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Oxidative stress and changed gene expression profiles in fiber-/particle-induced carcinogenesis

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  • Patanjali Research Institute

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KEYWORDS Fibers; metals; gene expression; oxidative stress; cancer ABSTRACT Exposure to ambient air pollution (particles, fibres) is associated with pulmonary diseases and cancer. The mechanisms of induced health effects are believed to involve inflammation and oxidative stress. Oxidative stress mediated by airborne particles and/or fibres may arise from direct generation of reactive oxygen species (ROS) from the surface of particles/fibres, soluble compounds such as transition metals or organic compounds, and activation of inflammatory cells capable of generating ROS and reactive nitrogen species (RNS). Generation of ROS/RNS can directly cause covalent modifications to DNA or they can initiate the formation of genotoxic lipid hydroperoxides. The resulting oxidative DNA damage can lead to changed gene expression such as upregulation of tumor promoters and downregulation of tumor suppressor genes and thus may be implicated in cancer development. The present review describes the important role of free radicals in particle-/fibre- induced cellular damage, the interaction of ROS with target molecules, especially with DNA, and the modulation of specific genes and transcription factor caused by oxidative stress.
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... Excessive radical production and/or decreased antioxidants may lead to a condition called oxidative stress (14). Oxidative stress significantly impact multiple cellular pathways, that can lead Bas (16) and oxidative deterioration of poly unsaturated lipid that lead to lipid peroxidation (17), thus malondialdehyde (MDA) a lipid peroxidative product is used as an indicator of oxidative stress in cell and tissues. Hydrogen peroxide is one of the primary oxidants in biological system, it is lipid soluble and thus able to diffuse easily through biological membrane and reacting other cellular compartments, and induces damage to the cell membrane and decrease cell viability, furthermore, producing cellular injury especially if it become converted to the highly reactive OH ( 18,19). ...
... •is converted by the antioxidant enzyme superoxide dismutase (SOD) into hydrogen peroxide (H 2 O 2 ) and singlet oxygen. 11 SOD is the first enzymatic line of the antioxidant defense system, which scavenges superoxide radicals and prevents lipid peroxidation of the cellular membrane. Antioxidant enzymes are supported by nonenzymatic antioxidants and the total antioxidant capacity (TAC) is often used to estimate the overall antioxidative status in cells. ...
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Titanium dioxide (TiO2) nanoparticles (NPs) are manufactured worldwide for a variety of engineering and bioengineering applications. TiO2NPs are frequently used as a material for orthopedic implants. However, to the best of our knowledge, the biocompatibility of TiO2NPs and their effects on osteoblast cells, which are responsible for the growth and remodeling of the human skeleton, have not been thoroughly investigated. In the research reported here, we studied the effects of exposing hFOB 1.19 human osteoblast cells to TiO2NPs (5-15 nm) for 24 and 48 hours. Cell viability, alkaline phosphatase (ALP) activity, cellular uptake of NPs, cell morphology, superoxide anion (O2 (•-2)) generation, superoxide dismutase (SOD) activity and protein level, sirtuin 3 (SIR3) protein level, correlation between manganese (Mn) SOD and SIR, total antioxidant capacity, and malondialdehyde were measured following exposure of hFOB 1.19 cells to TiO2NPs. Exposure of hFOB 1.19 cells to TiO2NPs resulted in: (1) cellular uptake of NPs; (2) increased cytotoxicity and cell death in a time- and concentration-dependent manner; (3) ultrastructure changes; (4) decreased SOD and ALP activity; (5) decreased protein levels of SOD1, SOD2, and SIR3; (6) decreased total antioxidant capacity; (7) increased O2 (•-) generation; and (8) enhanced lipid peroxidation (malondialdehyde level). The linear relationship between the protein level of MnSOD and SIR3 and between O2 (•-) content and SIR3 protein level was observed. Importantly, the cytotoxic effects of TiO2NPs were attenuated by the pretreatment of hFOB 1.19 cells with SOD, indicating the significant role of O2 (•-) in the cell damage and death observed. Thus, decreased expression of SOD leading to increased oxidizing stress may underlie the nanotoxic effects of TiO2NPs on human osteoblasts.
... There is a great deal of evidence that supports the biological plausibility of the induced adverse health effects from exposure to ambient air pollutants. Epidemiological studies suggest that inflammation or oxidative stress is produced when oxidants, metals, or reactive organic compounds found in these pollutants generate reactive oxygen species or free radicals, which damage DNA, thus promoting disease (Barry, 1991;Li et al., 2003, Risom, Moller & Loft, 2005Bhattacharya, Alink, & Dopp, 2007;Rahman, Morrison, Donaldson, & MacNee, 1996). The development of free radicals and their effect on the body at the cellular level are associated with increased oxidative stress, which contributes to lung inflammation as seen in asthmatics (Rahman et al., 1996). ...
... A 260 /A 280 =1.82) [39,40]. Excessive generation of ROS overwhelms the antioxidant defense system that can oxidize DNA and generate a large number of oxidative DNA modifications, including strand breaks and base oxidations [41]. Increased DNA breakdown results an increased rate of cell death [8], which may explain the decreased DNA content in nicotine treated liver tissues. ...
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