Cisplatin–DNA adduct

Cisplatin–DNA adducts are covalent complexes formed when the chemotherapeutic drug cisplatin enters the cell, undergoes aquation, and then binds predominantly to the N7 site of purine bases in DNA—mainly guanine, resulting in 1,2-intrastrand crosslinks (especially d(GpG)), less commonly 1,2-intrastrand d(ApG) and 1,3-intrastrand adducts, and occasionally interstrand crosslinks[1][2][3][5][6][7]. These DNA lesions distort the double helix, block DNA and RNA polymerases, inhibit replication and transcription, and activate intrinsic cellular DNA damage responses, including cell cycle arrest and apoptosis[1][2][3][5][6][7]. The inability to repair these adducts leads to tumor cell death, making the DNA adduct the critical pharmacologic lesion responsible for cisplatin’s anti-cancer effects[1][2][5]. However, enhanced DNA repair capacity and other mechanisms in tumor cells contribute to drug resistance, while adduct formation in normal tissue DNA underlies many therapeutic safety concerns[1][6].

Other names

cisplatin–DNA crosslinkcisplatin–DNA adductcisplatin-damaged DNAPt–DNA adduct

Covalent DNA crosslinking and adduct formation (primarily 1,2-intrastrand crosslinks at guanine residues) Blockage of DNA replication and transcription Activation of DNA damage signaling (leading to cell cycle arrest and apoptosis)