Deoxyribonucleic acid (DNA) platinum adducts (DNA-Pt adducts)

Deoxyribonucleic acid (DNA) platinum adducts are the primary molecular targets for platinum-based chemotherapeutic agents like cisplatin, carboplatin, and oxaliplatin. These adducts form when the platinum complex enters the cell, loses its leaving groups through aquation, and binds covalently to the N7 atoms of purine bases, especially guanine (Kelland, 2007). The resulting chemical lesions, primarily 1,2-intrastrand crosslinks, induce a sharp bend in the DNA double helix, which disrupts the binding of regulatory proteins and the movement of polymerases. This interference with DNA replication and transcription is the fundamental mechanism by which these drugs exert their cytotoxic effects on rapidly dividing cancer cells. The cellular recognition of these adducts by high-mobility group (HMG) proteins and the subsequent failure of repair mechanisms, such as nucleotide excision repair (NER), lead to the induction of apoptosis (Wang & Lippard, 2005). While these adducts are highly effective in treating malignancies like testicular and ovarian cancers, their formation in healthy tissues is associated with dose-limiting toxicities, including nephrotoxicity and neurotoxicity. Furthermore, the ability of cells to repair these adducts or tolerate their presence is a major determinant of clinical drug resistance (Dasari & Tchounwou, 2014). The study of these adducts remains critical for developing next-generation platinum drugs with improved safety profiles and broader efficacy.

Other names

Platinum-DNA adductsPt-DNA lesionsDNA-platinum crosslinksCisplatin-DNA adductsCarboplatin-DNA adductsOxaliplatin-DNA adductsDNA-platinum adduct sites

Platinum-based drugs undergo intracellular activation to form reactive species that covalently bind to the N7 position of purine bases (predominantly guanine) in DNA, creating crosslinks that inhibit replication and transcription and trigger apoptosis (Wang & Lippard, 2005; Dasari & Tchounwou, 2014).