DIFFERENCES IN THE RATES OF GENE AMPLIFICATION IN NONTUMORIGENIC AND TUMORIGENIC CELL-LINES AS MEASURED BY LURIA-DELBRUCK FLUCTUATION ANALYSIS
DIFFERENCES IN THE RATES OF GENE AMPLIFICATION IN NONTUMORIGENIC AND TUMORIGENIC CELL-LINES AS MEASURED BY LURIA-DELBRUCK FLUCTUATION ANALYSIS
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DOI：
10.1073/pnas.86.23.9441
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发表时间：
1989-12-01
影响因子：
11.1
通讯作者：
LUM, K
中科院分区：
文献类型：
--
作者：
TLSTY, TD;MARGOLIN, BH;LUM, K
据推测，基因组流动性是肿瘤发生的重要组成部分。以前的研究描述了致瘤性与基因组流动性的一个标志物基因扩增之间的关系。在这份报告中，这些研究扩展了大鼠肝上皮细胞系，以显示：（i）这些细胞中的扩增在群体中以自发的方式出现（即，检测到的变异体在群体中不是预先存在的），和（ii）如通过Luria-Delbruck波动分析测量的，自发扩增（突变）的速率在非致瘤细胞中显著低于致瘤细胞。采用Po法和平均数法估计发病率。在高度致瘤细胞中，编码多功能蛋白CAD（含有酶活性氨甲酰磷酸合酶、天冬氨酸转氨甲酰酶和二氢乳清酸酶）的基因的自发扩增速率显著大于非致瘤细胞，几乎达到1 × 10 - 6。10-4每代细胞发生的事件。与哺乳动物细胞中通常报告的点突变率相比，这种致突变事件的发生率较高，将讨论其对致瘤过程的潜在贡献。
It has been hypothesized that genomic fluidity is an important component of tumorigenesis. Previous studies described the relationship between tumorigenicity and one marker for genomic fluidity, gene amplification. In this report, these studies are extended with the rat liver epithelial cell lines to show: (i) the amplification in these cells arises in a spontaneous fashion in the population (i.e., the variants detected are not preexisting in the population), and (ii) the rate of spontaneous amplification (mutation), as measured by Luria-Delbruck fluctuation analysis, is significantly lower in the nontumorigenic cells than in the tumorigenic cells. The rate was estimated by using the Po method and the method of means. The rate of spontaneous amplification of the gene encoding the multifunctional protein CAD (containing the enzymatic activities carbamoyl-phosphate synthase, aspartate transcarbamylase, and dihydroorotase) in the highly tumorigenic cells was significantly greater than that for the nontumorigenic cells, reaching almost 1 .times. 10-4 events per cell generation. The rate of this mutagenic event is high compared to the rate of point mutations usually reported in mammalian cells, and its potential contribution to the tumorigenic process will be discussed.