Base excision repair capacity in chronic renal failure patients undergoing hemodialysis treatment

Abstract

The aim of this study was to determine if the differences observed in the levels of DNA damage in a group of patients suffering from chronic renal failure are due to differences in the repair capability. DNA damage was initially measured with the comet assay in 106 hemodialysis patients. A selected group of 21 patients representing high (ten patients) and low (11 patients) levels of DNA damage were obtained for determination of base excision repair capacity. This was measured in an in vitro assay where protein extracts from lymphocytes were incubated with a substrate of DNA containing 8-oxoguanine, and the rate of incision was measured with the comet assay. Patients with high levels of genomic damage showed, as an average, significantly lower repair capacity (12·73 ± 1·84) in comparison with patients with low levels of genomic damage (18·13 ± 1·13). Nevertheless, the correlation coefficient between repair ability and levels of genomic damage was found to be only close to the significance value (r:-0·423, p: 0·056). Although DNA damage was clearly related to time on hemodialysis, base excision repair capacity was not. This is one of the few studies providing information on the repair capacity of chronic renal failure patients undergoing hemodialysis. As a summary, our results would indicate that DNA damage levels are in part associated to the repair capacity of the patients, and this repair capacity is not associated with the duration of hemodialysis treatment.

Comet assay to measure DNA repair: approach and applications

“…Base excision repair has been assessed in patients suffering chronic renal failure, showing no association between BER activity and duration of hemodialysis (Stoyanova et al, 2014). Slyskova et al (2012) determined BER and NER activities in tumors from colorectal cancer patients and observed that the activities of both pathways did not differ from those of healthy adjacent tissue.…”

DNA damage in kidney transplant patients. Role of organ origin

“…These studies would support our findings showing over time increases in the levels of genetic damage in KT patients. It should be remembered our previous findings showing that CKD patients present genomic instability [Rodríguez‐Ribera et al, ] and deficiencies in base excision repair [Stoyanova et al, ]. This genetic susceptibility, together with potential exposure to genotoxic agents (including immunosuppressors), would explain the tendency to accumulate genetic damage in KT patients over time.…”

An optimized comet-based in vitro DNA repair assay to assess base and nucleotide excision repair activity

“…In studies investigating DNA repair activity in relation to human diseases, the comet-based in vitro DNA repair assay has been used only rarely, mainly on peripheral blood mononuclear cells (PBMC) of study subjects (e.g., patients suffering chronic renal failure 42 , patients with lung 43 and colorectal cancer 44,45 ), but also on biopsies from tumour and adjacent non-tumour tissue from colorectal cancer patients 19,46 .…”