Efficient nucleotide excision repair of cisplatin, oxaliplatin, and bis-aceto-ammine-dichloro-cyclohexylamine-platinum(IV) (JM216) platinum intrastrand DNA diadducts

Tumors exhibit a spectrum of cellular responses to chemotherapy ranging fro m extreme sensitivity to resistance, either intrinsic or acquired. These va riable responses are both patient and tumor specific. For platinum DNA-dama ging agents,drug resistance depends on the carrier ligand of the platinum c omplex and is due to a combination of mechanisms including DNA repair. Nucl eotide excision repair is the only known mechanism by which bulky adducts, including those generated by platinum chemotherapeutic agents, are removed from DNA in human cells. In this report, we show that the types of DNA lesi ons generated by three platinum drugs, cisplatin, oxaliplatin, and (Bis-ace to-ammine-dichloro-cyclohexylamine-platinum(IV) (JM216), are repaired is vi tro with similar kinetics by the mammalian nucleotide excision repair pathw ay.