EXPRESSION OF THE CISPLATIN RESISTANCE PHENOTYPE IN A HUMAN OVARIAN-CARCINOMA CELL-LINE SEGREGATES WITH CHROMOSOME-11 AND CHROMOSOME-16

Many mechanisms have been proposed to explain cisplatin resistance, su ggesting that this phenomenon is multifactorial, In an attempt to defi ne the chromosome(s) responsible for cisplatin resistance in the human ovarian carcinoma 2008/C13 cell lines, somatic cell hybrids were obt ained following fusion of the cisplatin-resistant 2008/C13 cells with an A9 rodent fibroblast cell line, The hybrids were then analyzed for segregation of the human chromosomes with the drug-resistant phenotyp e. Chromosomes 11 and 16 were present in all of the resistant somatic cell hybrids, with the highest concordance for chromosome 16. The role of both of these chromosomes was further established with microcell h ybrids. Microcell hybrids of A9 cells with chromosome 16 from the 2008 /C13 cells did not exhibit cisplatin resistance, but the presence of a normal chromosome 11 viith chromosome 16 (derived from cisplatin-res istant 2008/C13 cells and not from the cisplatin-sensitive 2008 cells ) resulted in increased resistance to cisplatin. In addition, loss of chromosome II from a resistant somatic cell hybrid resulted in the hyb rid becoming sensitive to cisplatin, implicating this chromosome in ma intaining the resistant phenotype. The results demonstrate that resist ance to cisplatin is a dominant trait in the 2008/C13 human ovarian c ells, and both chromosomes 11 and 16 are required for its expression.