DNA repair deficiency in peripheral blood lymphocytes of endometrial cancer patients with a family history of cancer.

Lyubov Buchynska,Olena Bilyk,Olga Brieieva,Nadiia Glushchenko,Ludmila Vorobyova

doi:10.1186/1471-2407-14-765

Abstract

BackgroundIndividual susceptibility to endogenous and/or exogenous DNA damage depends on DNA repair efficiency and can be evaluated using the comet assay with bleomycin as genotoxic agent. The aim of the study was to evaluate baseline and bleomycin-induced DNA damage and DNA repair capacity in peripheral blood lymphocytes (PBLs) of endometrial cancer (EC) patients considering a family history of cancer.MethodsDNA damage was analyzed in PBLs of 45 EC patients compared to a control group of 10 healthy women, using the comet assay. The level of DNA damage was determined by the% tail DNA.ResultsThe level of baseline DNA damage in PBLs of EC patients was significantly higher (% DNA in tail 9.31 ± 15.32) than in healthy women (% DNA in tail 3.41 ± 4.71) (P <0.01). PBLs of EC patients repaired less bleomycin-induced DNA damage (removed% DNA in tail 63.94 ± 20.92) than PBLs of healthy individuals (removed% DNA in tail 80.24 ± 3.03) (P <0.001). Efficiency of DNA repair in PBLs of EC patients depended on the family history of cancer. The amount of restored damaged DNA was significantly lower (removed% DNA in tail 36.24 ± 14.05%) in EC patients with a family history of cancer compared to patients with sporadic EC (removed% DNA in tail 64.91 ± 19.36%) (P <0.004).ConclusionsLymphocytes of EC patients are characterized by an increased basal level of DNA damage as well as deficiency in DNA repair. DNA repair is less efficient in PBLs of EC patients with a family history of cancer compared to patients with sporadic cancer.

Highlights

Individual susceptibility to endogenous and/or exogenous DNA damage depends on DNA repair efficiency and can be evaluated using the comet assay with bleomycin as genotoxic agent
The net bleomycininduced DNA damage was assessed by subtracting the basal% DNA in tail from the% DNA in tail obtained after incubating the peripheral blood lymphocytes (PBLs) with bleomycin
To determine the significance of hereditary factor for genetic instability in PBLs, we studied the level of baseline DNA damage, bleomycin sensitivity and DNA repair capacity in endometrial cancer (EC) patients in relation to a family history of cancer

Summary

Introduction

Individual susceptibility to endogenous and/or exogenous DNA damage depends on DNA repair efficiency and can be evaluated using the comet assay with bleomycin as genotoxic agent. A deficiency in DNA repair capacity leads to greater DNA damage mediated by genotoxic agents and may result in accumulated DNA damage. Both these factors exponentially contribute to increasing the risk for cancer through genomic instability [1,2,3]. These studies hypothesize that the level of genome damage in PBLs suggests an individual susceptibility to cancer [12,13,14]

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