AIR POLLUTION – MONITORING MODELLING AND HEALTH

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312 Air Pollution <strong>–</strong> Monitoring, Modelling and Health Fig. 6. Hypothetical cyto-toxicological effects of nano-particles range from membrane peroxidation (a), once incorporated formation of reactive oxygen species (ROS) (b), activation of cell-receptors (c), triggering unnecessary cell-metabolic functions, activate expression of inflammatory responses (d), interaction with organelles, such a mitochondria (e), disruption of the electron transport chain (f), interaction with the DNA itself (g) and unfolding genotoxic potential by formation of DNA adducts (h).(modified after Oberdörster et al., 2007) Both the particles together with the adhered organic fraction and the consecutively induced oxidative stress can activate cell receptors (step “c”) - thereby exploiting the energy reservoir of cells for the induction of appropriate compensatory pathways, which trigger several intracellular signalling cascades. These cascades, along with transcription factors activate the expression of pro-inflammatory genes (steps “d”). Apart from interfering with intracellular communication pathways, nano-particles may also enter the cytosol from where they can access mitochondria (steps “e, f”) and disrupt normal electron transport, leading to additional oxidative stress (step “f”). Translocation of nano-aerosols into the nucleus may also occur where they interact with the genetic material (step “g”). Eventually, lipid peroxide-derived products can form DNA adducts, which may lead to genotoxicity and mutagenesis (step “h”). In less severe cases, the cell may enter the apoptotic pathway, thereby inducing premature cell death. (Elder et al., 2000) However, apoptosis leaves behind cellular debris together with a toxic particle load that requires clean-up by other cells. As outlined in Figure 6 (step “g”), genotoxic effects are known to occur also upon MEP exposure as this kind of aerosol induces structural aberrations of chromosomes, formation of micronuclei and DNA adducts. The described mutagenicity seems to be related to PAHs adhered to the surface of DEPs/MEPs. (Cheng et al., 2004) Apart from ROS-mediated activity (step “b”), oxidative DNA damages, such as strand breaks, are associated with the cocktail of UFPs and organic pollutants, e.g. benzene, in ambient air. (Cheng et al., 2004; Avogbe et al., 2005) These
Exposure to Nano-Sized Particles and the Emergence of Contemporary Diseases with a Focus on Epigenetics 313 DNA damages have been observed for respiratory as well as for gastrointestinal uptake of UFPs. (Avogbe et al., 2005; Dybdahl et al., 2003) The encountered genotoxity is apparently induced by intracellular ROS, since observed adverse effects were reduced by pre-treatment of cells with anti-oxidants. However, the extent of attenuation depends on the applied anti-oxidant and the protective effects were not complete. Organic fractions of DEPs and MEPs induced ROS are involved in the formation of DNA adducts, e.g. 8-hydroxy-deoxy-guanosine (8- OHdG), at least in the mouse model. This modification is considered a pro/e?-mutagenic lesion. (Cheng et al., 2004; Nagashima et al., 1995) Beside superoxide, also hydroxyl-radicals were formed when challenging mice with DEPs. (Nagashima et al., 1995) Nevertheless, PAHs have to be metabolized into their active forms via the P450-1A1 pathway. Additionally, MEPs contain constituents, which possess direct mutagenic potential and circumvent ROS formation. (Cheng et al., 2004) Furthermore, a genetic pre-disposition has to be considered, since genetic polymorphism in protective protein systems, e.g. glutathione S-transferase, glutathione peroxidase and NAD(P)H:quinone oxireductase-1 seem to be involved as well. (Avogbe et al., 2005) As mentioned before, organic chemicals adhered to DEPs are apparently directly involved in the formation of reactive nitrogen oxygen species (RNOS) and thus the induction of oxidative stress. Halogenated hydrocarbons and PAHs can induce phase-I drug metabolizing enzymes in alveolar macrophages and epithelial cells, such as cytochrome P450-1A1, which in turn degrade PAHs to redox active metabolites, e.g. quinones and phenols. (Nel et al., 1998; Devouassoux et al., 2002) Production of ROS has been related to the interaction between quinones and DEPs with P450 reductase. (Kumagai et al., 1997) Quinones will then contribute to ROS formation and macrophage activation. (Nel et al., 1998; Devouassoux et al., 2002) Benzo- [a]-pyrene (B[a]P) attached to black carbon enhanced the tumor necrosis factor- (TNF-) release of macrophages. Evidently, carbon particles with adhered organic compounds are endocytosed and PAHs get activated by intracellular ROS. (Kocbach et al., 2008) The increase in transcription induced by PAHs has been postulated to be promoted by a cytoplasmatic aryl hydrocarbon receptor (AhR), acting as a nuclear transporter/DNA binding protein PAH complex. Once released from DEPs, PAHs enter adjacent cells due to their hydrophobicity and adhere to the PAH ligand binding part of AhR which is then translocated to the nucleus. There, a heterodimer is created between the AhR and a nuclear translocator. This heterodimer binds to response sequences situated upstream of the target genes promoting e.g. the expression of plasminogen activator inhibitor and interleukin-1 (IL-1), which would explain the modulating effects of PAHs upon expression. Beside, signalling via AhR also Ca ++ depending pathways have been discussed as intracellular transmittance channels. (Takenaka et al., 1995; Fahy et al., 1999) Since NO-pathways induce Ca ++ release to regulate neuronal function, interference via nano-particles adversely affect Ca ++ release, and ultimately synaptic plasticity. (Kakizawa et al., 2011) As mentioned before, the expression of several enzymatic systems, e.g. the P450-1A1 cytochrome system, are induced. The latter metabolizes PAHs to electrophilic epoxides, which are mutagenic and can interact with DNA. Since 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is not metabolized by this system, alternative pathways are likely to co-exist. (Takenaka et al., 1995) 1.6 Short term exposure to airborne pollutants Studies have shown a decrease in pulmonary function associated with short-term exposure to UFPs. These decrements in lung function appear to persist for several weeks
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AIR POLLUTION - MONITORING, MODELLI
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Contents Preface IX Chapter 1 Urban
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Preface This book provides a compre
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2 Air Pollution - Monitoring, Model
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10 Air Pollution - Monitoring, Mode
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AIR POLLUTION – MONITORING MODELLING AND HEALTH

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