Effect of smoking cessation on oxidative DNA modification estimated by 8-oxo-7,8-dihydro-2'-deoxyguanosine excretion.

Background: Reactive oxygen species from, e.g. tobacco smoke are suggested to be involved in carcinogenesis by oxidative modification of DNA. The urinary excretion rate of the oxidized nucleoside 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) has been validated as a biomarker of the rate of oxidative DNA modification with mechanistic relation to carcinogenesis. In cross-sectional studies, the urinary excretion rate of 8-oxodG has been shown to be elevated in smokers compared with non-smokers. Purpose: In this randomised, controlled smoking cessation study, we investigated whether cigarette smoking per se causes oxidative DNA modification. Methods: Of the 182 healthy smokers included, 100 were randomized to quit smoking after baseline samples had been taken, and 82 were randomized to continue usual smoking, Before the start of the study and after 4 weeks, the subjects collected 24-h urine samples that were analysed for 8-oxodG content by high-pressure liquid chromatography with electrochemical detection. The subjects randomized to smoking cessation were followed up after 26 weeks. Results: Four weeks of smoking cessation resulted in a 21% decrease in 8-oxodG excretion rate (from mean +/- SD, 30.5 +/- 13.9 to 24.1 +/- 10.5 nmol/24 h, P < 0.001) in 58 quitters included in per-protocol data analysis. Sixty-five continued smokers included in per-protocol analysis showed a 9% decrease in 8-oxodG excretion rate (from 31.6 +/- 13.2 to 28.7 +/- 12.6 nmol/24 h, P = 0.026). After 4 weeks, the 8-oxodG excretion rate was 16% (95% confidence interval 4 to 28%) higher in the continued smokers than in the quitters (P = 0.0085, ANCOVA), demonstrating the effect of smoking per se, A 23% (P < 0.005) decrease in 8-oxodG excretion rate was sustained for 26 weeks in 27 quitters who completed the study. Conclusion: Smoking cessation significantly reduces the urinary excretion rate of 8-oxodG, giving direct and controlled evidence that cigarette smoking causes an increased rate of oxidative DNA modification. This could represent a mechanism by which tobacco smoke is carcinogenic.