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 adduct s, causing G2 arrest in the cell cycle, and then triggering apoptosis. A sublethal dose induces drug resistance by several mechanisms, inclu ding changes in drug uptake and efflux, glutathione and metallothionei n levels, and DNA repair. Cisplatin-DNA adducts bind several cellular proteins, including some that enhance survival of the cell by mediatin g DNA repair and others that hasten its death by conferring sensitivit y to the drug.