Recent reports suggest that expression of an activated c-Ha-ras oncogene 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 metallothionein-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 mutant p21Ha-RAS varied 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 MTRAST24 transfectants. Finally, the cisplatin sensitivity of RAS-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.

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Dr. Perez was supported during this project by grants from U.S. Bioscience and the Mary L. Smith Charitable Lead Trust (04269-06-J). Work from our laboratory is supported by institutional Grants NIH CA 00927, NIH RR0895, the Pew Charitable Trusts (88-01522-000), and appropriations from the Commonwealth of Pennsylvania.

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