Urinary excretion of three nucleic acid oxidation adducts and isoprostane F(2)alpha 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 F(2)alpha (IsopF(2)alpha) 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 microg/g creatinine. IsopF(2)alpha 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 microg/g creatinine. There were significant correlations among all three nucleic acid adducts and between IsopF(2)alpha and both 5-OHmU and 8-OHdG. Many smokers and ex-smokers had high levels of either 5-OHmU excretion or IsopF(2)alpha excretion, but not both. We conclude that 5-OHmU and IsopF(2)alpha 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.
Harman
S Mitchell
SM
Kronos Longevity Research Institute, Phoenix, AZ, USA. harman@kronosinstitute.org
Liang
Lynn
L
Tsitouras
Panayiotis D
PD
Gucciardo
Frank
F
Heward
Christopher B
CB
Reaven
Peter D
PD
Ping
Wei
W
Ahmed
Alaa
A
Cutler
Richard G
RG
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D002853:Chromatography, Liquid; D018736:DNA Adducts / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine*; D005260:Female; D006151:Guanosine / Q000031:analogs & derivatives* / Q000652:urine*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017678:Sex Distribution; D012907:Smoking / Q000009:adverse effects / Q000378:metabolism*; D013936:Thymidine / Q000031:analogs & derivatives* / Q000652:urine*
D018736:DNA Adducts; D006151:Guanosine; C075750:8-epi-prostaglandin F2alpha; C046215:8-hydroxyguanosine; C018080:5-hydroxymethyl-2'-deoxyuridine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D015237:Dinoprost; D003849:Deoxyguanosine; D013936:Thymidine