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在对秋水仙碱和其他一些药物的质膜通透性降低的黑线仓鼠细胞系中的基因扩增。

Gene amplification in Djungarian hamster cell lines possessing decreased plasma membrane permeability for colchicine and some other drugs.

作者信息

Gudkov A V, Massino J S, Chernova O B, Kopnin B P

出版信息

Chromosoma. 1985;92(1):16-24. doi: 10.1007/BF00327241.

DOI:10.1007/BF00327241
PMID:2988876
Abstract

By multistep selection a set of clones and sublines possessing different levels of resistance to colchicine or adriablastin was obtained from the SV40-transformed Djungarian hamster cell lines, DM-15 and DMcap. Resistance to both colchicine and adriablastin is associated with an alteration of plasma membrane permeability leading to a decreased uptake of various drugs (3H-colchicine, 3H-cytochalasin B, 3H-actinomycin D, 3H-puromycin, 3H-vinblastine, 14C-chloramphenicol). The DNA of cells highly resistant to cholchicine can transmit resistance only to low dosages of the drug. Comparison of DNAs from wild-type and resistant cells digested by restriction endonucleases revealed new classes of repeated DNA sequences in resistant cell lines. The degree of DNA repetition was correlated with the level of drug resistance. The repeated DNA sequences evidently represent parts of the genome that are amplified in resistant cells. The size of the amplified sequences is 200-250 kilobase pairs (kb). Cell lines highly resistant to colchicine contain amplified DNA, which like mitochondrial DNA replicate asynchronously with the main portion of the cellular DNA and related but not identical DNA sequences are amplified in independent cell lines selected for resistance to colchicine, adriablastin, and actinomycin D. These cell lines display similar patterns of alterations of plasma membrane permeability. The amplified DNA sequences may contain a gene or genes the overexpression of which leads to change in plasma membrane permeability and a development of resistance to various drugs.

摘要

通过多步选择，从经SV40转化的黑线仓鼠细胞系DM - 15和DMcap中获得了一组对秋水仙碱或阿霉素具有不同抗性水平的克隆和亚系。对秋水仙碱和阿霉素的抗性都与质膜通透性的改变有关，这导致各种药物（3H - 秋水仙碱、3H - 细胞松弛素B、3H - 放线菌素D、3H - 嘌呤霉素、3H - 长春碱、14C - 氯霉素）的摄取减少。对秋水仙碱高度抗性的细胞DNA只能将抗性传递给低剂量的该药物。用限制性内切酶消化野生型和抗性细胞的DNA进行比较，发现在抗性细胞系中有新的重复DNA序列类别。DNA重复程度与耐药水平相关。重复的DNA序列显然代表了在抗性细胞中扩增的基因组部分。扩增序列的大小为200 - 250千碱基对（kb）。对秋水仙碱高度抗性的细胞系含有扩增的DNA，其像线粒体DNA一样与细胞DNA的主要部分异步复制，并且在为抗秋水仙碱、阿霉素和放线菌素D而选择的独立细胞系中扩增出相关但不相同的DNA序列。这些细胞系表现出相似的质膜通透性改变模式。扩增的DNA序列可能包含一个或多个基因，其过表达导致质膜通透性改变以及对各种药物产生抗性。

相似文献

1
Gene amplification in Djungarian hamster cell lines possessing decreased plasma membrane permeability for colchicine and some other drugs.在对秋水仙碱和其他一些药物的质膜通透性降低的黑线仓鼠细胞系中的基因扩增。
Chromosoma. 1985;92(1):16-24. doi: 10.1007/BF00327241.
2
[Changes in the genotype and phenotype determining the resistance of Djungarian hamster somatic cells to adriablastin].[决定黑线毛足鼠体细胞对阿霉素抗性的基因型和表型变化]
Biull Eksp Biol Med. 1983 Sep;96(9):92-4.
3
[Isolation of DNA probes for the detection of sequences amplified in colchicine-resistant cells].[用于检测秋水仙碱抗性细胞中扩增序列的DNA探针的分离]
Mol Biol (Mosk). 1986 Jan-Feb;20(1):146-53.
4
Regular pattern of karyotypic alterations accompanying gene amplification in Djungarian hamster cells: study of colchicine, adriablastin, and methotrexate resistance.伴随黑线仓鼠细胞基因扩增的核型改变规律：秋水仙碱、阿霉素和甲氨蝶呤抗性研究
Chromosoma. 1985;92(1):25-36. doi: 10.1007/BF00327242.
5
Cloning and characterization of DNA sequences amplified in multidrug-resistant Djungarian hamster and mouse cells.多药耐药的黑线毛足鼠和小鼠细胞中扩增的DNA序列的克隆与特性分析
Somat Cell Mol Genet. 1987 Nov;13(6):609-19. doi: 10.1007/BF01534481.
6
[Hyperproduction of a specific protein in cells resistant to colchicine and adriablastin].[在对秋水仙碱和阿霉素耐药的细胞中一种特定蛋白质的过度产生]
Biull Eksp Biol Med. 1983 Sep;96(9):95-6.
7
[Cloning and characteristics of DNA sequences amplified in Djungarian hamster cells with multidrug resistance].[在多药耐药的黑线仓鼠细胞中扩增的DNA序列的克隆与特性分析]
Mol Gen Mikrobiol Virusol. 1987 Apr(4):14-9.
8
[Amplification of portions of the genome in mammalian somatic cells resistant to colchicine. VI. Restriction analysis of the amplified DNA sequences].[对秋水仙碱抗性哺乳动物体细胞中基因组部分片段的扩增。VI. 扩增DNA序列的限制性分析]
Genetika. 1983 Jul;19(7):1045-53.
9
[Amplification of portions of the genome in mammalian somatic cells resistant to colchicine. II. Marker chromosomes with long homogeneously staining regions in colchicine-resistant cells of the Djungarian hamster].[秋水仙素抗性哺乳动物体细胞中基因组部分区域的扩增。II. 黑线仓鼠秋水仙素抗性细胞中带有长的均匀染色区的标记染色体]
Genetika. 1982 Sep;18(9):1513-23.
10
[Amplification of portions of the genome in the somatic cells of mammals resistant to colchicine. IV. Genetic transformation using amplified genes from Djungarian hamster cells highly resistant to colchicine].[对秋水仙碱有抗性的哺乳动物体细胞中基因组部分片段的扩增。IV. 使用来自对秋水仙碱高度抗性的黑线仓鼠细胞的扩增基因进行遗传转化]
Genetika. 1983 Jun;19(6):864-71.

引用本文的文献

1
Regular pattern of karyotypic alterations accompanying gene amplification in Djungarian hamster cells: study of colchicine, adriablastin, and methotrexate resistance.伴随黑线仓鼠细胞基因扩增的核型改变规律：秋水仙碱、阿霉素和甲氨蝶呤抗性研究
Chromosoma. 1985;92(1):25-36. doi: 10.1007/BF00327242.
2
Multidrug resistance of DNA-mediated transformants is linked to transfer of the human mdr1 gene.DNA介导的转化体的多药耐药性与人类mdr1基因的转移有关。
Mol Cell Biol. 1986 Nov;6(11):4039-45. doi: 10.1128/mcb.6.11.4039-4045.1986.
3
A 22-kd protein (sorcin/V19) encoded by an amplified gene in multidrug-resistant cells, is homologous to the calcium-binding light chain of calpain.

本文引用的文献

1
Satellite DNA in large marker chromosomes of methotrexate-resistant mouse cells.甲氨蝶呤抗性小鼠细胞大标记染色体中的卫星DNA
Cell. 1980 Mar;19(3):709-15. doi: 10.1016/s0092-8674(80)80047-x.
2
Specific karyotypic alterations in colchicine-resistant cells.秋水仙碱抗性细胞中的特定核型改变。
Cytogenet Cell Genet. 1981;30(1):11-4. doi: 10.1159/000131582.
3
Increased synthesis of a low molecular weight protein in vincristine-resistant cells.长春新碱耐药细胞中一种低分子量蛋白质的合成增加。
一种由多药耐药细胞中扩增基因编码的22-kd蛋白（索辛/V19），与钙蛋白酶的钙结合轻链同源。
EMBO J. 1986 Dec 1;5(12):3201-8. doi: 10.1002/j.1460-2075.1986.tb04630.x.
Biochem Biophys Res Commun. 1981 Mar 16;99(1):228-35. doi: 10.1016/0006-291x(81)91736-8.
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Gene amplification and gene correction in somatic cells.体细胞中的基因扩增与基因校正。
Cell. 1982 May;29(1):109-19. doi: 10.1016/0092-8674(82)90095-2.
5
Onc gene amplification in promyelocytic leukaemia cell line HL-60 and primary leukaemic cells of the same patient.早幼粒细胞白血病细胞系HL-60及同一患者原代白血病细胞中的癌基因扩增。
Nature. 1982 Sep 2;299(5878):61-3. doi: 10.1038/299061a0.
6
Cloned cDNA sequences of the hypoxanthine/guanine phosphoribosyltransferase gene from a mouse neuroblastoma cell line found to have amplified genomic sequences.从小鼠神经母细胞瘤细胞系中克隆出次黄嘌呤/鸟嘌呤磷酸核糖转移酶基因的cDNA序列，该细胞系被发现具有扩增的基因组序列。
Proc Natl Acad Sci U S A. 1982 Mar;79(6):1950-4. doi: 10.1073/pnas.79.6.1950.
7
Correlation of double-minute chromosomes with unstable multidrug cross-resistance in uptake mutants of neuroblastoma cells.神经母细胞瘤细胞摄取突变体中双微体染色体与不稳定多药交叉耐药性的相关性
Proc Natl Acad Sci U S A. 1981 Jun;78(6):3654-8. doi: 10.1073/pnas.78.6.3654.
8
Chromosomal and extrachromosomal localization of amplified dihydrofolate reductase genes in cultured mammalian cells.培养的哺乳动物细胞中扩增的二氢叶酸还原酶基因的染色体和染色体外定位。
Cold Spring Harb Symp Quant Biol. 1981;45 Pt 2:785-97. doi: 10.1101/sqb.1981.045.01.097.
9
[Actinomycin D and 6-mercaptopurine-resistant Djungarian hamster cell line: karyotype, morphology, malignancy].[放线菌素D和6-巯基嘌呤抗性的黑线仓鼠细胞系：核型、形态学、恶性程度]
Genetika. 1981;17(3):460-8.
10
Amplification of the metallothionein-I gene in cadmium-resistant mouse cells.金属硫蛋白-I基因在耐镉小鼠细胞中的扩增。
Proc Natl Acad Sci U S A. 1981 Apr;78(4):2110-4. doi: 10.1073/pnas.78.4.2110.