title: Increased oxidative damage to peripheral blood leukocyte DNA in chronic peritoneal dialysis patients.
abstract: This study focuses on the extent of oxidative DNA damage in peripheral blood leukocytes of chronic peritoneal dialysis (CPD) patients. 8-Hydroxy 2'-deoxyguanosine (8-OHdG) contents in peripheral leukocyte DNA were measured by an HPLC-electrochemical detection method in 24 age- and sex-matched healthy subjects, 22 nondialyzed patients with advanced renal failure, and 42 CPD patients. Mean 8-OHdG content was the highest in CPD patients, followed by the nondialyzed patients, and then by the healthy subjects (19.4 versus 11.9 versus 8.3/10(6) dG; ANOVA P < 0.001). In nondialyzed subjects, peripheral leukocyte 8-OHdG contents inversely correlated with renal creatinine clearance (r = -0.772; P < 0.001). Deficiency of blood antioxidants in CPD and nondialyzed patients was expressed by the lower plasma levels of ascorbate, cholesterol-standardized alpha-tocopherol and whole-blood reduced glutathione, and the higher levels of whole-blood oxidized glutathione as compared with healthy subjects (ANOVA P < 0.05). Mean serum ferritin and iron levels and transferrin saturation were higher in the CPD patients than those in the nondialyzed patients and controls (ANOVA P < 0.05). Flow cytometric analyses of intracellular reactive oxygen species production of peripheral leukocytes showed that spontaneous production by granulocytes, as well as phorbol-12-myristate-13-acetate (PMA)-induced production by granulocytes, lymphocytes and monocytes, were the highest from CPD patients, followed by nondialyzed patients, and then by the healthy subjects (ANOVA P < 0.05). Forward stepwise multiple regression disclosed that uremia, PD treatment, spontaneous and PMA-induced reactive oxygen species production in leukocytes, and serum iron were the independent determinants of peripheral leukocyte 8-OHdG content (R(2) = 0.769; P < 0.001). In conclusion, profound increased 8-OHdG levels in peripheral leukocyte DNA occur in the course of chronic renal failure, gradually increase with its progression, and are further exacerbated by PD treatment.
authors.affiliation: Institute of Clinical Medicine, Faculty of Medicine, Department of Biochemistry, and Center for Cellular and Molecular Biology, National Yang-Ming University, Taipei, Taiwan. dctarng@vghtpe.gov.tw
authors.forename: Der-Cherng
authors.initials: DC
authors.lastname: Tarng
authors.forename: Tzen
authors.initials: T
authors.lastname: Wen Chen
authors.forename: Tung-Po
authors.initials: TP
authors.lastname: Huang
authors.forename: Chiu-Lan
authors.initials: CL
authors.lastname: Chen
authors.forename: Tsung-Yun
authors.initials: TY
authors.lastname: Liu
authors.forename: Yau-Huei
authors.initials: YH
authors.lastname: Wei
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000704:Analysis of Variance; D000975:Antioxidants / Q000032:analysis; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D002851:Chromatography, High Pressure Liquid; D003430:Cross-Sectional Studies; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000097:blood*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy; D007962:Leukocytes / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D011446:Prospective Studies
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine