DNA损伤和修复在肝癌中的研究进展

人体细胞中DNA损伤后会引起细胞一系列反应,主要包括损伤信号的传导、损伤与修复、诱导细胞死亡等.肝癌的发生正是由于这些诱因同时作用于损伤修复系统的某个环节,使DNA损伤不能修复或不能正确修复,从而使肝细胞发生恶性转化,最后导致肝癌的发生.因此,损伤DNA的累积则成为肝癌发生的重要分子机制,对其深入研究将会为肝癌的治疗奠定基础.该文通过查阅相关文献,综述近年来DNA损伤和修复在肝癌中的研究进展.     

DNA修复相关基因启动子甲基化和肿瘤化疗耐药的进展

肿瘤细胞DNA修复能力与化疗药物敏感性密切相关,而DNA启动子甲基化可导致DNA修复相关基因转录失活、基因沉默、蛋白表达量改变等影响DNA的修复能力,继而导致肿瘤对化疗药物的固有性或获得性耐药。该文着重阐述DNA修复相关基因O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)、人类mut1同源物(hMLH1)和范科尼贫血互补基团F(FANCF)启动子甲基化与肿瘤化疗耐药之间的关系。     

DNA修复相关基因启动子甲基化和肿瘤化疗耐药的进展

肿瘤细胞DNA修复能力与化疗药物敏感性密切相关,而DNA启动子甲基化可导致DNA修复相关基因转录失活、基因沉默、蛋白表达量改变等影响DNA的修复能力,继而导致肿瘤对化疗药物的固有性或获得性耐药。该文着重阐述DNA修复相关基因O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）、人类mut1同源物（hMLH1）和范科尼贫血互补基团F （FANCF）启动子甲基化与肿瘤化疗耐药之间的关系。     

缺氧的血清剥夺诱导的PC12细胞DNA损伤与修复

探讨PC12细胞在缺氧(37℃,5%O2,95%N2)、血清剥夺条件下DNA损伤与修复、凋亡、坏死或生存的变化规律.应用单细胞凝胶电泳技术、流式细胞学技术检测在不同时间点,缺氧、无血清培养等诱导下对PC12细胞单链DNA损伤与修复、凋亡的影响.结果发现在PC12细胞DNA损伤值均在0.5h时达第一个峰值,随后下降.3h后DNA损伤数值再次逐渐增加并达到最高值.细胞凋亡峰值略滞后于DNA损伤峰值,并于DNA损伤程度基本相平行.提示PC12细胞在缺氧和血清剥夺条件下存在DNA损伤与修复的动态变化过程,DNA损伤后可能直接诱导细胞凋亡,DNA损伤程度在早期与细胞凋亡程度相一致.     

DNA pol β,Ku80与鼻咽癌放射敏感性的关系

目的:研究人鼻咽癌细胞系CNE-2Z亚克隆株F1、S1放射后DNA修复相关基因DNA pol β和Ku80的表达,探讨CNE-2Z存在放射敏感性异质性的可能机理。方法:裸鼠体内移植瘤实验观察F1、S1放射后的体内增殖能力,采用Western blot、免疫细胞化学和免疫组织化学方法检测放射后F1和S1 DNA修复相关蛋白(DNA pol β、Ku80)的表达,Feulgen染色法和图像分析方法检测放射后F1、S1裸鼠体内移植瘤的DNA倍体及细胞周期分布情况。结果:未照射前F1细胞DNA pol β和Ku80的表达高于S1;放射后S1细胞DNA pol β及Ku80表达上调的时间较F1早,上调辐度大于F1。鼻咽癌细胞系CNE-2Z确实存在放射敏感性的异质性,放射后S1体内增殖能力大于F1,较多细胞处于有利于DNA修复的G2/M期(P<0.01)。放射后F1、S1裸鼠移植瘤细胞和组织中,DNA pol β和Ku80蛋白表达差异无统计学意义(P>0.05)。结论:本实验进一步证实了鼻咽癌细胞系CNE-2Z确实存在放射敏感性的异质性,F1、S1放射敏感性的差异与两株细胞的DNA修复相关基因(DNA pol β、Ku80)的表达差异所致的DNA SSB、DSB修复的速度和忠实性有关。     

DNA repair alterations in common pediatric malignancies.

DNA repair is an important defense mechanism against DNA damage and includes four distinct pathways: direct, excision, mismatch, and double-strand break repair systems. Recent evidence suggests that alterations in proteins participating in the DNA repair systems may result in cellular senescence, cell death, and neoplastic transformation. Malignancies in adulthood exhibit genomic instability and an increased mutation rate due to underlying defects in DNA repair. However, our knowledge on DNA repair defects, both in germline and somatic mutations, and their relationship with childhood malignancies remains incomplete. Mutations, gene deletions, and inversions in various DNA repair genes have been reported and special attention has recently been focused on the interaction between these abnormalities and malignant transformation in childhood. The purpose of this review is to summarize the existing clinical information concerning components of the DNA repair systems and their influence on the development of the most common pediatric malignancies, including leukemia, tumors of the central nervous system, rhabdomyosarcoma, and retinoblastoma. Such information could possibly explain the response or resistance to chemotherapy and the possible risk of relapse in childhood malignancies presenting specific DNA repair defects. Additionally, these data could be beneficial for the development of novel therapeutic strategies.     

老年小鼠脾细胞DNA修复能力的变化及gadd45和gadd153基因的可诱导性改变

目的：研究小鼠脾细胞ＤＮＡ修复能力的增龄变化以及这种变化的发生与损伤可诱导的ｇａｄｄ４５、ｇａｄｄ１５３基因表达的关联。方法：以紫外线损伤脾细胞ＤＮＡ,用非程序ＤＮＡ合成和单细胞凝胶电泳试验测定ＤＮＡ修复能力;用Ｎｏｒｔｈｅｒｎ杂交方法检测紫外线损伤后ｇａｄｄ４５、ｇａｄｄ１５３基因转录水平的变化。结果：老年小鼠脾细胞ＤＮＡ修复能力低于青年鼠,老年鼠ｇａｄｄ４５和ｇａｄｄ１５３基因的紫外线损伤的可诱导性也低于青年鼠。结论：小鼠脾细胞ＤＮＡ修复能力随增龄而下降,这种变化的发生可能与老年小鼠脾细胞在紫外线损伤后ｇａｄｄ４５、ｇａｄｄ１５３ｍＲＮＡ表达的可诱导性下降有关。     

精子DNA损伤与受精后依赖于卵母细胞修复的研究

迄今为止,人们普遍认为成熟精子DNA损伤后不能自行修复。由于DNA损伤精子仍具有受精能力和发育潜力,其修复可能在受精后阶段,但其具体修复机制还不清楚。目前,对于DNA损伤精子受精后依赖于卵母细胞修复机制的研究已成为热点。现对DNA损伤精子受精后的细胞反应、可能的卵母细胞修复路径、修复结果及其对胚胎发育和后代遗传风险的影响进行综述。     

错配修复基因与口腔鳞状细胞癌关系的研究进展

DNA在复制过程中常常自发地出现碱基错配,碱基错配由错配修复基因负责修复,从而使DNA复制错误减少1000倍以上。一旦错配修复基因发生缺陷,就会造成碱基错配的积聚,DNA突变率增加,在不能有效修复的情况下影响到癌基因和抑癌基因、细胞的增殖和凋亡,从而引起肿瘤发生。本文就错配修复基因与口腔鳞状细胞癌的发生、发展的相关性予以综述。     

ERCC1 and ERCC2 polymorphisms and risk of idiopathic azoospermia in a Chinese population

The ERCC1(excision repair cross complementation group 1) and ERCC2(excision repair cross complementation group 2) genes are important in repairing DNA damage and genomic instability in germ cells, and are essential for normal spermatogenesis. It has been verified that polymorphisms of these two genes could alter DNA repair capacity in some phenotypic studies. However, little information is available on these polymorphisms in male infertility. This study was designed to examine whether ERCC1 polymor- phisms ...     

增殖细胞核抗原和脑缺血损伤

增殖细胞核抗原(PCNA)是真核生物复制复合体的核心成分,为DNA合成所必需。此外它与多种蛋白结合,参与了DNA修复、DNA甲基化、染色体重塑、细胞周期调控和凋亡等许多细胞重要事件。脑缺血后出现神经元细胞DNA修复、胶质细胞增生以及细胞凋亡等,PCNA在其中发挥了重要作用,因此受到人们的广泛关注。兹将PCNA的分子生物学特点、功能及其在脑缺血损伤中的作用简要综述。     

癌家族成员DNA修复能力,染色体脆性部位及染色体畸变率的比较

同时对7个癌家族40名成员的DNA修复能力,染色体畸变率及染色体脆性部位进行分析,结果发现癌家族成员中DNA修复能力低于正常者占80％(32/40),畸变率高于3％者占85％(34/40),染色体脆性部位检出率亦明显增高;DNA修复能力和染色体畸变率均异常者占70％(28/40),表明三项指标在癌家族成员中存在一定的重叠。这种重叠是否增加个体的患癌几率,尚有待长期追随确定.     

DNA damage and repair in lymphoblastoid cell lines from normal donors and fragile X syndrome patients

BACKGROUND: Because lymphocytes from fragile X patients have been reported as hypersensitive to bleomycin-induced chromatid breaks and because the number of trinucleotide repeats in families with fragile X syndrome has a propensity to expand, we have investigated the possibility that fragile X cells may be hypersensitive to DNA damage and have a lower capacity for DNA repair. METHODS: Lymphocytes from normal and fragile X syndrome donors were immortalized by Epstein-Barr virus transformation. Characteristics of fragile X syndrome including the folate-sensitive fragile site on chromosome Xq27.3, length of CGG repeat expansion, and FMRP expression in Epstein-Barr virus-transformed lymphoblastoid cell lines were analyzed by standard cytogenetic methods, Southern blot, and Western blot, respectively. Analysis of DNA damage and repair induced by hydrogen peroxide, bleomycin, ethyl methanesulfonate, 4-nitroquinoline-N-oxide, etoposide, and mitomycin C was carried out by single-cell gel electrophoresis assay (known as comet assay). RESULTS: Lymphoblastoid cell lines from fragile X donors had a folate-sensitive fragile site on chromosome Xq27.3, no or low FMRP expression, and expansion of the CGG repeat. Results of comet assay showed that fragile X cells were not more sensitive to mutagen-induced DNA strand breaks and did not have lower DNA repair capacity in comparison with normal cells. Furthermore, one fragile X cell line showed hyposensitivity to DNA strand breaks induced by hydrogen peroxide, bleomycin, and ethyl methansulfonate. CONCLUSIONS: The results of this study do not support the notion that CGG trinucleotide expansion in fragile X syndrome is caused by permanent deficiency in DNA repair.     

Association between polymorphisms of DNA repair gene XRCC1 and DNA damage in asbestos-exposed workers

INTRODUCTION Asbestos is an important environmental carcinogen and remains the primary occupational concern in many countries. The most important pulmonary disease associated with asbestos fiber exposure is asbestosis (diffuse interstitial pulmonary fibro…     

再生障碍性贫血患者DNA损伤修复活性检测

用盐酸氮芥和紫外线作为ＤＮＡ损伤修复诱导剂，对２４例再生障碍性贫血（再障）骨髓单个核细胞及３３例再障外周血单个核细胞的ＤＮＡ损伤修复活性进行了检测。发现再障患者的脱氧核糖核酸损伤修复活性明显低于正常（Ｐ＜０．０５），其低下与患者贫血程度、骨髓增生状况无关，临床治疗也不易纠正。提示患者ＤＮＡ修复活性低下可能在再障的发生中起重要作用。     

Assessment of Human DNA Repair （NER） Capacity With DNA Repair Rate （DRR） by Comet Assay

INTRODUCTION DNA repair is a defense system to protect the integrity of genome.Deficiencies in this system can result in the development of cancer.Inter-individual variability in human response to carcinogens have been studied repeatedly.More attention ha…     

XRCC3多态性与肺癌易感性关系的研究进展

X线损伤修复的交叉互补基因3(XRCC3)是一种DNA损伤修复基因,其多态性能够改变DNA修复功能和效率、影响肿瘤易感性。许多研究报道XRCC3多态性可能与肺癌易感性有关,但也有二者无相关性的报道,结论不一致可能与种族、地域等多种因素有关。在此就二者的关系的研究进展予以综述。     

放射线对帕金森病淋巴细胞损伤及修复的影响

目的 :探讨帕金森病患者基因损伤和基因修复的关系。方法 :采用淋巴细胞分层液快速提取 30例帕金森病患者和 30例正常对照的外周血淋巴细胞 ,用X线照射的方法造成淋巴细胞的DNA损伤 ,然后进行细胞培养 ,计算照射后平均存活率来检测细胞对X线型基因损伤的基因修复能力。结果 :帕金森病患者外周血淋巴细胞对X线型基因损伤的修复能力下降 (P <0 .0 0 1)。结论 :帕金森病患者的培养淋巴细胞对X线型基因损伤敏感。即基因修复缺陷可能是帕金森病发病机制的重要环节。     

TK6和WTK1细胞对H2O2诱导的DNA损伤和修复能力的比较

目的探讨人的近二倍体类淋巴母细胞TK6和WTK1细胞的DNA损伤和修复能力的差异和机制。方法采用25μmol／L、50μmol／L、100μmol／L的H2O2分别处理TK6和WTK1细胞,对两种细胞进行单细胞凝胶电泳,检测TK6和WTK1细胞的彗星细胞率和彗星细胞尾长以及p53基因的蛋白表达。结果TK6细胞对H2O2诱导的DNA损伤具有较高的敏感性,具有更为快速有效的损伤后修复能力。在孵育0．5h至1h内两种细胞达最大有效修复。TK6细胞P53蛋白本底水平明显低于WTK1细胞,在H2O2处理后,其表达水平明显增强。结论TK6细胞对H2O2诱导的DNA损伤更为敏感,损伤后的修复更为快速、有效。p53基因的表达水平的差异是两种细胞DNA损伤和修复能力差异的重要机制。     

人类hR24L基因参与DNA切除修复和重组修复的研究

目的 研究酵母ＲＡＤ２４基因区域温度敏感突变株校正表型,克隆野生型人类同源基因。方法 用互补试验观察０突变株ｒａｄ２４ＬＲ表型,以人的ｃＤＮＡ表达文库转化突变株,筛选回复表型。结果 ＲＡＤ２４Ｌ能校正突变株辐射敏感表型。以人ｃＤＮＡ表达文库转化ｒａｄ２４ＬＲ,从转化文库后的回复表型中克隆出人类同源基因ｃＤＮＡ,克隆的人类ＲＡＤ２４Ｌ同源基因ｃＤＮＡ蛋白质为６７０个氨基酸,含有一般认定的解螺旋结构或