砷对DNA甲基化影响的研究进展

砷污染是全球性的问题,砷暴露与多种疾病密切相关,并能诱发癌症。细胞实验、动物模型实验和流行病学研究表明,砷暴露会影响全基因组DNA甲基化水平;另外,砷暴露也被证实会导致原癌基因和抑癌基因等多种基因启动子的甲基化异常。砷暴露干扰DNA甲基化的作用机制非常复杂。砷可能通过砷甲基化与DNA甲基化过程的耦合改变DNA甲基化状态,也可能通过调节DNA甲基化转移酶(DNMTs)的活力或通过氧化应激效应干扰DNA去甲基化来影响DNA甲基化状态。虽然最终的作用机制尚不明确,但是目前的DNA表观基因毒理学研究为砷暴露的环境健康研究提供了新视角。该文就砷对全基因组和特定基因启动子甲基化的影响及其分子作用机制进行综述。     

DNA甲基化与食管癌的相关研究进展

目前的研究表明,除基因突变或缺失外,表观遗传改变是肿瘤发生发展的另一重要原因。DNA甲基化是影响表观遗传的重要机制之一,其在基因表观遗传调控中起重要作用。研究表明,DNA甲基化在食管癌的发生中起重要作用,并可能作为食管癌早期诊断标记物。     

电离辐射致DNA甲基化的研究进展

电离辐射是一种广泛存在于环境中的危害因素,不仅存在于自然环境中,随着工业和医学上的应用,人们接触电离辐射的机会也越来越多。电离辐射不仅直接导致细胞损伤,也具有遗传毒性,可引起多种远后效应,包括基因不稳定性、辐射致癌等。表观遗传可以调节基因活性和表达,而DNA甲基化是研究较多的表观遗传修饰方式,DNA甲基化在电离辐射所致损伤中也发挥着作用。从电离辐射与基因组甲基化、与重复序列DNA甲基化、与特定基因甲基化,以及电离辐射致甲基化改变的可能机制等方面,综述了电离辐射对DNA甲基化的影响及可能的作用机制。     

071 基于PCR技术的DNA甲基化检测方法研究进展

DNA甲基化是表观遗传修饰最基本的方式,在维持正常细胞功能、胚胎发育和肿瘤发生中起着重要的作用,是当前学术研究的重点和热点.随着研究的深入,为满足不同研究目的需求,DNA甲基化检测方法也得到了较快的发展.本文针对近年来基于PCR技术的DNA甲基化检测方法进行简要的分析总结,为选择适合研究目的的检测方法提供帮助.     

基于PCR技术的DNA甲基化检测方法研究进展

DNA甲基化是表观遗传修饰最基本的方式，在维持正常细胞功能、胚胎发育和肿瘤发生中起着重要的作用，是当前学术研究的重点和热点。随着研究的深入，为满足不同研究目的需求，DNA甲基化检测方法也得到了较快的发展。本文针对近年来基于PCR技术的DNA甲基化检测方法进行简要的分析总结，为选择适合研究目的的检测方法提供帮助。     

异常DNA甲基化与复发性流产关系的研究进展

复发性流产（recurrent spontaneous abortion,RSA）是生殖育龄期女性的常见疾病,其发病机制尚不完全清楚。近年来,随着表观遗传学领域的深入研究,DNA甲基化逐渐成为RSA病理生理机制的新视角。研究表明,DNA甲基化修饰调控与RSA密切相关,DNA甲基化异常及其引起的印迹障碍、蜕膜相关基因表达...     

DNA甲基化在肺癌早期诊断中的研究进展

目的：通过文献综述分析DNA甲基化在肺癌早期诊断中的研究方法和应用方向。方法：共计阅读50篇与DNA甲基化相关的科研论文,对文献中提到的研究方法、研究类型以及研究结果进行了归纳分析,最后将具有代表性的研究结果作为本文的引用内容。结果：抑癌基因的启动子甲基化研究是目前肺癌早期诊断的主要研究方法,并在肺组织、外周血、肺泡灌洗液等标本的监测中表现出巨大的应用潜力。结论：DNA甲基化的样本检测技术虽然已经获得了大量的研究成果,但仍然存在灵敏度低、获取困难等问题急需解决,本文的一系列综述对后期的研究具有一定的参考意义。     

DNA甲基化在毒理学中的应用前景

许多物理或化学因子具有潜在的对基因组引起不利的遗传变化,导致基因型遗传上的不利改变,通常认为会导致突变的结果.然而,致突变作用并不是遗传改变的唯一机制,表观遗传基础对此也具有重要作用.DNA甲基化成为外遗传的基础机制已经倍受关注.基于甲基化异常与疾病之间的关系及近年毒物对DNA甲基化研究的基础,我们指出DNA甲基化改变在许多化学物毒性中起重要的作用,DNA甲基化状态评价对于全部安全性评价具有重要应用前景.     

慢性砷暴露与DNA甲基化研究进展

砷是一种广泛存在于自然环境中的具有致癌作用的非金属物质。慢性砷暴露会造成全身多器官损伤,因其发病机制不明确、缺乏特效药及早期生物学标志物等因素,长期以来成为科技工作者研究的重点和热点。表观遗传修饰不仅与砷暴露存在相关性,而且可通过调控关键分子的表达参与砷诱导的早期损伤,成为砷暴露机制研究的重要方向。DNA甲基化作为表观...     

Influence of Prenatal Lead Exposure on Genomic Methylation of Cord Blood DNA

Background

Fetal lead exposure is associated with adverse pregnancy outcomes and developmental and cognitive deficits; however, the mechanism(s) by which lead-induced toxicity occurs remains unknown. Epigenetic fetal programming via DNA methylation may provide a pathway by which environmental lead exposure can influence disease susceptibility.

Objective

This study was designed to determine whether prenatal lead exposure is associated with alterations in genomic methylation of leukocyte DNA levels from umbilical cord samples.

Methods

We measured genomic DNA methylation, as assessed by Alu and LINE-1 (long interspersed nuclear element-1) methylation via pyrosequencing, on 103 umbilical cord blood samples from the biorepository of the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) study group. Prenatal lead exposure had been assessed by measuring maternal bone lead levels at the mid-tibial shaft and the patella using a spot-source ¹⁰⁹Cd K-shell X-ray fluorescence instrument.

Results

We found an inverse dose–response relationship in which quartiles of patella lead correlated with cord LINE-1 methylation (p for trend = 0.01) and and tibia lead correlated with Alu methylation (p for trend = 0.05). In mixed effects regression models, maternal tibia lead was negatively associated with umbilical cord genomic DNA methylation of Alu (β= −0.027; p = 0.01). We found no associations between cord blood lead and cord genomic DNA methylation.

Conclusions

Prenatal lead exposure is inversely associated with genomic DNA methylation in cord blood. These data suggest that the epigenome of the developing fetus can be influenced by maternal cumulative lead burden, which may influence long-term epigenetic programming and disease susceptibility throughout the life course.     

地下空间空气环境影响因素分析

分析了地下空间温湿度特性,以及放射性污染、微生物、有害气体、固体颗粒物等地下空间空气环境的影响因素,因地制宜采取防潮、通风、除尘、杀菌消毒等措施是改善地下空气环境的有效途径,独立除湿技术、增加空气负离子也是提高空气品质的有效措施。     

DNA甲基化在复发性流产病因中的研究进展

复发性流产（recurrent spontaneous abortion,RSA）是一种常见病理性妊娠,其中有约50%的患者病因和发病机制不明确。随着表观遗传学研究领域的发展,尤其是近年来DNA甲基化的研究,为RSA的病理生理机制提供了一个新视角。研究发现,基因DNA甲基化的功能缺陷、DNA的甲基化修饰调控及DNA甲基化介导的其他表观遗传修饰方式与RSA密切相关,印迹基因DNA甲基化、胎盘特有基因DNA甲基化以及精子DNA甲基化异常都直接或间接地影响胚胎的着床、生长及发育过程,最终导致RSA的发生。现阐述DNA甲基化在RSA发生、发展中的作用及其研究进展。     

DNA甲基化在卵巢癌中的研究进展

卵巢癌是妇科常见恶性肿瘤之一,病死率居妇科肿瘤之首.因早期多无明显症状体征且缺乏敏感和特异的筛选手段,70％以上的患者发现时已为晚期,多伴有腹水、盆腹腔广泛转移,恶性程度高,预后极差,故卵巢癌的早发现早诊断在提高生存率方面显得尤为重要.近年表观遗传学的研究进展迅速,在卵巢癌发生发展治疗等方面具有重要的指导意义,为卵巢癌的早期诊断、优化治疗、改善预后指明新方向.DNA甲基化是最常见也是目前研究最清楚的表观遗传修饰形式,能引起染色质结构、DNA构象、DNA稳定性及DNA与蛋白质相互作用方式的改变,调控基因表达,在肿瘤的发生发展中扮演重要角色.就DNA甲基化在卵巢癌表观遗传学中的研究进展作一综述.     

辅助生殖技术与胚胎DNA甲基化

表观遗传修饰,尤其DNA甲基化在控制细胞表达中发挥重要作用。高甲基化的DNA与基因沉默有关,低甲基化的DNA可以激活基因的转录,哺乳动物中70%~80%的Cp G位点被甲基化。DNA的甲基化状态并不像基因组那样稳定,在原始生殖细胞(primordial germ cells,PGCs)和早期胚胎阶段发生了一系列重组,即甲基化模式擦除、甲基化模式重新建立和甲基化模式维持。发达国家通过辅助生殖技术(assisted reproductive technology,ART)出生的婴儿已占1%~3%,并不断增长。ART方案的多样性和基因组印迹疾病的罕见性导致ART过程与印迹障碍发病率间的因果关系复杂化。除早产的发生率增加外,ART过程可导致配子及胚胎发生异常的表观遗传修饰和重组。脐疝-巨舌-巨体综合征(Beckwith-Wiedemann syndrome,BWS)、普达-威利综合征(Prader-Willi syndrome,PWS)等均为最具有代表性的基因组印迹疾病。     

Arsenic Exposure and DNA Methylation Among Elderly Men

BACKGROUND:: Arsenic exposure has been linked to epigenetic modifications such as DNA methylation in in-vitro and animal studies. This association has also been explored in highly exposed human populations, but studies among populations environmentally exposed to low arsenic levels are lacking. METHODS:: We evaluated the association between exposure to arsenic, measured in toenails, and blood DNA methylation in Alu and Long Interspersed Nucleotide Element-1 (LINE-1) repetitive elements in elderly men environmentally exposed to low levels of arsenic. We also explored potential effect modification by plasma folate, cobalamin (vitamin B12), and pyridoxine (vitamin B6). The study population was 581 participants from the Normative Aging Study in Boston, of whom 434, 140, and 7 had 1, 2, and 3 visits, respectively, between 1999-2002 and 2006-2007. We used mixed-effects models and included interaction terms to assess potential effect modification by nutritional factors. RESULTS:: There was a trend of increasing Alu and decreasing LINE-1 DNA methylation as arsenic exposure increased. In subjects with plasma folate below the median (<14.1 ng/mL), arsenic was positively associated with Alu DNA methylation (β = 0.08 [95% confidence interval = 0.03 to 0.13] for one interquartile range [0.06 μg/g] increase in arsenic), whereas a negative association was observed in subjects with plasma folate above the median (β = -0.08 [-0.17 to 0.01]). CONCLUSIONS:: We found an association between arsenic exposure and DNA methylation in Alu repetitive elements that varied by folate level. This suggests a potential role for nutritional factors in arsenic toxicity.     

家庭因素对儿童肥胖治疗的影响

目的 为了解家庭因素对儿童肥胖治疗的影响。方法 对一组接受家庭行为疗法三年的肥胖我简格家庭环境因素进行了分析。 结果 治疗有效组肥胖度平均下降１４．６％,治疗无效组肥胖度平均上升５．３％。无效组中,家长不爱运动、对孩子减肥意见不一致者所占比例较高;有效组中,家长督促孩子运动、参与减肥方案、限制购买高热卡食物者明显高于无效组。 结论 家庭因素在儿童肥胖治疗中起着至关重要的作用,若要获得良好的减肥效果     

Biomarkers of Lead Exposure and DNA Methylation within Retrotransposons

Background

DNA methylation is an epigenetic mark that regulates gene expression. Changes in DNA methylation within white blood cells may result from cumulative exposure to environmental metals such as lead. Bone lead, a marker of cumulative exposure, may therefore better predict DNA methylation than does blood lead.

Objective

In this study we compared associations between lead biomarkers and DNA methylation.

Methods

We measured global methylation in participants of the Normative Aging Study (all men) who had archived DNA samples. We measured patella and tibia lead levels by K-X-Ray fluorescence and blood lead by atomic absorption spectrophotometry. DNA samples from blood were used to determine global methylation averages within CpG islands of long interspersed nuclear elements-1 (LINE-1) and Alu retrotransposons. A mixed-effects model using repeated measures of Alu or LINE-1 as the dependent variable and blood/bone lead (tibia or patella in separate models) as the primary exposure marker was fit to the data.

Results

Overall mean global methylation (± SD) was 26.3 ± 1.0 as measured by Alu and 76.8 ± 1.9 as measured by LINE-1. In the mixed-effects model, patella lead levels were inversely associated with LINE-1 (β = −0.25; p < 0.01) but not Alu (β = −0.03; p = 0.4). Tibia lead and blood lead did not predict global methylation for either Alu or LINE-1.

Conclusion

Patella lead levels predicted reduced global DNA methylation within LINE-1 elements. The association between lead exposure and LINE-1 DNA methylation may have implications for the mechanisms of action of lead on health outcomes, and also suggests that changes in DNA methylation may represent a biomarker of past lead exposure.