Exocyclic DNA adducts and oxidative stress parameters: useful tools for biomonitoring exposure to aldehydes in smokers.

CONTEXT: Exocyclic DNA adducts have been shown to be potential biomarkers of cancer risk related to oxidative stress and exposure to aldehydes in smokers. In fact, aldehydes potentially arise from tobacco combustion directly and endogenously through lipid peroxidation. OBJECTIVE: This study aims to investigate the relationship between a profile of nine aldehydes-induced DNA adducts and antioxidant activities, in order to evaluate new biomarkers of systemic exposure to aldehydes. METHODS: Using our previously published UPLC-MS/MS method, adducts levels were quantified in the blood DNA of 34 active smokers. The levels of antioxidant vitamins (A, C and E), coenzyme Q10, ß-carotene, superoxide dismutase (SOD) and autoantibodies against oxidized low-density lipoprotein were measured. RESULTS: Adducts induced by tobacco smoking-related aldehydes were quantified at levels reflecting an oxidative production from lipid peroxidation. A significant correlation between SOD and crotonaldehyde-induced adducts (p = 0.0251) was also observed. ß-Carotene was negatively correlated with the adducts of formaldehyde (p = 0.0351) and acetaldehyde (p = 0.0413). Vitamin C tended to inversely correlate with acetaldehyde-induced adducts (p = 0.0584). CONCLUSION: These results are promising, and the study is now being conducted on a larger cohort with the aim of evaluating the impact of smoking cessation programs on the evolution of adducts profile and antioxidants activities.

Genotoxicity of aldehyde mixtures: profile of exocyclic DNA-adducts as a biomarker of exposure to tobacco smoke.

Electrophilic compounds present in humans, originating from endogenous processes or pollutant exposures, pose a risk to health though their reaction with nucleophilic sites in protein and DNA. Among this chemical class, aldehydes are mainly present in indoor air and they can also be produced by endogenous lipid peroxidation arising from oxidative stress. Known to be very reactive, aldehydes have the ability to form exocyclic adducts to DNA that, for the most if not repaired correctly, are mutagenic and by consequence potential agents involved in carcinogenesis. The aim of this work was to establish profiles of exocyclic DNA adducts induced by aldehyde mixtures, which could ultimately be considered as a genotoxic marker of endogenous and environmental aldehyde exposure. Adducts were quantified by an accurate, sensitive and validated ultra high performance liquid chromatography-electrospray ionization analytical method coupled to mass spectrometry in the tandem mode (UHPLC-ESI-MS/MS). We simultaneously measured nine exocyclic DNA adducts generated during the exposure in vitro of calf thymus DNA to different concentrations of each aldehyde along, as well as, to an equimolar mixture of these aldehydes. This approach has enabled us to establish dose-response relationships that allowed displaying the specific reactivity of aldehydes towards corresponding adducts formation. Profiles of these adducts determined in DNA of current smokers and non-smokers blood samples supported these findings. These first results are encouraging to explore genotoxicity induced by aldehyde mixtures and can furthermore be used as future reference for adductomic approaches.