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

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/μmolcreat) 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 (pb0.005) and with urinary creatinine (pb0.0001). Males excreted significantly higher concentrations of 8-oxoGua than females (pb0.0001). 8-OxoGua and 8-oxoGuo showed a positive association with age (pb0.001), 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 (pb0.0001) and of both 8-oxoGuo and 8-oxoGua in females (pb0.0001). 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 (pb0.0001 for both) compared to the referent population.