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 cells from which they were derived. Cisplatin cytotoxicity was determined in three nontransformed (early passage) and three transformed (late passage) ROSE cell lines. Transformed cells were uniformly more sensitive to cisplatin than parental cells (1.5- to 2.6-fold) and grew more rapidly (doubling time range 15-22 hr) than parental cells (28-37 hr). Increased 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 early passage cell lines, but the correlation between GSH and decreased cisplatin sensitivity in the overall panel of cell lines was modest (rho = 0.549). No statistically significant differences in DNA-platinum binding were observed between early and late passage cell lines. However, initial levels of DNA-bound platinum correlated with cisplatin sensitivity (rho = 0.812) in the six-cell-line panel. GSH levels were inversely correlated with cisplatin accumulation (rho = -0.829) and DNA platination (rho = -0.786). Increased cisplatin sensitivity in spontaneously transformed ROSE cell lines showed a weak, inverse relationship with GSH levels, but more strongly correlated with their increased growth kinetics and to DNA platination.
Perez
R P
RP
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Johnson
S W
SW
Handel
L M
LM
O'Dwyer
P J
PJ
Hamilton
T C
TC
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002945:Cisplatin / Q000494:pharmacology*; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D010053:Ovary / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D012016:Reference Values; D013997:Time Factors
D005978:Glutathione; D002945:Cisplatin