A single subexcitation-energy electron can induce a double-strand break in DNA modified by platinum chemotherapeutic drugs.
ChemMedChem
; 9(6): 1145-9, 2014 Jun.
Article
em En
| MEDLINE
| ID: mdl-24376113
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Platina
/
Radiação Ionizante
/
DNA
/
Complexos de Coordenação
/
Antineoplásicos
Tipo de estudo:
Guideline
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article