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

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, PM2.5 and diesel exhaust particles (DEP). The highest synergistic effects was observed with the asbestos fibres (freshly grounded), PM2.5 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

Pulmonary Oxidative Stress, Inflammation and Cancer: Respirable Particulate Matter, Fibrous Dusts and Ozone as Major Causes of Lung Carcinogenesis through Reactive Oxygen Species Mechanisms

Reactive oxygen or nitrogen species (ROS, RNS) and oxidative stress in the respiratory system increase the production of mediators of pulmonary inflammation and initiate or promote mechanisms of carcinogenesis. The lungs are exposed daily to oxidants generated either endogenously or exogenously (air pollutants, cigarette smoke, etc.). Cells in aerobic organisms are protected against oxidative damage by enzymatic and non-enzymatic antioxidant systems. Recent epidemiologic investigations have shown associations between increased incidence of respiratory diseases and lung cancer from exposure to low levels of various forms of respirable fibers and particulate matter (PM), at occupational or urban air polluting environments. Lung cancer increases substantially for tobacco smokers due to the synergistic effects in the generation of ROS, leading to oxidative stress and inflammation with high DNA damage potential. Physical and chemical characteristics of particles (size, transition metal content, speciation, stable free radicals, etc.) play an important role in oxidative stress. In turn, oxidative stress initiates the synthesis of mediators of pulmonary inflammation in lung epithelial cells and initiation of carcinogenic mechanisms. Inhalable quartz, metal powders, mineral asbestos fibers, ozone, soot from gasoline and diesel engines, tobacco smoke and PM from ambient air pollution (PM10 and PM2.5) are involved in various oxidative stress mechanisms. Pulmonary cancer initiation and promotion has been linked to a series of biochemical pathways of oxidative stress, DNA oxidative damage, macrophage stimulation, telomere shortening, modulation of gene expression and activation of transcription factors with important role in carcinogenesis. In this review we are presenting the role of ROS and oxidative stress in the production of mediators of pulmonary inflammation and mechanisms of carcinogenesis