DETERMINANTS OF CISPLATIN SENSITIVITY IN NORMAL VERSUS SPONTANEOUSLY TRANSFORMED RAT OVARIAN SURFACE EPITHELIAL-CELLS

The chemosensitivity of spontaneously transformed rat ovarian surface epithelial (ROSE) cell lines was compared to that of the parental cell s from which they were derived, Cisplatin cytotoxicity was determined in three nontransformed (early passage) and three transformed (late pa ssage) ROSE cell lines, Transformed cells were uniformly more sensitiv e to cisplatin than parental cells (1.5-to 2.6-fold) and grew more rap idly (doubling time range 15-22 hr) than parental cells (28-37 hr). In creased doubling time correlated with decreased cisplatin sensitivity (rho = 0.771). Cisplatin accumulation did not correlate with cisplatin sensitivity. Glutathione (GSH) levels were higher in two of three ear ly passage cell lines, but the correlation between GSH and decreased c isplatin sensitivity in the overall panel of cell lines was modest (rh o = 0.549). No statistically significant differences in DNA-platinum b inding were observed between early and late passage cell lines, Howeve r, initial levels of DNA-bound platinum correlated with cisplatin sens itivity (rho = 0.812) in the six-cell-line panel, GSH levels were inve rsely correlated with cisplatin accumulation (rho = -0.829) and DNA pl atination (rho = -0.786). Increased cisplatin sensitivity in spontaneo usly transformed ROSE cell lines showed a weak, inverse relationship w ith GSH levels, but more strongly correlated with their increased grow th kinetics and to DNA platination. (C) 1995 Academic Press Inc.