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Hydrated electrons induce the formation of interstrand cross-links in DNA modified by cisplatin adducts

Authors: Behmand BNoronha AMWilds CJMarignier JLMostafavi MWagner JRHunting DJSanche L


Affiliations

1 Groupe en sciences des radiations, Faculté de médicine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Québec, J1H 5N4, Canada.
2 Department of Chemistry and Biochemistry, Concordia University, Montréal, Québec, H4B1R6, Canada.
3 Centre de cinétique rapide ELYSE, Laboratoire de chimie physique, Université de Paris-Saclay 11, Orsay, France.

Description

Double-stranded oligonucleotides containing cisplatin adducts, with and without a mismatched region, were exposed to hydrated electrons generated by gamma-rays. Gel electrophoresis analysis demonstrates the formation of cisplatin-interstrand crosslinks from the cisplatin-intrastrand species. The rate constant per base for the reaction between hydrated electrons and the double-stranded oligonucleotides with and without cisplatin containing a mismatched region was determined by pulse radiolysis to be 7 × 109 and 2 × 109 M-1 s-1, respectively. These results provide a better understanding of the radiosensitizing effect of cisplatin adducts in hypoxic tumors and of the formation of interstrand crosslinks, which are difficult for cells to repair.


Keywords: anticancer drugsgel electrophoresisoligonucleotidepulse radiolysisradiotherapyrate constant


Links

PubMed: https://pubmed.ncbi.nlm.nih.gov/32211848/

DOI: 10.1093/jrr/rraa014