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Contribution of Base Damages to the Molecular Radiosensitization Mechanism of Platinum Chemotherapeutic Drugs
Author(s) -
Cai Yanming,
Zhou Limei,
Gao Yingxia,
Liu Wenhui,
Shao Yu,
Zheng Yi
Publication year - 2019
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201803400
Subject(s) - dna , cisplatin , chemistry , oxaliplatin , dna damage , ku70 , biophysics , microbiology and biotechnology , cancer , biochemistry , biology , genetics , chemotherapy , colorectal cancer
The measurement of clustered damages in Pt‐chemotherapeutic‐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). The total DNA damages to Pt‐DNA complexes was found to be 350 ± 42, 296 ± 45 and 434 ± 46 ×10 −15 electron −1 molecule −1 , respectively, while the percentages of BDs in this total were 56%, 54% and 60%, respectively. Compared to unmodified DNA, binding of Pt‐drugs to DNA increased BDs by factors of 1.9, 1.6 and 2.6, respectively, which partly resulted in significant enhancements of potentially lethal lesions (i. e., crosslinks, double strand breaks (DSBs) and non‐DSB cluster damages). These results reveal the significant role that LEEs play in the formation of clustered DNA damages related to BDs, which are expected to contribute to the higher efficacy of cancer treatment by CRT with the Pt‐drugs investigated.