DNA adduct (particularly platinum-DNA adduct) (Pt-DNA adduct)

Platinum-DNA adducts are covalent complexes formed when platinum-based chemotherapeutics react with purine bases in DNA, especially the N7 position of guanine, resulting in intra-strand and inter-strand crosslinks. These adducts block DNA replication and transcription, trigger cell cycle arrest, and activate programmed cell death (apoptosis) when DNA repair is overwhelmed. The efficacy and toxicity of platinum anti-cancer agents largely depend on the formation, persistence, and repair of these adducts. Bifunctional adducts (such as Pt-d(GpG)) are most common and most cytotoxic[2][9]. Resistance to therapy often arises from increased DNA repair, particularly via the nucleotide excision repair pathway (NER) and its central protein ERCC1[3][9]. Platinum-DNA adducts can also serve as pharmacodynamic biomarkers, and their formation underpins most acute and chronic toxicities of platinum drugs, especially in the kidney and nervous system[9].

Other names

Platinum-DNA adductCisplatin-DNA adductCarboplatin-DNA adductOxaliplatin-DNA adductPt-DNA crosslink

Formation of intra- and inter-strand DNA crosslinks by platinum binding to guanine N7, especially as bifunctional adducts (e.g., Pt-d(GpG), Pt-d(ApG)) Structural distortion of DNA, stalling replication and transcription machinery Activation of DNA damage response pathways, including nucleotide excision repair (NER) Induction of apoptosis when repair is insufficient