Karyotypic change from heteroploidy to near diploidy associated with development of cisplatin resistance in a rat ovarian tumour cell line.
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.
Chen
G
G
Institute of Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg.
Hutter
K J
KJ
Bullerdiek
J
J
Zeller
W J
WJ
D000818:Animals; D002460:Cell Line; D002945:Cisplatin / Q000276:immunology*; D004247:DNA / Q000032:analysis; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D007621:Karyotyping; D010051:Ovarian Neoplasms / Q000235:genetics*; D011003:Ploidies; D051381:Rats
D004247:DNA; D002945:Cisplatin