Tobacco Smoke: Involvement of Reactive Oxygen Species and Stable Free Radicals in Mechanisms of Oxidative Damage, Carcinogenesis and Synergistic Effects with Other Respirable Particles

Abstract: Tobacco smoke contains many toxic, carcinogenic and mutagenic chemicals, as well as stable and unstable free radicals and reactive oxygen species (ROS) in the particulate and the gas phase with the potential for biological oxidative damage. Epidemiological evidence established that smoking is one of the most important extrinsic factor of premature morbidity and mortality. The objective of this study was to investigate oxidative and carcinogenic mechanisms of tobacco and synergistic action with other respirable particles in the respiratory system of smokers. Electron Paramagnetic Resonance (EPR) and spin- trapping techniques were used to study stable free radicals in the cigarette tar, and unstable superoxide anion (O₂^·-) and hydroxyl (HO^·) radicals in the smoke Results showed that the semiquinone radical system has the potential for redox recycling and oxidative action. Further, results proved that aqueous cigarette tar (ACT) solutions can generate adducts with DNA nucleobases, particularly the mutagenic 8-hydroxy-2’-deoxyguanosine (a biomarker for carcinogenesis).Also, we observed synergistic effects in the generation of HO^·, through the Fenton reaction, with environmental respirable particles (asbestos fibres, coal dust, etc.) and ambient particulate matter (PM), such as PM₁₀, PM_2.5 and diesel exhaust particles (DEP). The highest synergistic effects was observed with the asbestos fibres (freshly grounded), PM_2.5 and DEP. Finally, we discuss results from our previous study of conventional cellulose acetate filters and “bio-filters” with hemoglobin impregnated activated carbon, which showed that these filters do not substantially alter the free radical content of smoke in the particulate and in the gaseous phase.