Drug resistance and membrane alteration in mutants of mammalian cells.
Drug resistance and membrane alteration in mutants of mammalian cells.
复制标题
哺乳动物细胞突变体的耐药性和膜改变。
DOI：
10.1139/g75-064
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发表时间：
1975
期刊：
影响因子：
--
通讯作者：
V. Ling
中科院分区：
文献类型：
--
作者：
V. Ling
中国仓鼠卵巢细胞对秋水仙碱的渗透性降低，已分离出独立的秋水仙碱抗性突变体。这些膜改变突变体的一个显著特征是它们对各种不相关化合物的多效性交叉抗性。体细胞杂种的遗传特性表明，秋水仙素抗性和对其他药物的交叉抗性在体细胞杂种中占主导地位。已分离出对秋水仙碱的抗性降低和对其他药物的抗性相应降低的回复突变体。这些结果有力地表明，秋水仙素抗性和多效性交叉抗性是同一突变的结果。生化研究表明，虽然秋水仙素被运送到我们的细胞通过被动扩散，没有重大的改变，在突变体细胞中可以检测到的膜脂。然而，在这些细胞中似乎存在能量依赖性过程，其积极地维持对秋水仙碱和其他药物的渗透性屏障。在这个过程中，细胞可能会发生变化。在突变细胞膜中发现了一种新的糖蛋白，它在亲本细胞中不存在，在回复突变细胞中大大减少。秋水仙素抗性的模型提出，这表明，某些膜蛋白，如新的糖蛋白的细胞膜流动性（mmf蛋白）的调节剂，其分子构象调节膜渗透性的各种化合物，并在其mmf蛋白的突变体被改变。的可能的重要性，研究化疗相关的耐药性方面的模型的p53细胞进行了讨论。
Independent colchicine-resistant (CHR) mutants of Chinese hamster ovary cells displaying reduced permeability to colchicine have been isolated. A distinguishing feature of these membrane-altered mutants is their pleiotropic cross-resistance to a variety of unrelated compounds. Genetic characterization of the CHR lines indicate that colchicine resistance and cross-resistance to other drugs are of a dominant nature in somatic cell hybrids. Revertants of CHR have been isolated which display decreased resistance to colchicine and a corresponding decrease in resistance to other drugs. These results strongly suggest that colchicine resistance and the pleiotropic cross-resistance are the result of the same mutation(s). Biochemical studies indicate that although colchicine is transported into our cells by passive diffusion, no major alterations in the membrane lipids could be detected in mutant cells. However, there appears to be an energy-dependent process in these cells which actively maintains a permeability barrier against colchicine and other drugs. The CHR cells might be altered in this process. A new glycoprotein has been identified in mutant cell membranes which is not present in parental cells, and is greatly reduced in revertant cells. A model for colchicine-resistance is proposed which suggests that certain membrane proteins such as the new glycoprotein of CHR cells, are modulators of membrane fluidity (mmf proteins) whose molecular conformation regulates membrane permeability to a variety of compounds and that the CHR mutants are altered in their mmf proteins. The possible importance of the CHR cells as models for investigating aspects of chemotherapy related to drug resistance is discussed.