TRANSFORMATION OF RAT OVARIAN EPITHELIAL AND RAT-1 FIBROBLAST CELL-LINES BY RAST24 DOES NOT INFLUENCE CISPLATIN SENSITIVITY

Recent reports suggest that expression of an activated c-Ha-ras oncoge ne is associated with cisplatin resistance in NIH-3T3 fibroblasts. To investigate the generality of these observations, cisplatin cytotoxici ty was determined in a series of clonal Rat-1 fibroblast and rat ovari an surface epithelial (ROSE) cell lines carrying a zinc-inducible meta llothionein-RAST24 fusion gene, MTRAST24. Cisplatin sensitivity in RAS -transformed 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 mut ant p21Ha-RAS varied more than 40-fold in these fibroblast sublines. S imilarly, there was no difference in cisplatin sensitivity between par ental ROSE controls, neomycin phosphotransferase transfected controls, or MTRAST24 transfectants. Finally, the cisplatin sensitivity of RAS- transformed ROSE cells was similar to that of spontaneously transforme d 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.