Abstract

Oxidative stress and oxidative damage play critical roles in the development of many tobacco-related diseases including heart and respiratory diseases, and cancers. We are testing the many aspects of free radical production and exposure in various tobacco products. We have recently developed methods for the direct, comprehensive, quantitative and reproducible assessment of free radicals in tobacco smoke by electron paramagnetic resonance spectroscopy (EPR). Using these standardized protocols, we have found high levels of radicals in a series of combustible tobacco products (e.g. small cigars, commercial and make-your-own cigarettes) and non-combustible products (e.g. electronic-cigarettes). We found large (>12-fold) variation in the production of radicals between product brands/types. We next conducted a pilot switching study, in which a total 14 subjects switched from their usual cigarette to a reduced oxidant cigarette for 2 weeks and smoking topography, and biomarkers of exposure (plasma cotinine) and oxidative stress/damage, including 8-hydroxydeoxyguanosine (8-OHdG, oxidative DNA damage) and 8-isoprostane (8-IsoP, lipid peroxidation) and oxidized:reduced glutathione (GSSG:GSH ratio, redox status) were analyzed before and after switching. A decline in all 3 biomarkers of oxidative stress was observed after 2 weeks, with 8-OHdG decreasing by 20% (P

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