Reduction in oxidatively generated DNA damage following smoking cessation

BACKGROUND: Cigarette smoking is a known cause of cancer, and cancer may be in part due to effects of oxidative stress. However, whether smoking cessation reverses oxidatively induced DNA damage unclear. The current study sought to examine the extent to which three DNA lesions showed significant reductions after participants quit smoking. METHODS: Participants (n = 19) in this study were recruited from an ongoing 16-week smoking cessation clinical trial and provided blood samples from which leukocyte DNA was extracted and assessed for 3 DNA lesions (thymine glycol modification [d(T(g)pA)]; formamide breakdown of pyrimidine bases [d(T(g)pA)]; 8-oxo-7,8-dihydroguanine [d(G(h))]) via liquid chromatography tandem mass spectrometry (LC-MS/MS). Change in lesions over time was assessed using generalized estimating equations, controlling for gender, age, and treatment condition. RESULTS: Overall time effects for the d(T(g)pA) (χ(2)(3) = 8.068, p < 0.045), d(P(f)pA) (χ(2)(3) = 8.477, p < 0.037), and d(G(h)) (χ(2)(3) = 37.599, p < 0.001) lesions were seen, indicating levels of each decreased significantly after CO-confirmed smoking cessation. The d(T(g)pA) and d(P(f)pA) lesions show relatively greater rebound at Week 16 compared to the d(G(h)) lesion (88% of baseline for d(T(g)pA), 64% of baseline for d(P(f)pA), vs 46% of baseline for d(G(h))). CONCLUSIONS: Overall, results from this analysis suggest that cigarette smoking contributes to oxidatively induced DNA damage, and that smoking cessation appears to reduce levels of specific damage markers between 30-50 percent in the short term. Future research may shed light on the broader array of oxidative damage influenced by smoking and over longer durations of abstinence, to provide further insights into mechanisms underlying carcinogenesis.