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.