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 sugge sted to be involved in carcinogenesis by oxidative modification of DNA . The urinary excretion rate of the oxidized nucleoside 8-oxo-7,8-dihy dro-2'-deoxyguanosine (8-oxodG) has been validated as a biomarker of t he rate of oxidative DNA modification with mechanistic relation to car cinogenesis. In cross-sectional studies, the urinary excretion rate of 8-oxodG has been shown to be elevated in smokers compared with non-sm okers. Purpose: In this randomised, controlled smoking cessation study , we investigated whether cigarette smoking per se causes oxidative DN A 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 th at were analysed for 8-oxodG content by high-pressure liquid chromatog raphy with electrochemical detection. The subjects randomized to smoki ng cessation were followed up after 26 weeks. Results: Four weeks of s moking 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 co ntinued 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/2 4 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 i n the quitters (P = 0.0085, ANCOVA), demonstrating the effect of smoki ng per se, A 23% (P < 0.005) decrease in 8-oxodG excretion rate was su stained for 26 weeks in 27 quitters who completed the study. Conclusio n: Smoking cessation significantly reduces the urinary excretion rate of 8-oxodG, giving direct and controlled evidence that cigarette smoki ng causes an increased rate of oxidative DNA modification. This could represent a mechanism by which tobacco smoke is carcinogenic.