Kopnin B P, Godkov A V
Genetika. 1982 Sep;18(9):1513-23.
The series of sublines 170-750 times more resistant to colchicine were obtained from 10 independent clones of Djungarian hamster cells possessing 16-22-fold resistance to the drug. From each clone, several sublines with different levels of colchicine-resistance were developed. The drug resistance was unstable. 2,7-4,0% of cells per population doubling lost resistance to selective dosages of colchicine. The loss of resistance was stepwise. The chromosomes stained by trypsin G-banding technique were studied in 17 sublines. 15 sublines derived from 9 independent clones contained chromosomes with long homogeneously staining regions (HSRs). These were, as a rule, primarily localized in the long arm of chromosome 4. During cultivation, HSRs were transferred from chromosome 4 into other chromosomes. Evidently, transposition of HSRs was due to translocations of different chromosomes of HSRs in the chromosome 4 and to subsequent breakages of the resulting dicentrics within HSRs. A great number of different chromosomal rearrangements was also found in the cells containing HSRs. Possibly, formation of HSR leads to destabilization of the karyotype and to the variability of the genome. The length of HSRs varied in different cells of each subline. The levels of colchicine-resistance in different sublines did not correlate with the average length of HSRs in their cells. The lack of connection between the lengths of HSRs and the levels of drug resistance as well as the existence of highly resistant sublines with gene amplification, but without HSRs, suggest that amplified genes are localized in Djungarian hamster colchicine-resistant cells both in chromosomes and extrachromosomally.
从对秋水仙碱具有16 - 22倍抗性的10个独立的黑线仓鼠细胞克隆中获得了对秋水仙碱抗性高170 - 750倍的一系列亚系。从每个克隆中培养出了几个具有不同秋水仙碱抗性水平的亚系。药物抗性不稳定。每代细胞群体中2.7% - 4.0%的细胞丧失了对选择性剂量秋水仙碱的抗性。抗性丧失是逐步的。对17个亚系的细胞进行了胰蛋白酶G显带技术染色的染色体研究。来自9个独立克隆的15个亚系含有具有长的均匀染色区(HSR)的染色体。这些染色体通常主要位于4号染色体的长臂上。在培养过程中,HSR从4号染色体转移到了其他染色体上。显然,HSR的转位是由于HSR在4号染色体与其他不同染色体之间的易位以及随后在HSR内产生的双着丝粒的断裂。在含有HSR的细胞中还发现了大量不同的染色体重排。可能,HSR的形成导致了核型的不稳定和基因组的变异性。每个亚系的不同细胞中HSR的长度各不相同。不同亚系中秋水仙碱抗性水平与细胞中HSR的平均长度无关。HSR长度与药物抗性水平之间缺乏关联,以及存在具有基因扩增但没有HSR的高抗性亚系,这表明扩增基因在黑线仓鼠秋水仙碱抗性细胞中既定位在染色体上,也定位在染色体外。