Cellular responses to cisplatin. The roles of DNA-binding proteins and DNA repair.
The anticancer drug cisplatin provokes a complex response in the cell. A lethal dose of the drug kills cells primarily by forming DNA adducts, causing G2 arrest in the cell cycle, and then triggering apoptosis. A sublethal dose induces drug resistance by several mechanisms, including changes in drug uptake and efflux, glutathione and metallothionein levels, and DNA repair. Cisplatin-DNA adducts bind several cellular proteins, including some that enhance survival of the cell by mediating DNA repair and others that hasten its death by conferring sensitivity to the drug.
Chu
G
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Department of Medicine, Stanford University School of Medicine, California 94305.
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002945:Cisplatin / Q000378:metabolism / Q000494:pharmacology*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004351:Drug Resistance; D006801:Humans; D013438:Sulfhydryl Compounds / Q000378:metabolism
D004268:DNA-Binding Proteins; D013438:Sulfhydryl Compounds; D002945:Cisplatin