Contribution of Base Damages to the Molecular Radiosensitization Mechanism of Platinum Chemotherapeutic Drugs

摘要

The measurement of clustered damages in Pt-chemotherapeu- tic-drugs-DNA complexes induced by low-energy (0-30 eV) electrons (LEEs) may provide further understanding of the synergy mechanism in cancer treatment with concomitant chemoradiation therapy (CRT). Five-monolayer films of Pt-DNA complexes, containing cisplatin, carboplatin and oxaliplatin with ratio 5:1 were irradiated with mono-energetic electrons of 10 eV, the most prominent energy for bond dissociation by LEE impact. Damages to plasmid DNA including crosslinks, SSBs, DSBs and the loss of the supercoiled configuration were analyzed by the electrophoresis. Base damages (BDs) occurring within two turns of DNA helix were detected by the treatment of E. coli base excision repair endonuclease (Nth and Fpg).