REDUCED PERMEABILITY IN CHO-CELLS AS A MECHANISM OF RESISTANCE TO COLCHICINE
REDUCED PERMEABILITY IN CHO-CELLS AS A MECHANISM OF RESISTANCE TO COLCHICINE
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DOI：
10.1002/jcp.1040830114
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发表时间：
1974-01-01
影响因子：
5.6
通讯作者：
THOMPSON, LH
中科院分区：
文献类型：
--
作者：
LING, V;THOMPSON, LH
从培养的中国仓鼠(CHO)细胞中分离到表型稳定的秋水仙碱抗性(CHR)株。通过在每一步分离抗性菌落，进行连续的单步抗性选择。建立了两种互补的方法，包括全细胞摄取[~3H]秋水仙碱和胞浆提取物结合[~3H]秋水仙碱，分别检测通透性改变和细胞内靶蛋白改变。所有分离的克隆似乎都降低了对药物的通透性，而它们与秋水仙碱的结合能力并没有降低。秋水仙碱摄取量的减少与细胞耐药性密切相关。CHR对其他药物如放线菌素D、长春花碱和秋水仙胺也有交叉耐药，且交叉耐药程度与秋水仙碱耐药程度呈正相关。非离子洗涤剂吐温80增强了秋水仙碱对突变细胞的细胞毒性作用，并提高了秋水仙碱对整个细胞的摄取速率。
Colchicine resistant (CHR) lines of stable phenotype have been isolated from cultured Chinese hamster (CHO) cells. Successive single‐step selections for increasing resistance were performed by isolating resistant colonies at each step. Two complementary assays involving [3H] colchicine uptake by whole cells and binding of [3H] colchicine by cytoplasmic extracts were developed to test for altered permeability and altered intracellular target protein, respectively. All clones isolated appeared to have decreased permeability to the drug while their colchicine‐binding ability was not reduced. The amount of reduction in colchicine uptake correlated strongly with cellular resistance. The CHRlines were also cross resistant to other drugs such as actinomycin D, vinblastine and Colcemid; furthermore, the degree of cross resistance was positively correlated with the degree of colchicine resistance. The non‐ionic detergent Tween 80 potentiated the cytotoxic action of colchicine on mutant cells as well as its rate of uptake into whole cells.