title: 8-hydroxy-2'-deoxyguanosine of leukocyte DNA as a marker of oxidative stress in chronic hemodialysis patients.
abstract: In contrast to proteins and lipids, oxidative damage to DNA has not been well studied in patients undergoing hemodialysis (HD). We hypothesized that phagocytes are activated after blood-membrane contact during HD, and oxidants from metabolic activation can damage leukocyte DNA. To test this hypothesis, the 8-hydroxy-2'-deoxyguanosine (8-OHdG) content of leukocyte DNA was measured by high-performance liquid chromatography electrochemical detection method in 35 age- and sex-matched healthy subjects, 22 undialyzed patients with advanced renal failure, and 109 HD patients to assess the relation between oxidative DNA damage and complement-activating membranes, blood antioxidants, and iron status. Dialysis membranes were classified into complement-activating (cellulose; n = 55) and non-complement-activating (polymethylmethacrylate [PMMA]; n = 35; polysulfone [PS]; n = 19) membranes. We found increased oxidative stress in undialyzed and HD patients based on a decrease in plasma levels of ascorbate and alpha-tocopherol adjusted for blood lipid (alpha-tocopherol/lipid), serum albumin, and reduced glutathione levels in whole blood and an increase in oxidized glutathione levels in whole blood compared with controls (P < 0.001). The greatest 8-OHdG level in leukocyte DNA was in HD patients, followed by undialyzed patients and healthy controls (P < 0.001), and was significantly greater in HD patients using cellulose membranes than those using PMMA or PS membranes (P < 0.001). 8-OHdG levels correlated with plasma alpha-tocopherol/lipid (r = -0.314; P < 0.005), serum iron (r = 0. 446; P < 0.001), and transferrin saturation values (r = 0.202; P < 0.05) in the analysis of all HD patients. In a 6-week crossover study, 8-OHdG levels significantly decreased after the switch from cellulose to synthetic membranes for 2 weeks and increased after the shift from synthetic to cellulose membranes (P < 0.05). Iron metabolism indices and plasma alpha-tocopherol/lipid values did not change significantly in the study period. We conclude that 8-OHdG content in leukocyte DNA is a biomarker of oxidant-induced DNA damage in HD patients. Oxidative DNA damage is a consequence of uremia, further augmented by complement-activating membranes.
authors.affiliation: Institute of Clinical Medicine and the Department of Biochemistry and Center for Cellular and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: D C
authors.initials: DC
authors.lastname: Tarng
authors.forename: T P
authors.initials: TP
authors.lastname: Huang
authors.forename: Y H
authors.initials: YH
authors.lastname: Wei
authors.forename: T Y
authors.initials: TY
authors.lastname: Liu
authors.forename: H W
authors.initials: HW
authors.lastname: Chen
authors.forename: T
authors.initials: T
authors.lastname: Wen Chen
authors.forename: W C
authors.initials: WC
authors.lastname: Yang
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003167:Complement Activation; D018592:Cross-Over Studies; D004247:DNA / Q000737:chemistry*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000097:blood*; D005260:Female; D005978:Glutathione / Q000097:blood; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000235:genetics / Q000628:therapy; D007962:Leukocytes / Q000737:chemistry; D008297:Male; D008567:Membranes, Artificial; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics*; D006435:Renal Dialysis / Q000009:adverse effects
chemical_list: D015415:Biomarkers; D008567:Membranes, Artificial; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine; D005978:Glutathione