title: A single subexcitation-energy electron can induce a double-strand break in DNA modified by platinum chemotherapeutic drugs.
abstract: The sensitization of malignant cells to ionizing radiation is the clinical rationale for the use of platinum-drug-based concurrent chemoradiotherapy (CCRT) for cancer treatment; however, the specific mechanisms of radiosensitization and their respective contributions still remain unknown. Biological mechanisms such as inhibition of DNA repair may contribute to the efficacy of CCRT; nevertheless, there is a dearth of information on the possible contribution of nanoscopic mechanisms to the generation of lethal DNA lesions, such as double-strand breaks (DSB). The present study demonstrates that the abundant near zero-eV (0.5 eV) electrons, created by ionizing radiation during radiotherapy, induce DSB in supercoiled plasmid DNA modified by platinum-containing anticancer drugs (Pt drugs), but not in unmodified DNA. They do so more efficiently than other types of radiation, including soft X-rays and 10 eV electrons. The formation of DSB by 0.5 eV electrons is found to be a single-hit process. These findings reveal insights into the radiosensitization mechanism of Pt drugs that can have implications for the development of optimal clinical protocols for platinum-based CCRT and the deployment of in situ sources of subexcitation-energy electrons (e.g., Auger electron-emitting radionuclides) to efficiently enhance DSB formation in DNA modified by Pt drugs in malignant cells.
authors.affiliation: Department of Nuclear Medicine & Radiobiology, Faculty of Medicine & Health Sciences, University of Sherbrooke, 3001, 12e Ave. Nord, Sherbrooke, QC, J1H 5N4 (Canada). Mohammad.Rezaee@USherbrooke.ca.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Rezaee
authors.forename: Elahe
authors.initials: E
authors.lastname: Alizadeh
authors.forename: Pierre
authors.initials: P
authors.lastname: Cloutier
authors.forename: Darel J
authors.initials: DJ
authors.lastname: Hunting
authors.forename: Léon
authors.initials: L
authors.lastname: Sanche
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D056831:Coordination Complexes / Q000737:chemistry* / Q000633:toxicity; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects / Q000528:radiation effects; D004583:Electrons; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D010984:Platinum / Q000737:chemistry*; D011839:Radiation, Ionizing
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D010984:Platinum; D004247:DNA
keywords: DNA damage; chemoradiation therapy; cisplatin; low-energy electrons; platinum drugs; radiosensitization