DECREASE OF PLATINUM ACCUMULATION IN A CISPLATIN-RESISTANT CHINESE-HAMSTER OVARY CELL-LINE

Cisplatin-resistant cells, Pt-r6, were developed through the chronic exposure of Chinese hamster ovary (CHO-K1) cells to increasing concentrations of cisplatin. The LD50 of clonogenic survival after a 2-h cisplatin treatment was 16.3 and 7-mu-M for resistant Pt-r6 and parental CHO-K1 cells, respectively. An analysis of cellular DNA adducts by cisplatin-DNA monoclonal antibodies using the ELISA or flow cytometric methods of adduct-antibody conjugation with fluorescent dye revealed that more adducts were induced in CHO-K1 cells than in Pt-r6 cells. Moreover, CHO-K1 cells also accumulated more cisplatin than Pt-r6 cells, as determined by inductively coupled plasma-atomic emission spectrometry. Thus, resistance to cisplatin was clearly correlated with decreased amounts of platinum and cisplatin-DNA adducts in the resistant cells as compared to the sensitive cells. These results suggest that the reduced accumulation of cisplatin may be involved in the cisplatin resistance of Pt-r6 cells.