Reference ranges of urinary biomarkers of oxidized guanine in (2′-deoxy)ribonucleotides and nucleic acids

• Published in: Free radical biology & medicine 2011-01, Vol.50 (2), p.254-261
• Main Authors: Andreoli, Roberta, Mutti, Antonio, Goldoni, Matteo, Manini, Paola, Apostoli, Pietro, De Palma, Giuseppe
• Format: Article
• Language: English
• Subjects: 8-Oxo-7,8-dihydro-2′-deoxyguanosine; 8-Oxo-7,8-dihydroguanine; 8-Oxo-7,8-dihydroguanosine; Adult; Age Factors; Aged; Aged, 80 and over; biomarkers; Biomarkers - urine; Carcinoma, Non-Small-Cell Lung; chemotherapy; Chromatography, Liquid; cotinine; Cotinine - urine; creatinine; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - chemistry; Deoxyguanosine - urine; Female; females; Free radicals; guanine; Guanine - analogs & derivatives; Guanine - chemistry; Guanine - urine; Guanosine - analogs & derivatives; Guanosine - chemistry; Guanosine - urine; Humans; linear models; liquid chromatography; Lung Neoplasms; Male; males; Middle Aged; nucleic acids; Nucleic Acids - urine; occupational exposure; oxidants; oxidation; Oxidation-Reduction; Oxygen - metabolism; patients; Reference ranges; Reference Values; regression analysis; ribonucleotides; Smoking; smoking (habit); Tandem Mass Spectrometry; Urine; Young Adult
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2010.11.009

This study was aimed at defining the reference ranges for biomarkers of oxidized guanine in (2′-deoxy)ribonucleotides and nucleic acids from a large Italian sample. We recruited 300 healthy subjects (150 males; mean age 44.1 ± 13.6 years; 26% smokers) without any known exposure to occupational oxidizing agents. They were asked to provide a spot urine sample, on which the following markers were determined by liquid chromatography–tandem mass spectrometry: 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo), 8-oxo-7,8-dihydroguanosine (8-oxoGuo), 8-oxo-7,8-dihydroguanine (8-oxoGua), and cotinine. The reference ranges, estimated as the 5th–95th percentiles of creatinine-normalized values (pmol/μmol creat) were 0.7–4.2, 0.9–4.7, and 5.6–120.7 for 8-oxodGuo, 8-oxoGuo, and 8-oxoGua, respectively. Oxidation biomarkers were correlated with one another ( p < 0 .005) and with urinary creatinine ( p < 0 .0001). Males excreted significantly higher concentrations of 8-oxoGua than females ( p < 0 .0001). 8-OxoGua and 8-oxoGuo showed a positive association with age ( p < 0 .001), also after stratification by gender. Multiple linear regression models including urinary creatinine concentration, age, and smoking habit as independent variables showed a significant effect of age, but not of smoking, on the levels of 8-oxoGuo in males ( p < 0 .0001) and of both 8-oxoGuo and 8-oxoGua in females ( p < 0 .0001). A preliminary assessment in a small group ( n = 25) of patients affected by advanced non-small-cell lung cancer and receiving platinum-based chemotherapy showed significantly higher values of both 8-oxoGuo and 8-oxodGuo ( p < 0.0001 for both) compared to the referent population.