Konstantinos Fiotakis

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.

Persistent free radicals, heavy metals and PAHs generated in particulate soot emissions and residue ash from controlled combustion of common types of plastic

The production and use of polymeric materials worldwide has reached levels of 150 million tonnes per year, and the majority of plastic materials are discarded in waste landfills where are burned generating toxic emissions. In the present study we conducted laboratory experiments for batch combustion/burning of commercial polymeric materials, simulating conditions of open fire combustion, with the purpose to analyze their emissions for chemical characteristics of toxicological importance. We used common types of plastic materials: poly(vinyl chloride) (PVC), low and high density poly(ethylene) (LDPE, HDPE), poly(styrene) (PS), poly(propylene) (PP) and poly(ethylene terephthalate) (PET). Samples of particulate smoke (soot) collected on filters and residue solid ash produced by controlled burning conditions at 600-750 degrees C are used for analysis. Emissions of particulate matter, persistent free radicals embedded in the carbonaceous polymeric matrix, heavy metals, other elements and PAHs were determined in both types of samples. Results showed that all plastics burned easily generating charred residue solid ash and black airborne particulate smoke. Persistent carbon- and oxygen-centered radicals, known for their toxic effects in inhalable airborne particles, were detected in both particulate smoke emissions and residue solid ash. Concentrations of heavy metals and other elements (determined by Inductively Coupled Plasma Emission Spectrometry, ICP, method) were measured in the airborne soot and residue ash. Toxic heavy metals, such as Pb, Zn, Cr, Ni, and Cd were relatively at were found at low concentrations. High concentrations were found for some lithophilic elements, such as Na, Ca, Mg, Si and Al in particulate soot and residue solid ash. Measurements of PAHs showed that low molecular weight PAHs were at higher concentrations in the airborne particulate soot than in the residue solid ash for all types of plastic. Higher-ringed PAHs were detected at higher concentrations in the residue solid ash of PVC as compared to those from the other types of plastic. The open-air burning of plastic material and their toxic emissions is of growing concern in areas of municipal solid waste where open-fires occur intentionally or accidentally. Another problem is building fires in which victims may suffer severe smoke inhalation from burning plastic materials in homes and in working places.

Determination of Selective Quinones and Quinoid Radicals in Airborne Particulate Matter and Vehicular Exhaust Particles

Environmental Context.Fine and coarse airborne particulate matter (PM) has been linked to increases in respiratory diseases and lung cancer. PM contains a variety of compounds, such as metals, polycyclic aromatic hydrocarbons (PAHs), nitro-PAHs, and quinones adsorbed in a carbonaceous polymeric matrix. Although quinones are found in small amounts in PM, they are capable of redox cycling and in the presence of oxygen catalyse the generation of reactive oxygen species (ROS) in biological systems. ROS are responsible for the induction of oxidative stress, especially oxidative damage to cellular proteins and DNA. This paper investigated quantitatively selected quinones and hydroquinones by high performance liquid chromatography in various airborne PM samples. Also, we investigated the presence of persistent semiquinone radicals in solid samples and quinoid radicals in aqueous extracts of alkaline solution by electron paramagnetic resonance spectroscopy. Abstract.In recent years, there has been an increasing interest in the study of the health effects of respirable particulate matter (PM) because of its deposition in the human lungs and adverse health effects. Analysis of PM content focused on substances of toxicological importance, such as polycyclic aromatic hydrocarbons (PAHs), nitro-PAHs, aliphatic hydrocarbons, alkyl-substituted benzenes and naphthalenes, transition metals and various quinones. Recent studies shifted their attention to quinones and their toxicological role in PM. Quinones can be transformed into their semiquinones, which undergo redox cycling and reduce oxygen to produce reactive oxygen species (ROS) in biological systems, resulting in the induction of oxidative stress, especially oxidative damage to cellular components and DNA. In the present study, the presence of five quinones, 1,2-benzenediol (catechol) and 1,4-benzenediol (hydroquinone) in various PM samples was identified and measured quantitatively by high performance liquid chromatography. Mean concentrations of individual target quinones ranged from 15–140 ng mg–1 in diesel and gasoline exhaust particles to 1.5–60 ng mg–1 (or 150–1100 pg m–3) in airborne PM (total suspended particulates, PM aerodynamic diameter 10 μm, PM aerodynamic diameter 2.1 μm) samples. Precision (repeatability and reproducibility) varied from 5 to 15%. Also, examples of electron paramagnetic resonance spectra for the single broad unstructured signal are presented, corresponding to the persistent stable semiquinone radicals of solid samples of PM, and the formation of quinoid radicals in aqueous extracts of PM samples in air-saturated carbonate-buffered solution, pH 9.5–10.

Metal leachability, heavy metals, polycyclic aromatic hydrocarbons and polychlorinated biphenyls in fly and bottom ashes of a medical waste incineration facility

Medical waste from hospitals and other healthcare institutions has become an imperative environmental and public safety problem. Medical waste in Greece has become one of the most urgent environmental problems, because there are 14 000 tons produced annually, of which only a small proportion is incinerated. In the prefecture of Attica there is only one modern municipal medical waste incinerator (started 2004) burning selected infectious hospital waste (5—6 tons day— 1). Fly and bottom residues (ashes) are collected and stored temporarily in barrels. High values of metal leachability prohibit the landfilling of these ashes, as imposed by EU directives. In the present study we determined quantitatively the heavy metals and other elements in the fly and bottom ashes of the medical waste incinerator, by inductively coupled plasma emission spectrometry (ICP) and by energy dispersive X-ray analysis (EDAX). Heavy metals, which are very toxic, such as Pb, Cd, Ni, Cr, Cu and Zn were found in high concentrations in both fly and bottom ashes. Metal leachability of fly and bottom ashes by water and kerosene was measured by ICP and the results showed that toxic metals in both ashes, such as Pb, Cr, Cd, Cu and Zn, have high leaching values. These values indicate that metals can become soluble and mobile if ash is deposited in landfills, thus restricting their burial according to EU regulations. Analysis of polychlorinated biphenyls and polycyclic aromatic hydrocarbons in fly and bottom ashes showed that their concentrations were very low. This is the first known study in Greece and the results showed that incineration of medical waste can be very effective in minimizing the most hazardous and infectious health-care waste. The presence of toxic metals with high leachability values remains an important draw back of incineration of medical waste and various methods of treating these residues to diminish leaching are been considered at present to overcome this serious technical problem.

The Role of Stable Free Radicals, Metals and PAHs of Airborne Particulate Matter in Mechanisms of Oxidative Stress and Carcinogenicity

Ambient airborne particulate matter (PM) is considered as the most important pollutant for adverse health effects in the human respiratory system. PM is known to contain a large number of toxic and carcinogenic substances which in the lung’s alveoli cause oxidative stress, inflammation and cytotoxic damage leading to malignant neoplasms. Studies in recent years focused on transition metals, polycyclic aromatic hydrocarbons (PAH), stable quinoid and carbonaceous radicals. In the presence of oxygen and through redox reactions PM promote the production of reactive oxygen species (ROS), especially hydroxyl radicals (HO•), which are linked to lipid peroxidation and oxidative damage to peptides and cellular and mitochondrial DNA. In this study we investigated the most important mechanisms of ROS generation from airborne traffic-related PM, and exhaust soot from diesel and gasoline vehicles (DEP, GEP). Using Electron Paramagnetic Resonance (EPR) we examined the presence of persistent quinoid free radicals and we studied the direct production of superoxide anion (O 2 •− ), hydrogen peroxide (H2O2) and the damaging hydroxyl radicals (HO•) by PM extracts. Also, we examined by EPR the formation of oxidative damage to guanosine nucleobase by PM in aqueous phosphate buffer (pH 7.4). Experimental evidence shows that redox-active transition metals, persistent redox-cycling quinoids, and PAHs contained in the PM act synergistically, producing ROS. These ROS are considered the main mechanisms for the cytotoxic and carcinogenic potential of PM, leading to oxidative stress, pulmonary tissue injuries and DNA damage.

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.