Expression of the c-Ha-ras Oncogene in Mouse NIH 3T3 Cells Induces Resistance to Cisplatin

作者: Franz B. Thiebaut , Doreen K. Hom , Paul A. Andrews , Alakananda Basu , Alan Eastman

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摘要: The effect of expression the c-Ha- ras oncogene on cisplatin (DDP) sensitivity was examined in murine NIH 3T3 cells transfected with dexamethasone (DEX)-inducible mouse mammary tumor virus promoter linked to an activated gene [LTR H-ras(A) cells]. Treatment these 5 µm DEX for 24 h induced and produced 8.2 ± 1.3-fold (SD) increase DDP resistance as quantitated by clonogenic assay. Induction reduced accumulation 40% intrastrand adduct formation 17%. In nontransfected wild-type cells, did not induce nor it decrease accumulation. alter cellular glutathione content or activity glutathione- S -transferase LTR cells. increased metallothionein 1.6-fold 3.3-fold We conclude that DEX-induced overexpression a mutant confers this is associated impairment drug content.

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