnosing, treating, and preventing certain diseases, including chronic degenerative diseases such as obesity, diabetes, hypertension, atherosclerosis, and cancer. Different factors generate its continued acceptance, highlighting its diversity, easy access, low cost, and the presence of relatively few adverse effects and, importantly, a high possibility of discovering antigenotoxic agents. In this regard, it is known that the use of different antigenotoxic agents is an efficient alternative to preventing human cancer and that, in general, these can act by means of a combination of various mechanisms of action and against one or various mutagens and/or carcinogens. Therefore, it is relevant to confirm its usefulness, efficacy, and its spectrum of action through different assays. With this in mind, the present manuscript has as its objective the compilation of different investigations carried out with garlic that have demonstrated its genoprotective capacity, and that have been evaluated by means of five of the most outstanding tests (Ames test, sister chromatid exchange, chromosomal aberrations, micronucleus, and comet assay). Thus, we intend to provide information and bibliographic support to investigators in order for them to broaden their studies on the antigenotoxic spectrum of action of this perennial plant.
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  • 文章类型: Journal Article
    Cytogenetic examination and the detection of chromosomal aberrations in chronic lymphocytic leukemia (CLL) is an integral part of prognostic stratification and treatment decisions. Improvements in cytogenetic methods, notably the introduction of the cell stimulation method, have led to the detection of chromosomal aberrations in 80% of CLL cases. A comprehensive analysis of cytogenetic aberrations recently showed that complex karyotypes (CKs) defined as the detection of either three or more or five or more chromosomal changes in a karyotype have a poor prognostic impact. The current efforts at the international level are focused on the goal of including CK assessment among prognostic markers for CLL patients at diagnosis as well as after treatment. This review of the literature documents the clinical importance of CK findings in CLL and the necessity of including this factor in other poor prognostic indicators.
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