Carcinogenesis, Vol 19, 347-351, Copyright © 1998 by Oxford University Press
H Prieme, S Loft, M Klarlund, K Gronbaek, P Tonnesen and HE Poulsen
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.
ARTICLES
Effect of smoking cessation on oxidative DNA modification estimated by 8-oxo-7,8-dihydro-2'-deoxyguanosine excretion
Department of Pharmacology, University of Copenhagen, Denmark.
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