title: Reference ranges of urinary biomarkers of oxidized guanine in (2'-deoxy)ribonucleotides and nucleic acids.
abstract: 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±13.6years; 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.
authors.affiliation: Laboratory of Industrial Toxicology, Department of Clinical Medicine, Nephrology, and Health Sciences, ISPESL-National Institute for Occupational Safety and Prevention, Research Center, University of Parma, Parma, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Andreoli
authors.forename: Antonio
authors.initials: A
authors.lastname: Mutti
authors.forename: Matteo
authors.initials: M
authors.lastname: Goldoni
authors.forename: Paola
authors.initials: P
authors.lastname: Manini
authors.forename: Pietro
authors.initials: P
authors.lastname: Apostoli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Palma
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000652:urine*; D002289:Carcinoma, Non-Small-Cell Lung; D002853:Chromatography, Liquid; D003367:Cotinine / Q000652:urine; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000652:urine; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000652:urine; D006151:Guanosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000652:urine; D006801:Humans; D008175:Lung Neoplasms; D008297:Male; D008875:Middle Aged; D009696:Nucleic Acids / Q000652:urine*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D012016:Reference Values; D012907:Smoking; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D015415:Biomarkers; D009696:Nucleic Acids; D006151:Guanosine; C046215:8-hydroxyguanosine; C024829:8-hydroxyguanine; D006147:Guanine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D003367:Cotinine; D010100:Oxygen