BGC823和A549细胞染色体着丝粒点变异

癌细胞的一个显著细胞遗传学特征是染色体非整倍性畸变,但其畸变的机制至今仍然不清。因此,本文从与染色体分离直接相关的着丝粒点变异的角度,采用Cd-NOR同步银染技术对BGC823细胞和A549细胞染色体Cd变异进行了分析,以探索癌细胞非整倍性畸变的发生机制。结果表明：（1）BGC823细胞染色体Cd缺失率为1.75%、迟滞复制率为0.28%、小Cd率为1.82%、Cd-NOR融合率为0.95%,与正常人胚胎绒毛细胞染色体Cd相比较,BGC823细胞染色体Cd缺失和Cd-NOR融合显著升高（P＜0.0125）,而Cd迟滞复制和小Cd两者没有显著性差异。（2）A549细胞染色体Cd缺失率为2.73%、迟滞复制率为0.94%、小Cd率为1.73%、Cd-NOR融合率为0.71%,与正常人胚胎绒毛细胞染色体Cd相比较,A549细胞染色体Cd缺失和Cd迟滞复制显著升高（P＜0.0125）,而小Cd和Cd-NOR融合两者没有显著性差异。提示BGC823细胞染色体非整倍性畸变可能主要源于Cd缺失和Cd-NOR融合,而A549细胞染色体非整倍性畸变可能主要源于Cd缺失和Cd迟滞复制。     

不良孕产夫妇着丝粒—动粒复合体的细胞遗传学研究

为研究不良孕产夫妇着丝粒－动粒复合体（centromere kinetochore complex,CKC)变异与不良孕产的相关性,探索不良孕产中非整倍体表成的细胞遗传学基础,应用改良的着丝粒点－核仁组织区（Cd-NOR)同步银染技术,分别对53对不明原因的不良孕产夫妇和57对已生育正常儿的正常夫妇外周血淋巴细胞染色体CKC变异类型及频率进行研究和分析。结果发现,不良孕产夫妇其小Cd,Cd消失、Cd迟滞和Cd-NOR融合频率均较正常对照组明显增高,两相比有显性差异（P＜0．05）。CKC变异频率增高可能是导致不良孕产非整倍体形成的主要原因之一。     

染色体倍性的几个重要概念及表示方法

为清楚理解和掌握染色体数目变异的内容,必须弄清有关染色体数目变异的一些重要概念,如染色体组、单倍体与一倍体、Zn、n、x符号的含意等。现将一些概念的确切含意叙述如一F。染色体倍性是指细胞中含的染色体组数,又分整倍性和非整信性,整倍性是指细胞中所含有的染色体组都是完整的染色体组,如单倍体、二倍体、三倍体等。非整倍性是指细胞中所含的染色体组处于不完整状态,一般指二倍体种成对染色体的成员增加了或减少了。在二倍体细胞或个体中,能维持配子正常功能,包括一定数目、形态结构和一定基因组成的一套染色体称为染色体组或…     

人类染色体数目畸变类型和机理

正常人体细胞中有４６条染色体,其中２３条来自父方,另２３条来自母方,即含有两个染色体组,称为二倍体（２ｎ）。每号染色体都是成对存在的,如果某号染色体出现了单条、多条或染色体组成倍地增减,将形成染色体数目畸变。１　畸变类型１．１　整倍性变异　即染色体组成倍地增减,若整个染色体组增加可形成多倍体,整个染色体组减少则形成单倍体。在人类中,单倍体或四倍以上的多倍体尚未见报道,三倍体和四倍体多发现于自然流产的胎儿中。１）三倍体　三倍体细胞中有３个染色体组（３ｎ）,即每一号染色体都有３条（３ｎ＝６９）。人类…     

植物离体培养细胞的类减数分裂

PlantSomaticMeiosis-likeDivisioninvitroChenYihuaChenZhenghua(InstituteofGeneties,TheChineseAcademyofSeienees,Beijing100101)在离休培养条件下,相物细胞染色作容易发生数目和结构变异,这些变计包括染色体信性变异、非整倍体的出现、染色体断裂、易位、缺失、落后染色体及染色体桥等[1,3—5,6—8,13,14,21,22,26,28,30）,这此变异是体细胞无性系变异（somaclonalvariation）的来源之一．在众多的报道中,有一种染色体数目减少的现象被人们所注意。过去减数分裂总是与雌雄配子发生过程相连系的、在离休诱导细胞脱分…     

植物染色体基数的异整倍性变异和进化

植物染色体在二倍体水平上的数目变异,主要表现为基数(x)的非整倍性变异或异整倍性变异,这是物种演化的重要途径之一.本文介绍了有关这类变异的实例和变异的机制.     

减数分裂中染色体不分离与染色体病

人类细胞减数分裂是精卵形成过程中的重要阶段。它包括染色体的一次复制 ,细胞的两次连续的分裂以及同源染色体配对、交换 ,同源染色体分离 ,姐妹染色单体分离等一系列复杂的过程。在细胞分裂进入中、后期时 ,如果其一对同源染色体或两姐妹染色单体未分别向两极移动 ,却同时进入一个子细胞中 ,结果细胞分裂所形成的两个子细胞中 ,一个将因染色体数目增多而形成超二倍体 ,一个则由于染色体数目减少而形成亚二倍体。这一过程称染色体不分离 (ｃｈｒｏｍｏｓｏｍａｌｎｏｎ -ｄｉｓｊｕｎｃｔｉｏｎ) ,从而引起配子中染色体数目异常 ,产生非整…     

中国西南地区鹿药属4种15居群核型研究

对产于中国西南部的鹿药属（Maianthemum）4种植物进行了细胞学研究,包括染色体数目,多倍化,非整倍性和随体染色体,以及核型不对称性和核型进化。结果表明：1）除了在云南丽江采集的Maianthemum tatsienensis染色体数目为2n=72之外,其余的居群全为2n=36;2）核型在居群间存在变异,特别是在具中部染色体和近中部染色体的数目以及随体染色体的数目和位置上。此外,M．nanchuanense和M．szechuanicum的核型是首次报道,B染色体也是首次在该属中发现。我们推测鹿药属的进化方式包括频繁的染色体畸变以及不同水平上的多倍化,而中国西南部是该属的分化中心。     

濒危植物巴东木莲花粉母细胞减数分裂观察

对巴东木莲Manglietia patungensis及其近缘种乳源木莲M. yuyuanensis的花粉母细胞减数分裂过程的基本特征进行了比较研究。乳源木莲与巴东木莲的染色体数目和核型相同,但不经任何人为因素诱导,它们之间在减数分裂过程中的染色体行为上有明显差异。(1)巴东木莲减数分裂中期I构型为0.30IV+18.33II+0.15I,与乳源木莲构型19II不同,巴东木莲可能存在同臂内倒位杂合子,染色体结构存在一定的杂合性。(2)后期I和后期II染色体行为异常现象发生频率明显不同。以后期II为例,乳源木莲减数分裂相中有迟滞染色体的细胞占8.8%,迟滞染色体不超过2个;巴东木莲有迟滞染色体等异常现象的细胞占29.2%,迟滞染色体最高达11个,还出现染色体碎裂成断片现象。巴东木莲减数分裂过程中染色体组表现出染色体结构杂合变异和迟滞染色体与染色体的断裂频率很高的异常现象在一定程度上可能影响了雄配子体的发育。     

两广茶区10个茶树品种染色体数目研究

采用植物染色体去壁、低渗、火焰干燥制片技术,分析了两广茶区１０个茶树品种染色体数目。结果表明,这１０个茶树品种均为二倍体（２ｎ＝２ｘ＝３０）;但在广东平远锅　品种中发现３个三倍体细胞;在广东连南大叶种中发现１个单倍体细胞;在清远笔架茶等６个茶树品种中均发现染色体数少于３０条的细胞。研究结果说明,茶树染色体基数具有高度的稳定性,极端气候条件的变化,很可能是导致染色体出现整倍性或非整倍性变异的原因。     

A common link in the mechanism of the self-maintenance of malignant growth: the syndrome of the nonhealing wound

A general principle of the maintenance of malignant growth in all types of tumors has been formulated. According to this principle, stochastic but continuous death of some tumor cells due to the inherent genetic instability of their genome (fragility of chromosomes) is the main event stimulating tumor growth. The dead cells trigger a complex multicomponent process of wound healing expressed as further proliferation of living tumor cells, angiogenesis, stimulation of cell migration, and other events. Stimulation of the proliferation of living cells leads to further death of cells and, as a result, to further stimulation of the system of wound healing, etc. Thus, the tumor sacrifices a small amount of dying cells to stimulate proliferation of all its other cells. It is proposed that the nature of the genetic instability of malignant cells is related to the appearance of an uninemic structure in some regions of chromosomes, in whole chromosomes, or in whole genomes. The author bases his statements on the binemic structure of chromosomes, which has already been experimentally and theoretically substantiated. Uninemic regions have an exceedingly high frequency of spontaneous chromosome aberrations due to blockage of the mechanism of underlying repair of the DNA double break in the absence of a second DNA copy. Possible approaches to a search for more efficient methods of therapy are discussed.     

A common link in the mechanism of the self-maintenance of malignant growth: The syndrome of the nonhealing wound

A general principle of the maintenance of malignant growth in all types of tumors has been formulated. According to this principle, stochastic but continuous death of some tumor cells due to the inherent genetic instability of their genome (fragility of chromosomes) is the main event stimulating tumor growth. The dead cells trigger a complex multicomponent process of wound healing expressed as further proliferation of living tumor cells, angiogenesis, stimulation of cell migration, and other events. Stimulation of the proliferation of living cells leads to further death of cells and, as a result, to further stimulation of the system of wound healing, etc. Thus, the tumor sacrifices a small amount of the dying cells to stimulate the proliferation of all of its other cells. It is proposed that the nature of the genetic instability of malignant cells is related to the appearance of an uninemic structure in some regions of chromosomes, in whole chromosomes, or in whole genomes. The author bases his statements on the binemic structure of chromosomes, which has already been experimentally and theoretically substantiated. Uninemic regions have an exceedingly high frequency of spontaneous chromosome aberrations, due to blockage of the mechanism of underlying repair of the DNA double break in the absence of a second DNA copy. Possible approaches to a search for more efficient methods of therapy are discussed.     

Antitumor activity of cell suspension culture of green tea seed (Camellia sinensis L.)

The objective of this study was to investigate the antitumor activity of suspension cultures of tea callus cells grown in the presence of different concentrations of the growth regulator 2,4-dichlorophenoxy acetic acid (2,4-D) with or without light irradiation. The methanol and ethanol extracts of precipitated cells (MEP, EEP) exhibited stronger inhibitory effects on the growth of tumor cell lines than the water extract of precipitated cells (WEP) or the supernatant. Compared to culture under dark conditions, exposure to light irradiation led to significantly higher antitumor activity. The MEP from light irradiated cells at 250 μg/mL with 2.0 mg/L 2,4-D displayed more than 64% growth inhibition of HEP-2 cells, whereas normal cells showed less than 25% growth inhibition. The some fractions of MEP obtained from Diaion HP-20 column chromatography displayed the majority of inhibitory activity against the HEP-2 cell line. These results show that 2,4-D, and light stimulated the synthesis of antitumor compounds.     

Dual roles of telomere dysfunction in initiation and suppression of tumorigenesis

Human carcinomas arise through the acquisition of genetic changes that endow precursor cancer cells with a critical threshold of cancer-relevant genetic lesions. This complex genomic alterations confer upon precursor cancer cells the ability to grow indefinitely and to metastasize to distant sites. One important mechanism underlying a cell's tumorigenic potential is the status of its telomere. Telomeres are G-rich simple repeat sequences that serve to prevent chromosomal ends from being recognized as DNA double-strand breaks (DSBs). Dysfunctional telomeres resemble DSBs, leading to the formation of dicentric chromosomes that fuel high degrees of genomic instability. In the setting of an intact p53 pathway, this instability promotes cellular senescence, a potent tumor suppressor mechanism. However, rare cells that stochastically lose p53 function emerge from this sea of genomic instability and progress towards cancer. In this review, we describe the use of mouse models to probe the impact of dysfunctional telomeres on tumor initiation and suppression.     

芫菁斑蝥素对喉癌细胞和胃癌细胞的抑制作用

【目的】 研究提取自眼斑芫菁Mylabris cichorii (Linnaeus)体内的斑蝥素对人喉癌HEP-2细胞和人胃癌BGC-823细胞的抑制、以及对细胞周期分布的影响。【方法】 将斑蝥素作用于经体外培养的人喉癌HEP-2细胞和人胃癌BGC-823细胞, 采用MTT法进行体外细胞抑制实验, 测定斑蝥素对这2种癌细胞生长的抑制率与剂量效应;采用流式细胞术测定斑蝥素处理的人喉癌HEP-2细胞的细胞周期;并通过光学显微镜观察其细胞形态学改变。【结果】 斑蝥素浓度为1.28 μmol/L时, 对HEP-2细胞有显著抑制作用, 且随药物浓度升高其抑制作用增强, 呈剂量效应关系, 抑制中浓度为2.88 μmol/L;斑蝥素浓度为20.4 μmol/L时, 对BGC-823细胞有显著抑制作用, 且随药物浓度升高其抑制作用增强, 呈剂量效应关系, 抑制中浓度为54.85 μmol/L。用浓度1.44和2.88 μmol/L的斑蝥素处理HEP-2细胞24 h后, G2-M期分布从8.21%增加到22.29%, S期细胞分布从14.33%增加到21.61%, 且随药物浓度升高其阻滞作用增加, 呈剂量效应关系。G0-G1期细胞分布都有所降低, 从77.45%降低到56.10%, G0-G1期峰前无显著的亚二倍体峰出现, 说明斑蝥素未能够诱导HEP-2细胞发生凋亡。光镜检查显示：HEP-2细胞可出现细胞收缩、胞膜突出、核碎裂等现象。【结论】 斑蝥素对治疗喉癌的效果可能较为理想, 而对胃癌的作用则不明显。     

Cell death evaluation in benzo[a]pyrene-transformed human breast epithelial cells after microcell-mediated transfer of chromosomes 11 and 17

The incidence of apoptosis and nuclear instability, including the incidence of catastrophic death, were investigated in benzo[a]pyrene (BP)-transformed human breast epithelial cells (BP1-E cell line) after microcell-mediated transfer of chromosomes 11 and 17. Since the introduction of normal chromosomes 11 and 17 into tumorigenic human breast BP1-E cells reverts some of these cells' characteristics (especially those affected by microsatellite instabilities and loss of heterozygosity) to those of parental non-transformed MCF-10F cells, it was expected that the cell death rates would also be affected by this treatment. The transfer of the mentioned chromosomes, especially chromosome 17, to tumorigenic BP1-E cells increased the apoptotic ratios and decreased the nuclear instability ratios, thus showing that the microsatellite instability and loss of heterozygosity induced by BP in these chromosomes of MCF-10F cells affect the control of cell death mechanisms.     

Chromosome rearrangements resulting from telomere dysfunction and their role in cancer

Telomeres play a vital role in protecting the ends of chromosomes and preventing chromosome fusion. The failure of cancer cells to properly maintain telomeres can be an important source of the chromosome instability involved in cancer cell progression. Telomere loss results in sister chromatid fusion and prolonged breakage/fusion/bridge (B/F/B) cycles, leading to extensive DNA amplification and large deletions. These B/F/B cycles end primarily when the unstable chromosome acquires a new telomere by translocation of the ends of other chromosomes. Many of these translocations are nonreciprocal, resulting in the loss of the telomere from the donor chromosome, providing a mechanism for transfer of instability from one chromosome to another until a chromosome acquires a telomere by a mechanism other than nonreciprocal translocation. B/F/B cycles can also result in other forms of chromosome rearrangements, including double-minute chromosomes and large duplications. Thus, the loss of a single telomere can result in instability in multiple chromosomes, and generate many of the types of rearrangements commonly associated with human cancer.     

Report on the Eleventh International Workshop on the Identification of Transcribed Sequences 2001. November 9-11, 2001. Washington, DC, USA

Glioblastoma multiforme (GBM) is characterized by intratumoral heterogeneity as to both histomorphology and genetic changes, displaying a wide variety of numerical chromosome aberrations the most common of which are monosomy 10 and trisomy 7. Moreover, GBM in vitro are known to have variable karyotypes within a given tumor cell culture leading to rapid karyotype evolution through a high incidence of secondary numerical chromosome aberrations. The aim of our study was to investigate to what extent this mitotic instability of glioblastoma cells is also present in vivo. We assessed the spatial distribution patterns of numerical chromosome aberrations in vivo in a series of 24 GBM using two-color in situ hybridization for chromosomes 7/10, 8/17, and 12/18 on consecutive 6-microm paraffin-embedded tissue slides. The chromosome aberration patterns were compared with the histomorphology of the investigated tumor assessed from a consecutive HE-stained section, and with the in vitro karyotype of cell cultures established from the tumors. All investigated chromosomes showed mitotic instability, i.e., numerical aberrations within significant amounts of tumor cells in a scattered distribution through the tumor tissue. As to chromosomes 10 and 17, only monosomy occurred, as to chromosome 7 only trisomy/polysomy, apparently as a result of selection in favor of the respective aberration. Conversely, chromosomes 8, 12, and 18 displayed scattered patterns of monosomy as well as trisomy within a given tumor reflecting a high mitotic error rate without selective effects. The karyotypes of the tumor cell cultures showed less variability of numerical aberrations apparently due to clonal adaptation to in vitro conditions. We conclude that glioblastoma cells in vivo are characterized by an extensive tendency to mitotic errors. The resulting clonal diversity of chromosomally aberrant cells may be an important biological constituent of the well-known ability of glioblastomas to preserve viable tumor cell clones under adaptive stress in vivo, in clinical terms to rapidly recur after antitumoral therapy including radio- or chemotherapy.     

The spindle assembly checkpoint: perspectives in tumorigenesis and cancer therapy

Loss or gain of chromosomes, a condition known as aneuploidy, is a common feature of tumor cells and has therefore been proposed as the driving force for tumorigenesis. Such chromosomal instability can arise during mitosis as a result of mis-segregation of the duplicated sister chromatids to the two daughter cells. In normal cells, missegregation is usually prevented by the spindle assembly checkpoint (SAC), a sophisticated surveillance mechanism that inhibits mitotic exit until all chromosomes have successfully achieved bipolar attachment to spindle microtubules. Complete abrogation of SAC activity is lethal to normal as well as to tumor cells, as a consequence of massive chromosome mis-segregation. Importantly, many human aneuploid tumor cells exhibit a weakened SAC activity that allows them to tolerate gains or losses of a small number of chromosomes; and interfering with this SAC residual activity may constitute a suitable strategy to kill cancer cells. This review focuses on the potential link between SAC and tumorigenesis, and the therapeutic strategy to target the SAC for cancer treatment.     

猴头多糖HEP-2化学成分研究

猴头菌(Hericium erinaceus (Bull.) Pers．)的菌丝体培养物经水溶、乙醇沉淀、除蛋白等步骤得到猴头多糖(HEP),利用柱层析从HEP中分离得到两个组分HEP-1和HEP-2。用高效液相凝胶法(HPGPC)鉴定了HEP-2的纯度及分子量,通过有机元素分析、IR、ICP等多种分析方法确定HEP-2为一种硫酸化复合多糖,首次确定了猴头多糖的基本化学组成。