Urinary excretion of three nucleic acid oxidation adducts and isoprostane F₂α measured by liquid chromatography-mass spectrometry in smokers, ex-smokers, and nonsmokers

To assess novel liquid chromatography/mass spectrometric methods for measuring oxidative damage to nucleic acids and lipids, we compared urinary excretion of 8-hydroxy-2′-deoxyguanosine (8-OHdG), 5-hydroxymethyl- 2′-deoxyuridine (5-OHmU), and 8-hydroxyguanosine (8-OxoG), and an isoprostane, 8-iso-prostaglandin F₂α (IsopF₂α) in 234 healthy men (n = 113) and women (n = 121), 80 current smokers, 96 never-smokers), and 58 ex-smokers (no tobacco use for 3 years). The 8-OHdG and 8-OxoG did not differ significantly by group; 5-OHmU was higher in smokers, compared with ex- (p < .003) and never- (p < .0001) smokers and in ex- vs. never-smokers (p = .014) at, respectively, 13.5 ± 0.7, 11.3 ± 1.0, and 8.7 ± 0.3 μg/g creatinine. IsopF₂α was higher in smokers, compared with ex- (p = .007) and never-smokers (p < .0001) and in ex- vs. never- smokers (p = .002) at, respectively, 1.1 ± 0.10; 0.74 ± 0.07, and 0.51 ± 0.04 μg/g creatinine. There were significant correlations among all three nucleic acid adducts and between IsopF₂α and both 5-OHmU and 8-OHdG. Many smokers and ex-smokers had high levels of either 5-OHmU excretion or IsopF ₂α excretion, but not both. We conclude that 5-OHmU and IsopF₂α are more discriminating of oxidative stress from tobacco smoke than the other two compounds measured. Whether characteristic patterns of excretion of these indicators forecast differential disease risk should be explored in future research.