...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Variable content of double minute chromosomes is not correlated with degree of phenotype instability in methotrexate-resistant human cell lines.
【24h】

Variable content of double minute chromosomes is not correlated with degree of phenotype instability in methotrexate-resistant human cell lines.

机译：在耐甲氨蝶呤的人类细胞系中，微小染色体的可变含量与表型不稳定性程度无关。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Several variants resistant to 1.8 x 10(-4) M DL-methotrexate (MTX) have been isolated from the human cell lines HeLa BU25 and VA2-B by exposing them to progressively increasing concentrations of the drug. A striking variability of phenotype and chromosome constitution was observed among the different variants. All resistant cell lines exhibited a greatly increased dihydrofolic acid reductase (DHFR) activity and DHFR content; however, the DHFR activity levels varied considerably among the variants, ranging between about 35 and 275 times the parental level. In the absence of selective pressure, the increased DHFR activity was unstable, and in all cell lines but one was completely lost over a period ranging in different variants between 25 and 200 days. The MTX-resistant cells lines showed anomalies in their chromosome constitution, which involved the occurrence of a duplicated set of chromosomes in most cells of some of the variants and the presence of double minute chromosomes in all cell lines. An analysis of the correlation of loss of double minute chromosomes and loss of DHFR activity in the absence of MTX has given results consistent with the idea that the double-minute chromosomes contain amplified DHFR genes. However, the most significant finding is that, in contrast to what has been reported in the mouse system, the recognizable double-minute chromosomes varied greatly in number in different variants without any relationship to either the level of DHFR activity or the degree of instability of MTX resistance in the absence of selective pressure. These and other observations point to the occurrence in the human MTX-resistant variants of another set of DHFR genes, representing a varied proportion of the total, which is associated with the regular chromosomes, and which may be unstable in the absence of selective pressure.
机译：通过从人类细胞系HeLa BU25和VA2-B暴露于逐渐增加的药物浓度中，已分离出对1.8 x 10（-4）M DL-甲氨蝶呤（MTX）具有抗性的几种变体。在不同的变体之间观察到明显的表型和染色体组成变异。所有抗性细胞系均显示出大大提高的二氢叶酸还原酶（DHFR）活性和DHFR含量。然而，DHFR活性水平在变体之间变化很大，在亲本水平的约35至275倍之间。在没有选择压力的情况下，增加的DHFR活性不稳定，并且在所有细胞系中都消失了，但是在25到200天的不同变体中，其中一个完全丧失了。耐MTX的细胞系的染色体组成出现异常，这涉及某些变体的大多数细胞中出现重复的染色体集，并且所有细胞系中都存在双倍染色体。在没有MTX的情况下，对两分钟染色体丢失与DHFR活性损失之间的相关性进行分析，得出的结果与以下观点一致：两分钟染色体包含扩增的DHFR基因。然而，最重要的发现是，与小鼠系统中报道的相反，可识别的两分钟染色体在不同变体中的数量差异很大，与DHFR活性水平或不稳定性程度无关。在没有选择压力的情况下耐MTX。这些和其他观察结果表明，在人类MTX抗性变异体中出现了另一组DHFR基因，它们代表总数的不同比例，与规则染色体有关，在没有选择压力的情况下可能不稳定。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号