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

Abstract

Background: 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 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.

Methods: DNA 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.

Results: The 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).

Conclusions: Lymphocytes 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.

Figure 1

Examples of DNA comets obtained by comet assay in peripheral blood lymphocytes of healthy individuals (A,C,E) and EC patients (B, D, F). A, B. Baseline DNA damages; C, D. DNA damage after bleomycin exposure; E, F. DNA damage remained after repair.

Figure 2

Bleomycin-induced DNA damage removed in PBLs of healthy individuals and EC patients.