title: Basal damage and oxidative DNA damage in children with chronic kidney disease measured by use of the comet assay.
abstract: One consequence of chronic kidney disease (CKD) is an elevated risk for cancer. There is sufficient evidence to conclude that there is an increased incidence of at least some cancers in kidney-dialysis patients. Cancer risk after kidney transplantation has mainly been attributed to immunosuppressive therapy. There are no data evaluating DNA damage in children with CKD, in dialysis patients, or following kidney transplantation. In this study, the comet assay and the enzyme-modified comet assay - with the use of endonuclease III (Endo III) and formamidopyrimidine glycosylase (FPG) enzymes - were conducted to investigate the basal damage and the oxidative DNA damage as a result of treatment in peripheral blood lymphocytes of children. Children at various stages of treatment for kidney disease, including pre-dialysis patients (PreD) (n=17), regular hemodialysis patients (HD) (n=15), and those that received kidney transplants (Tx) (n=17), comprised the study group. They were compared with age- and gender-matched healthy children (n=20) as a control group. Our results show that the %DNA intensity, a measure of basal damage, was significantly increased in children with CKD (mean ± SD) (5.22 ± 1.57) and also in each of the PreD, HD, and Tx groups [(4.92 ± 1.23), (4.91 ± 1.35), and (5.79 ± 1.94), respectively, vs the healthy children (2.74 ± 2.91) (p<0.001). Significant increases in oxidative DNA damage were only found in the FPG-sensitive sites for the PreD and Tx groups, compared with control and HD groups (p<0.05), suggesting that basal DNA damage was more evident for the PreD, HD, and Tx groups. The findings of the present study indicate a critical need for further research on genomic damage with different endpoints and also for preventive measures and improvements in treatment of pediatric patients, in order to improve their life expectancy.
authors.affiliation: Gazi University, Faculty of Pharmacy, Department of Toxicology, Ankara, Turkey.
authors.forename: Banu
authors.initials: B
authors.lastname: Aykanat
authors.forename: Gonca Cakmak
authors.initials: GC
authors.lastname: Demircigil
authors.forename: Kibriya
authors.initials: K
authors.lastname: Fidan
authors.forename: Necla
authors.initials: N
authors.lastname: Buyan
authors.forename: Kaan
authors.initials: K
authors.lastname: Gulleroglu
authors.forename: Esra
authors.initials: E
authors.lastname: Baskin
authors.forename: Umut Selda
authors.initials: US
authors.lastname: Bayrakci
authors.forename: Aylin
authors.initials: A
authors.lastname: Sepici
authors.forename: Bahar
authors.initials: B
authors.lastname: Buyukkaragoz
authors.forename: Hamdi
authors.initials: H
authors.lastname: Karakayali
authors.forename: Mehmet
authors.initials: M
authors.lastname: Haberal
authors.forename: Sema
authors.initials: S
authors.lastname: Burgaz
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002908:Chronic Disease; D020552:Comet Assay / Q000379:methods*; D004249:DNA Damage; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics* / Q000628:therapy; D016030:Kidney Transplantation; D008297:Male; D018384:Oxidative Stress; D006435:Renal Dialysis