Products of oxidative DNA damage and repair as possible biomarkers of susceptibility to lung cancer.

The broad spectrum of oxidative DNA damage biomarkers [urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OH-dGuo) and 8-hydroxyguanine (8-OH-Gua)] and the level of oxidative DNA damage and repair in leukocytes DNA were analyzed in three groups of subjects: (a) lung cancer patients [all smokers (n = 51)]; (b) healthy smokers with comparable smoking status (n = 26); and (c) healthy nonsmokers (n = 38). The mean level of 8-OH-Gua in urine samples of 38 healthy nonsmokers reached a value of 1.783 +/- 0.785 nmol/day/kg. This level was significantly lower than that in the urine of the two smoker groups (cancer patients and healthy smokers), in whom the levels reached values of 2.319 +/- 1.271 and 2.824 +/- 0.892 nmol/day/kg, respectively. Urinary excretion of 8-OH-dGuo was similar in all groups of subjects. The level of 8-OH-dGuo in DNA isolated from leukocytes of cancer patients was significantly higher than that in DNA isolated from the group of healthy smokers and nonsmokers (9.44 +/- 4.77 versus 7.20 +/- 2.83 and 5.88 +/- 2.47 molecules/10(6) deoxyguanosine, respectively). Repair activity of 8-OH-Gua, as estimated by the nicking assay, was significantly higher in blood leukocytes of healthy volunteers (44.6 +/- 20.21 and 37.54 +/- 13.43 pmol/h/mg protein for smokers and nonsmokers, respectively) than in the leukocytes of lung cancer patients (24.56 +/- 11.28 pmol/h/mg protein). Because oxidative DNA insult represented by urinary excretion of oxidative DNA lesions was similar in both groups of subjects with similar smoking status, it appears likely that a higher rate of generation of oxidative damage in cellular DNA of lung cancer patients is a result of deficiency of the repair mechanism(s) in this group.