Unknown

Dataset Information

0

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.

SUBMITTER: Rezaee M 

PROVIDER: S-EPMC4623762 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

A single subexcitation-energy electron can induce a double-strand break in DNA modified by platinum chemotherapeutic drugs.

Rezaee Mohammad M   Alizadeh Elahe E   Cloutier Pierre P   Hunting Darel J DJ   Sanche Léon L  

ChemMedChem 20131204 6


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 generat  ...[more]

Similar Datasets

| S-EPMC4001069 | biostudies-literature
| S-EPMC3213282 | biostudies-literature
| S-EPMC8599755 | biostudies-literature
| S-EPMC3755766 | biostudies-literature
| S-EPMC7457334 | biostudies-literature
| S-EPMC7051178 | biostudies-literature
| S-EPMC2993650 | biostudies-literature
| S-EPMC5547995 | biostudies-literature
| S-EPMC9309806 | biostudies-literature
| S-EPMC2807415 | biostudies-other