Chen G, Hutter K J, Bullerdiek J, Zeller W J
Institute of Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg.
J Cancer Res Clin Oncol. 1991;117(6):539-42. doi: 10.1007/BF01613285.
In a rat ovarian tumour cell line a 33-fold resistance to cisplatin (O-342/DDP) was developed in vitro by continuous exposure of the parental cell line (O-342) to stepwise increase cisplatin concentration in the culture medium. Both cell lines had a similar growth rate in vitro. Development of resistance was accompanied by a change of the karyotype from heteroploidy in chemosensitive O-342 cells to near diploidy in resistant O-342/DDP cells as shown by chromosome number distribution. This finding was confirmed by measuring cellular DNA content using flow-cytometry analysis. Flow karyotyping showed significant differences in chromosomal DNA contents between both cell lines. Our results suggest that the parent line O-342 consists of at least two subpopulations, a cisplatin-sensitive and a cisplatin-resistant one, corresponding to hyperploidy and near diploidy, respectively. Continuous cisplatin exposure of O-342 cells selectively killed the sensitive fraction, resulting in the karyotypic change observed.
在一个大鼠卵巢肿瘤细胞系中，通过将亲代细胞系（O-342）持续暴露于培养基中逐步增加的顺铂浓度，在体外诱导出了对顺铂33倍的抗性（O-342/DDP）。两种细胞系在体外具有相似的生长速率。抗性的产生伴随着核型的改变，即从化疗敏感的O-342细胞中的异倍体变为抗性的O-342/DDP细胞中的近二倍体，这通过染色体数目分布得以显示。通过流式细胞术分析测量细胞DNA含量证实了这一发现。流式核型分析显示两种细胞系之间染色体DNA含量存在显著差异。我们的结果表明，亲代细胞系O-342至少由两个亚群组成，一个是顺铂敏感亚群，一个是顺铂抗性亚群，分别对应超倍体和近二倍体。O-342细胞持续暴露于顺铂会选择性地杀死敏感部分，从而导致观察到的核型变化。
