Transformation of Rat Ovarian Epithelial and Rat-1 Fibroblast Cell Lines by RAST24 Does Not Influence Cisplatin Sensitivity1

Recent reports suggest that expression of an activated c-Ha-ros onco gene is associated with cisplatin resistance in NIH-3T3 fibroblasts. To investigate the generality of these observations, cisplatin cytotoxicity was determined in a series of clonal Rat-1 fibroblast and rat ovarian surface epithelial (ROSE) cell lines carrying a zinc-inducible metallothioneinRAST24 fusion gene, MTR4ST24. Cisplatin sensitivity in RAS-trsmsformed fibroblast sublines did not differ from parental controls. Induction of mutant RAST24 expression by zinc sulfate did not affect the cisplatin sensitivity of individual cell lines. Expression of mutant p2lH"~KASvaried more than 40-fold in these fibroblast sublines. Similarly, there was no difference in cisplatin sensitivity between parental ROSE controls, neomycin phosphotransferase transfected controls, or MTA' VM 24 transfectants. Finally, the cisplatin sensitivity of IMS-transformed ROSE cells was similar to that of spontaneously transformed ROSE cells. Overall, these observations suggest that there is little relationship between mutant ras expression and cisplatin sensitivity in rat epithelial and fibroblast cell lines.