Thomais Vlachogianni

8-hydroxy-2′ -deoxyguanosine (8-OHdG): A Critical Biomarker of Oxidative Stress and Carcinogenesis

There is extensive experimental evidence that oxidative damage permanently occurs to lipids of cellular membranes, proteins, and DNA. In nuclear and mitochondrial DNA, 8-hydroxy-2′ -deoxyguanosine (8-OHdG) or 8-oxo-7,8-dihydro-2′ -deoxyguanosine (8-oxodG) is one of the predominant forms of free radical-induced oxidative lesions, and has therefore been widely used as a biomarker for oxidative stress and carcinogenesis. Studies showed that urinary 8-OHdG is a good biomarker for risk assessment of various cancers and degenerative diseases. The most widely used method of quantitative analysis is high-performance liquid chromatography (HPLC) with electrochemical detection (EC), gas chromatography-mass spectrometry (GC-MS), and HPLC tandem mass spectrometry. In order to resolve the methodological problems encountered in measuring quantitatively 8-OHdG, the European Standards Committee for Oxidative DNA Damage was set up in 1997 to resolve the artifactual oxidation problems during the procedures of isolation and purification of oxidative DNA products. The biomarker 8-OHdG or 8-oxodG has been a pivotal marker for measuring the effect of endogenous oxidative damage to DNA and as a factor of initiation and promotion of carcinogenesis. The biomarker has been used to estimate the DNA damage in humans after exposure to cancer-causing agents, such as tobacco smoke, asbestos fibers, heavy metals, and polycyclic aromatic hydrocarbons. In recent years, 8-OHdG has been used widely in many studies not only as a biomarker for the measurement of endogenous oxidative DNA damage but also as a risk factor for many diseases including cancer.

Airborne particulate matter and human health: toxicological assessment and importance of size and composition of particles for oxidative damage and carcinogenic mechanisms.

Air pollution has been considered a hazard to human health. In the past decades, many studies highlighted the role of ambient airborne particulate matter (PM) as an important environmental pollutant for many different cardiopulmonary diseases and lung cancer. Numerous epidemiological studies in the past 30 years found a strong exposure-response relationship between PM for short-term effects (premature mortality, hospital admissions) and long-term or cumulative health effects (morbidity, lung cancer, cardiovascular and cardiopulmonary diseases, etc). Current research on airborne particle-induced health effects investigates the critical characteristics of particulate matter that determine their biological effects. Several independent groups of investigators have shown that the size of the airborne particles and their surface area determine the potential to elicit inflammatory injury, oxidative damage, and other biological effects. These effects are stronger for fine and ultrafine particles because they can penetrate deeper into the airways of the respiratory tract and can reach the alveoli in which 50% are retained in the lung parenchyma. Composition of the PM varies greatly and depends on many factors. The major components of PM are transition metals, ions (sulfate, nitrate), organic compound, quinoid stable radicals of carbonaceous material, minerals, reactive gases, and materials of biologic origin. Results from toxicological research have shown that PM have several mechanisms of adverse cellular effects, such as cytotoxicity through oxidative stress mechanisms, oxygen-free radical-generating activity, DNA oxidative damage, mutagenicity, and stimulation of proinflammatory factors. In this review, the results of the most recent epidemiological and toxicological studies are summarized. In general, the evaluation of most of these studies shows that the smaller the size of PM the higher the toxicity through mechanisms of oxidative stress and inflammation. Some studies showed that the extractable organic compounds (a variety of chemicals with mutagenic and cytotoxic properties) contribute to various mechanisms of cytotoxicity; in addition, the water-soluble faction (mainly transition metals with redox potential) play an important role in the initiation of oxidative DNA damage and membrane lipid peroxidation. Associations between chemical compositions and particle toxicity tend to be stronger for the fine and ultrafine PM size fractions. Vehicular exhaust particles are found to be most responsible for small-sized airborne PM air pollution in urban areas. With these aspects in mind, future research should aim at establishing a cleared picture of the cytotoxic and carcinogenic mechanisms of PM in the lungs, as well as mechanisms of formation during internal engine combustion processes and other sources of airborne fine particles of air pollution.

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.

Bioactive Natural Substances from Marine Sponges: New Developments and Prospects for Future Pharmaceuticals

In the last decades researchers of natural products chemistry focused their research in a wide variety of bioactive compounds from marine species. Marine sponges (Porifera) have been ranked very high in the priority of natural product research because the discovery of a wide range of bioactive chemical components and secondary metabolites with potential pharmaceutical applications gave promising results. These discoveries have attracted the attention of pharmaceutical chemistry experts, cell biologists, chemists of natural products and medical practitioners. Since the 1950s, when a number of the first publications appeared in the scientific literature, some bioactive natural chemicals from marine sponges gave successful examples of pharmaceuticals. Initial experimental results suggest that sponges have the potential to provide future drugs against important diseases, such as cancer, a range of viral diseases, malaria, and inflammations. At the same time scientists studied the molecular mode of action of most sponge-derived metabolites and their mechanism of action were elucidated for their therapeutic potential in a variety of diseases. This review aims at describing some of the most highly cited reviews of the last decade on sponge-derived bioactive compounds and the most promising substances extracted and isolated from marine sponges for pharmaceutical applications. The review is covering mainly new developments of the last five years in the field of marine sponge metabolite research and important findings for bioactive compounds from in vitro, in vivo and clinical studies for therapeutic drug applications.

Plant Polyphenols: Recent Advances in Epidemiological Research and Other Studies on Cancer Prevention

Abstract Plant polyphenols are considered among the most abundant phytochemicals that are present in human diets, and their regular consumption has been associated with reduced risk of a number of chronic diseases, including cancer, and cardiovascular and neurodegenerative disorders. In the past decades, plant polyphenols have drawn increasing scientific attention due to their potent antioxidant and other properties and their marked effects in the prevention of various oxidative stress-associated diseases. Recently, the polyphenolic extracts from different plants have become a major area of health- and medical-related research. This review provides an update and comprehensive overview of various plant polyphenolic compounds, and the quantification of their antioxidant properties, anticancer activities, and therapeutic effects. Also, the review discusses the current scientific knowledge of various plant polyphenols to inhibit tumorigenesis in animal models and to modulate cell signaling pathways involved in inflammation and the development of malignant tumors, and related biochemical interventions in cell function under both normal and pathological conditions. We present in vitro and in vivo studies (in experimental animals) in which polyphenols showed increased anticancer potential. Also, numerous epidemiological research data and findings from human intervention studies, as well preclinical studies supporting cancer prevention mechanisms. Lastly, we present recent clinical trials for anticancer action of certain polyphenols that showed promising anticancer and therapeutic properties.

Potential toxicity and safety evaluation of nanomaterials for the respiratory system and lung cancer

Engineered nanomaterials (ENMs) are a diverse group of materials finding increasing use in manufacturing, computing, food, pharmaceuticals, and biomedicine due to their very small size and exceptional properties. Health and safety concerns for ENMs have forced regulatory agencies to consider preventive measures and regulations for workers’ health and safety protection. Respiratory system toxicity from inhalable ENMs is the most important concern to health specialists. In this review, we focus on similarities and differences between conventional microparticles (diameters in mm and μm), which have been previously studied, and nanoparticles (sizes between 1 and 100 nm) in terms of size, composition, and mechanisms of action in biological systems. In past decades, respirable particulate matter (PM), asbestos fibers, crystalline silicate, and various amorphous dusts have been studied, and epidemiological evidence has shown how dangerous they are to human health, especially from exposure in working environments. Scientific evidence has shown that there is a close connection between respirable PM and pulmonary oxidative stress through the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). There is a close connection between oxidative stress in the cell and the elicitation of an inflammatory response via pro-inflammatory gene transcription. Inflammatory processes increase the risk for lung cancer. Studies in vitro and in vivo in the last decade have shown that engineered nanoparticles (ENPs) at various doses can cause ROS generation, oxidative stress, and pro-inflammatory gene expression in the cell. It is assumed that ENPs have the potential to cause acute respiratory diseases and probably lung cancer in humans. The situation regarding chronic exposure at low doses is more complicated. The long-term accumulation of ENPs in the respiratory system cannot be excluded. However, at present, exposure data for the general public regarding ENPs are not available.