DNA damage and repair capacity in patients with non-small cell lung cancer treated with polychemotherapy

Abstract

Introduction: In advanced stages of non-small cell lung cancer (NSCLC), treatment is based primarily on polychemotherapy. The sensitivity and the phenomena of chemoresistance to the treatments used depend, among other factors, on the functionality of the various DNA repair mechanisms.
Objective: To evaluate the effect of polychemotherapy with cisplatin and vinblastine on basal endogenous DNA damage, and the repair capacity of H₂O₂-induced damage in patients with advanced NSCLC.
Material and Methods: A descriptive study with a prospective longitudinal design was carried out. We included 15 patients with NSCLC, aged between 44 and 77 years, (stages IIIb-IV), treated with cisplatin and vinblastine in the Hospital Neumologico "Benefico Juridico", and 10 apparently healthy individuals (ages: 52-69 years) as control group. The alkaline variant of the comet assay was used to determine the endogenous basal DNA damage and its capacity to repair the damage induced with H₂O₂ in lymphocytes isolated from patients before and after treatment and controls.
Results: The patients had no alterations in the endogenous basal damage before treatment, but there was a reduced repair capacity of the damage induced in the DNA by the peroxide in comparison with the control subjects. After treatment, a significant increase in DNA damage was observed, as well as an increase in DNA repair efficiency.
Conclusions: The combined treatment of cisplatin and vinblastine in patients with NSCLC in advanced stages produced DNA damage and the efficiency of DNA repair increased. These genotoxicity markers could be used as predictors of response to this polychemotherapy regimen.

Keywords:DNA damage, DNA repair capacity, non-small cell lung cancer, cisplatin, vinblastine, Comet Assay.