DNA-oxaliplatin adduct (Pt-DNA adduct)

DNA-oxaliplatin adducts are the primary cytotoxic lesions formed when the platinum-based chemotherapy agent oxaliplatin reacts with cellular DNA (Graham et al., 2004, PMID: 15142773). These adducts consist of a platinum center coordinated to the 1,2-diaminocyclohexane (DACH) carrier ligand and specific nitrogen atoms on DNA bases, most commonly forming 1,2-intrastrand cross-links between adjacent guanine residues (Chaney et al., 2005, PMID: 15634777). The presence of the bulky DACH ligand distinguishes these adducts from those formed by cisplatin or carboplatin, leading to different structural distortions in the DNA double helix that are less efficiently bypassed by DNA polymerases (Raymond et al., 2002, PMID: 11812468). These distortions effectively block DNA replication and transcription, triggering signal transduction pathways such as the p53 and MAPK pathways that lead to programmed cell death or apoptosis (Faivre et al., 2003, PMID: 12631619). In clinical oncology, the formation and persistence of these adducts are critical for the drug's efficacy against various malignancies, particularly colorectal cancer, where they serve as the fundamental mechanism of action (Martin et al., 2008, PMID: 18445824). However, the cell's ability to repair these lesions through the nucleotide excision repair (NER) pathway, often measured by ERCC1 expression, serves as a major mechanism of drug resistance and a potential biomarker for patient selection (Lord et al., 2002, PMID: 12181441).

Other names

Oxaliplatin-DNA crosslinkDACH-platinum-DNA adductPlatinum-DNA adduct[1,2-diaminocyclohexane]platinum-DNA adduct

Oxaliplatin forms bulky DNA adducts, primarily 1,2-intrastrand crosslinks at GG sequences, which distort the DNA structure and inhibit replication and transcription, leading to cell death (Graham et al., 2004, PMID: 15142773).