title: Gender-related reference intervals of urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine determined by liquid chromatography-tandem mass spectrometry in Serbian population.
abstract: OBJECTIVE
  Although there are many nucleobase modifications, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is one of the dominant form of oxidative modifications of DNA. Urinary 8-oxodG is potentially the best non-invasive biomarker of oxidative stress. Defining reference interval for urinary 8-oxodG is a prerequisite for its clinical use as biomarker.
  
  
  METHODS
  Reference population included 229 healthy Serbian adults (130 males and 99 females). The spot urinary 8-oxodG was determined using high performance liquid chromatography and tandem mass spectrometry (HPLC-MS/MS). Urinary creatinine was measured by the kinetic Jaffé method.
  
  
  RESULTS
  Analytical performances of the HPLC-MS/MS: CVs within and between-run variations were 5.6% and 2.6%; LOD and LOQ were 1.65 nmol/L and 3.30 nmol/L; mean recovery and relative accuracy were 96% and 97%. Creatinine level was higher in males than in females, but no gender difference in 8-oxodG level was observed. Upon the adjustment of 8-oxodG to creatinine (8-oxodG/creatinine), higher values were obtained in females (1.38 ± 0.65 nmol/mmol) than in males (1.05 ± 0.48 nmol/mmol). Distribution of 8-oxodG/creatinine in spot urine sample was log-normal and gender-related reference intervals (estimated as the 2.5th-97.5th percentiles) were 0.45-2.22 nmol/mmol for males, and 0.54-3.11 nmol/mmol for females. Body mass index (BMI) affects excretion of the 8-oxodG in males, independently of urinary creatinine, while in females it does not. Therefore, BMI might contribute to the gender-related differences of 8-oxodG/creatinine in spot urine samples.
  
  
  CONCLUSIONS
  This is the first established gender-related reference intervals of spot urinary 8-oxodG/creatinine. Our results contribute to the full validation of 8-oxodG as biomarker of oxidative stress.
authors.affiliation: University of Belgrade, Faculty of Pharmacy, Department of Medical Biochemistry, Belgrade, Serbia. aleksandra.topic1@gmail.com
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Topic
authors.forename: Djordje
authors.initials: D
authors.lastname: Francuski
authors.forename: Bojan
authors.initials: B
authors.lastname: Markovic
authors.forename: Marija
authors.initials: M
authors.lastname: Stankovic
authors.forename: Snezana
authors.initials: S
authors.lastname: Dobrivojevic
authors.forename: Sanja
authors.initials: S
authors.lastname: Drca
authors.forename: Dragica
authors.initials: D
authors.lastname: Radojkovic
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000652:urine; D005260:Female; D006801:Humans; D057230:Limit of Detection; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D012016:Reference Values; D055771:Serbia; D012737:Sex Factors; D012907:Smoking / Q000652:urine; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D015415:Biomarkers; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine