Mechanism Of Oxidative Damage Research Articles

Mechanisms of oxidative DNA damage induced by carcinogenic arylamines

Most arylamines are pro-carcinogens, and require metabolic activation to yield ultimate carcinogen metabolites. O-Acetylation of the N-hydroxy form of an arylamine yields an acetoxyarylamine, which can form a highly reactive arylnitrenium ion, the ultimate metabolite responsible for DNA adduct formation. However, we demonstrate here that the N-hydroxy and nitroso forms of arylamines can also induce DNA damage, including 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodG) lesions, via reactive oxygen species formation. The N-hydroxy and nitroso derivatives of carcinogenic arylamines may contribute to the carcinogenic process through H2O2 formation. N-Hydroxy derivatives induce metal-mediated DNA damage, with remarkable enhancement by NADH. Nitroso derivatives induce NADH-dependent DNA damage in the presence of metal ions. Hydroxy derivatives of arylamines formed by enzymatic hydroxylation or as o- or p-aminophenols can also induce DNA damage in the presence of metal ions. The autoxidation of o-phenylenediamine and several arylamine metabolites is accelerated in the presence of SOD or manganese, resulting in the enhancement of metal-mediated DNA damage. The oxidative DNA damage induced by arylamine compounds may participate in chemical carcinogenesis, in addition to DNA adduct formation.

Mechanisms of oxidative damage in multiple sclerosis and a cell therapy approach to treatment.

Although significant advances have recently been made in the understanding and treatment of multiple sclerosis, reduction of long-term disability remains a key goal. Evidence suggests that inflammation and oxidative stress within the central nervous system are major causes of ongoing tissue damage in the disease. Invading inflammatory cells, as well as resident central nervous system cells, release a number of reactive oxygen and nitrogen species which cause demyelination and axonal destruction, the pathological hallmarks of multiple sclerosis. Reduction in oxidative damage is an important therapeutic strategy to slow or halt disease processes. Many drugs in clinical practice or currently in trial target this mechanism. Cell-based therapies offer an alternative source of antioxidant capability. Classically thought of as being important for myelin or cell replacement in multiple sclerosis, stem cells may, however, have a more important role as providers of supporting factors or direct attenuators of the disease. In this paper we focus on the antioxidant properties of mesenchymal stem cells and discuss their potential importance as a cell-based therapy for multiple sclerosis.

Mechanistic Insight into DNA Damage and Repair in Ischemic Stroke: Exploiting the Base Excision Repair Pathway as a Model of Neuroprotection

Stroke is a common cause of death and serious long-term adult disability. Oxidative DNA damage is a severe consequence of oxidative stress associated with ischemic stroke. The accumulation of DNA lesions, including oxidative base modifications and strand breaks, triggers cell death in neurons and other vulnerable cell populations in the ischemic brain. DNA repair systems, particularly base excision repair, are endogenous defense mechanisms that combat oxidative DNA damage. The capacity for DNA repair may affect the susceptibility of neurons to ischemic stress and influence the pathological outcome of stroke. This article reviews the accumulated understanding of molecular pathways by which oxidative DNA damage is triggered and repaired in ischemic cells, and the potential impact of these pathways on ischemic neuronal cell death/survival. Genetic or pharmacological strategies that target the signaling molecules in DNA repair responses are promising for potential clinically effective treatment. Further understanding of mechanisms for oxidative DNA damage and its repair processes may lead to new avenues for stroke management.

Inhibitors of Catalase-Amyloid Interactions Protect Cells from β-Amyloid-Induced Oxidative Stress and Toxicity

Compelling evidence shows a strong correlation between accumulation of neurotoxic β-amyloid (Aβ) peptides and oxidative stress in the brains of patients afflicted with Alzheimer disease (AD). One hypothesis for this correlation involves the direct and harmful interaction of aggregated Aβ peptides with enzymes responsible for maintaining normal, cellular levels of reactive oxygen species (ROS). Identification of specific, destructive interactions of Aβ peptides with cellular anti-oxidant enzymes would represent an important step toward understanding the pathogenicity of Aβ peptides in AD. This report demonstrates that exposure of human neuroblastoma cells to cytotoxic preparations of aggregated Aβ peptides results in significant intracellular co-localization of Aβ with catalase, an anti-oxidant enzyme responsible for catalyzing the degradation of the ROS intermediate hydrogen peroxide (H(2)O(2)). These catalase-Aβ interactions deactivate catalase, resulting in increased cellular levels of H(2)O(2). Furthermore, small molecule inhibitors of catalase-amyloid interactions protect the hydrogen peroxide-degrading activity of catalase in Aβ-rich environments, leading to reduction of the co-localization of catalase and Aβ in cells, inhibition of Aβ-induced increases in cellular levels of H(2)O(2), and reduction of the toxicity of Aβ peptides. These studies, thus, provide evidence for the important role of intracellular catalase-amyloid interactions in Aβ-induced oxidative stress and propose a novel molecular strategy to inhibit such harmful interactions in AD.

Tempol attenuates cocaine-induced death of PC12 cells through decreased oxidative damage

The association between cocaine administration and induction of oxidative stress in different brain regions suggests that oxidative damage is an important factor participating in cocaine disruption of normal central nervous system functions. In order to deal with this topic, brain penetrating exogenous antioxidants were suggested as a tool to prevent cocaine-induced oxidative damage and behavioral changes. Lately, we have shown that Tempol, a stable nitroxide radical reduced oxidative damage and attenuated the development and expression of cocaine psychomotor sensitization. To examine whether nitroxides, represented by Tempol, can exhibit protective effects against cocaine-induced cell death and to elucidate the molecular mechanism of cocaine-induced oxidative damage, we used the well established PC12 cell line model. The results showed that (1) cocaine induced cell death in a dose-dependent manner (2) and that it was reduced significantly by the stable nitroxide radical Tempol. Furthermore, (3) Tempol significantly inhibited oxidative damage induced by cocaine as reflected by mitochondrial superoxide radical and peroxide enhancement. Finally, (4) Tempol restored the total scavenging capacity which was reduced by cocaine in PC12 cells. Cumulatively, these results suggest that nitroxides such as Tempol can attenuate oxidative damage and cell death induced by cocaine and that PC12 cells can be used as an in vitro model to further investigate the precise molecular mechanism of these compounds.

The mechanism of oxidative damage in the nephrotoxicity of mice caused by nano-anatase TiO2

While the nephrotoxicity of high-dose nano-TiO2 has been demonstrated, very little is known about the mechanism of oxidative stress to the animal kidney. In order to understand the nephrotoxicity of nano-anatase TiO2 particles, various biochemical and chemical parameters were assayed in mouse kidneys. Abdominal exposures of high-dose nano-anatase TiO2 caused nephritis and oxidative stress to kidney. An increase in coefficients of the kidney, Ti accumulation and histopathological changes in kidney could be observed, followed by increased reactive oxygen species generation and lipid peroxidation, and decreased activities of superoxide dismutase, catalase, ascorbate peroxidase and total antioxidant capacity as well as antioxidants such as glutathione and ascorbic acid content. In addition, kidney functions were disrupted, including increase of the creatinine, calcium and phosphonium, and reduction of uric acid and blood urea nitrogen. Our results suggest that nephritis generation in mice caused by nano-anatase TiO2 particles is closely related to oxidative stress.

Anaerobic storage of red blood cells.

Anaerobic storage of red blood cells.

COMPARATIVE IN VITRO EFFECTS OF SOME METAL IONS ON BOVINE KIDNEY CORTEX GLUTATHIONE REDUCTASE

Heavy metal pollution can arise from many sources and damage many organisms. Exposure to the metal ions can leads to a reduction in cellular antioxidant enzyme activities and lowers cellular defense against oxidative stress. In this study we have tested effects of the some metal ions on the purified bovine kidney cortex glutathione reductase (GR). Cadmium (Cd2+), nickel (Ni2+), and zinc (Zn2+) showed inhibitory effect on the enzyme. The obtained IC50 values of Cd2+, Ni2+, and Zn2+ are 0.027, 0.8, and 1 mM, respectively. Kinetic characterization of the inhibition is also investigated. Cd2+ inhibition is noncompetitive with respect to both oxidized glutathione (GSSG) (KiGSSG 0.060 ± 0.005 mM) and NADPH (KiNADPH 0.025 ± 0.002 mM). Ni2+ inhibition is noncompetitive with respect to GSSG (KiGSSG 0.329 ± 0.016 mM) and uncompetitive with respect to NADPH (KiNADPH 0.712 ± 0.047 mM). The effect of Zn2+ on GR activity is consistent with noncompetitive inhibition pattern when the varied substrate is the GSSG (KiGSSG 0.091 ± 0.005 mM) and the NADPH (KiNADPH 0.226 ± 0.01 mM), respectively. GR inhibition studies may be useful for understanding the mechanisms for oxidative damage associated with heavy metal toxicity.

Mitochondrial decay is involved in BaP-induced cervical damage

Benzo[ a]pyrene (BaP) is a polycyclic aromatic hydrocarbon and a potent inducer of carcinogenesis. Many studies have reported that the carcinogenic effects of BaP might be due to its intermediate metabolites and to reactive oxygen species (ROS) that cause oxidative damage to the cells. However, the mechanisms of BaP-induced oxidative damage in cervical tissue are still not clear. We studied these mechanisms in female ICR mice treated with BaP either orally or intraperitoneally by measuring (1) several general biomarkers of oxidative stress in serum, (2) mitochondrial function in the cervix, and (3) the morphology of mitochondria in cervical tissue. BaP treatment (1) significantly lowered levels of vitamins A, C, and E and of glutathione; (2) reduced activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferases; and (3) significantly increased lipid peroxidation levels. In addition, significant increases in the levels of superoxide anion, hydrogen peroxide, and hydroxyl radical were observed. These results were confirmed by morphological changes in mitochondria and by decreases in membrane potential levels and in succinate dehydrogenase and malate dehydrogenase activities. The changes in these biomarkers and mitochondrial damage were BaP-dose-dependent and eventually induced both cell apoptosis and necrosis in cervical tissue. As mitochondria are the major sites of ROS generation, these findings show that mitochondrial decay greatly contributes to BaP-induced cervical damage.

Theoretical Investigations on the Thermal Decomposition Mechanism of 5-Hydroxy-6-hydroperoxy-5,6-dihydrothymidine in Water

The main primary product of DNA oxidation by free radicals is 5-hydroxy-6- hydroperoxy-5,6-dihydrothymidine (5-OH-6-OOH-DHT), whose further degradation can yield the other mutagenic products and amplify the spectrum of DNA damage. In this study, to illustrate the thermal stability of 5-OH-6-OOH-DHT in DNA, the decomposition mechanism of 5-OH-6-OOH-DHT was identified based on the cis-(5R,6S) diastereomer. Optimized structures for all of the stationary points in the gas phase were investigated at the B3LYP/6-31+G(d,p) level of theory. Four pathways were characterized. The decomposition mechanism of 5-OH-6-OOH-DHT was proposed to involve either dehydration for paths A and B or the cleavage of a glycosidic bond for paths C and D. Moreover, to simulate the title reaction in aqueous solution, a water-mediated mechanism and cluster-continuum model, based on the SCRF/CPCM model, were taken into account. The results indicate that the most favorable reaction pathways for paths A and B both involve a sort of eight-membered ring transition structure formed by two (path A) or one (path B) auxiliary water molecules, suggesting that the thermal decomposition of 5-OH-6-OOH-DHT can be significantly facilitated by water molecules. Path A is the most feasible mechanism reported for the decomposition of 5-OH-6-OOH-DHT in the aqueous solution, which is slightly more favorable than path B. However, the unimolecular decomposition mechanisms (paths C and D) both have high-energy barriers and are largely endothermic, suggesting that the cleavage of the N-glycosidic bond via unimolecular decomposition is thermodynamically and kinetically unfavorable. These studies have shed light on the chemical properties of 5-OH-6-OOH-DHT in free radical reactions and thereby have provided new insights into the complex mechanism of oxidative DNA damage.

Assessment of oxidative DNA damage and repair at single cellular level via real-time monitoring of 8-OHdG biomarker

8-Hydroxydeoxyguanosine (8-OHdG) is the most important and best-documented biomarker of oxidative stress, which is involved in the instigation of various diseases. 8-OHdG levels correlate to oxidative DNA damage which is known to be the root cause of a variety of age-related chronic diseases. The purpose of our research was to develop a detection strategy capable of measuring 8-OHdG in real-time at the surface of a single cell. Activated carbon fiber microelectrodes were used as the sensing platform. The microelectrodes were used to measure 8-OHdG release from single lung epithelial cells under the influence of nicotine. In order to evaluate the direct role of nicotine in tobacco induced genotoxicity, we studied the influence of parameters such as nicotine concentration and exposure times on 8-OHdG secretion. 2–8 mM nicotine solutions induced dose-dependent DNA damage in single cells, which was observed via amperometric measurements of secreted 8-OHdG biomarker. Real-time 8-OHdG measurements from single cells exposed to 4 mM nicotine solution revealed cessation of 8-OHdG secretion after 110 min. We have successfully outlined a methodology to detect 8-OHdG at the surface of single cells. A similar protocol can be used to evaluate oxidative DNA damage and repair mechanisms in other disease models.

Acetyl- l-carnitine protects neuronal function from alcohol-induced oxidative damage in the brain

The studies presented here demonstrate the protective effect of acetyl- l-carnitine (ALC) against alcohol-induced oxidative neuroinflammation, neuronal degeneration, and impaired neurotransmission. Our findings reveal the cellular and biochemical mechanisms of alcohol-induced oxidative damage in various types of brain cells. Chronic ethanol administration to mice caused an increase in inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine adduct formation in frontal cortical neurons but not in astrocytes from brains of these animals. Interestingly, alcohol administration caused a rather selective activation of NADPH oxidase (NOX), which, in turn, enhanced levels of reactive oxygen species (ROS) and 4-hydroxynonenal, but these were predominantly localized in astrocytes and microglia. Oxidative damage in glial cells was accompanied by their pronounced activation (astrogliosis) and coincident neuronal loss, suggesting that inflammation in glial cells caused neuronal degeneration. Immunohistochemistry studies indicated that alcohol consumption induced different oxidative mediators in different brain cell types. Thus, nitric oxide was mostly detected in iNOS-expressing neurons, whereas ROS were predominantly generated in NOX-expressing glial cells after alcohol ingestion. Assessment of neuronal activity in ex vivo frontal cortical brain tissue slices from ethanol-fed mice showed a reduction in long-term potentiation synaptic transmission compared with slices from controls. Coadministration of ALC with alcohol showed a significant reduction in oxidative damage and neuronal loss and a restoration of synaptic neurotransmission in this brain region, suggesting that ALC protects brain cells from ethanol-induced oxidative injury. These findings suggest the potential clinical utility of ALC as a neuroprotective agent that prevents alcohol-induced brain damage and development of neurological disorders.

Study on Hepatotoxicity on rats caused by crude extracts of totalsaikosaponins `and correlation with oxidative damage mechanism

To observe the degree of hepatotoxicity damage to rats and the correlation with oxidative damage mechanism after taking a large dose of crude extracts of total saikosaponins for a long time. According to 45-day toxicity experimental methods, rats were successively administrated with crude extracts of total saikosaponins. High, middle and low dose were respectively 100, 50, 10 mg x kg(-1) calculated by total saikosaponins. The general conditions were observed and the related index of liver function, the metabolism condition of lipids, the glycometabolism, the level of TBIL were determined and the histopathologic examination of hepatic tissue were examined. The content of total-SH in serum, the level of MDA, the activity of SOD and the content and activity of GSH and GSH-Px in serum and liver tissue were detected. The crude extracts of total saikosaponins can increase the activity of ALT and AST in blood, increase liver weight and the ratio of liver to body, increase the content of TG in blood and liver. The effect on CHO in blood and Gn in liver is not obvious. Only high dose group's effect on TBIL can be observed. The hepatic cell damage is obvious in the histopathologic examination of hepatic tissue. The crude extracts of total saikosaponins can increase the content of total SH in blood, the content of MDA and GSH in blood and liver, while decrease the activity of SOD and GSH-Px in blood and liver. The above-mentioned changes gradually aggravates with dose increasing, and is obvious compared with distilled water control group. The crude extracts of total saikosaponinscan induce hepatotoxicity damage, and the mechanism of hepatic damage is related with oxidative damage mechanism.

Green tea: protective action against oxidative damage induced by xenobiotics

The indiscriminate usage of synthetic chemicals and pesticides has led to a widespread contamination of land, water and air with harmful xenobiotics. The exposure to these toxicants results in severe health effects on organisms. Also, some natural foods contain harmless chemical species (nitrate), which however become toxic on certain conditions. Hence it is pertinent to focus attention on commonly consumed plant food materials, which can neutralize the toxicity damage caused by environmental agents. One of the most important sources of antioxidants is green tea. This review focuses on the mechanisms of oxidative damage caused by different xenobiotics and the defensive action of green tea in mitigating the damage. It is concluded that tea polyphenols, catechins and flavonoids scavenge reactive oxygen species and render a protective effect.

Rat liver mitochondria impairments under acute carbon tetrachloride-induced intoxication. Effects of melatonin

The aim of the present work was to investigate the mechanisms of oxidative damage of rat liver mitochondria in vitro, under hypochlorous acid (HOCl)-induced oxidative stress, and in vivo, under acute carbon tetrachloride-induced intoxication in rats. Hypochlorous acid (50–300 μM), the main inflammatory agent, inhibited liver mitochondria respiratory activity and caused uncoupling in the respiratory and phos-porylation processes. The toxic damage of rat liver after 24 h of acute carbon tetrachloride-induced intoxication (4 g/kg, intragastrically) was accompanied by a significant reduction in succinate- and glutamate-dependent respiration rate in state 3 (by 65%, p < 0.001, and by 50%, p < 0.01, respectively). The respiration control ratio approached 1, reflecting the loss of respiration control. The phosphorylation coefficient significantly decreased due to uncoupling of the oxidation and phosphorylation processes. The mitochondrial alterations were associated with oxidation of intramitochondrial GSH by 25% (p < 0.05), the marked inhibition of succinate dehydrogenase (complex II) by 35% (p < 0.05), and the rise of blood plasma nitric oxide level by 45% (p < 0.05). The impairment of mitochondrial respiratory function may result from the inhibition of enzymatic activities in the respiratory chain and the damage of mitochondrial membrane during intoxication and plays a key role in the development of the CCl4-induced hepatotoxicity. Melatonin administration under CCl4-induced intoxication (three times at a dose of 10 mg/kg) increased the rate of succinate oxidation in state 3 by 30% (p < 0.05) and reversed the increase in glutathione peroxidase activity. Melatonin prevented an elevation of nitric oxide level in the blood plasma of intoxicated animals but did not protect mitochondrial functions under acute intoxication.

Oxidative stress and expression of heme oxygenase-1 mRNA in the myocardial tissue of rats after limb ischemia/ reperfusion injury

Objective To study the mechanism of oxidative damage in myocardial tissue after limb ischemia reperfusion (IR), and the protective effects of heme oxygenase-1 on myocardial injury in experimental rats. Method The models of bilateral hind limbs ischemia and reperfusion in rats were established by using tourniquets applied to the roots of both hind limbs until palm blanched and pulseless for 4 hours. A total of 56 SD rats were randomly (random number) divided into 7 groups, namely one normal control group ( n = 8) and 6 ischemia-reperfusion groups as per different lengths of reperfusion time, e. g. 2 hrs, 4 hrs, 8 hrs, 16 h rs and 24 hr ( n = 8 each). The experimental rats were sacrificed after different lengths of reperfusion time. Specimens of myocardium and blood were taken for assays of malonaldehyde (MDA), superoxide dismutase (SOD) and myeloperoxidase (MPO), and pathological changes of myocardium were observed, and the expressions of HO-1 mRNA in myocardium were detected. Data were analyzed with ANOVA. Results (1) Compared with the control group, the levels of serum MDA and myocardial MDA of rats were increased in all IR groups and were higher (P 0.05), and after reperfusion for 4 hours and over, the expressions of HO-1 mRNA were markedly increased in IR groups and reached peak after reperfusion for 16 hours in comparison with the control group (P < 0.05). Conclusions The activation of neutrophils and free radicals may play a primarily adverse role in myocardial injury after limb IR, and the increase in the expression of HO-1 mRNA lessens the harm effects of IR on myocardium. Key words: Ischemia/reperfusion; Heme oxygenase-1; Oxidative stress; Myocardium; Limb; Malonaldehyde (MDA); Myeloperoxidase( MPO); Superoxide dismutase(SOD)

Oxidative damage increases intracellular free calcium [Ca 2+] i concentration in human erythrocytes incubated with lead

One important effect of lead toxicity in erythrocytes consists of increasing [Ca 2+] i which in turn may cause alterations in cell shape and volume and it is associated with cellular rigidity, hemolysis, senescence and apoptosis. In this work, we proposed the use of erythrocytes incubated with Pb 2+ to assess association of the mechanisms of lead erythrocyte oxidative damage and calcium homeostasis. Lead incubation produced an increase in [Ca 2+] i dose- and time-dependent, which mainly involved Ca 2+ entry mechanism. Additionally, in this in vitro model alterations similar to erythrocytes of lead-exposed workers were produced: Increase in Ca 2+ influx, decrease in (Ca 2+–Mg 2+)-ATPase activity and GSH/GSGG ratio; increase in lipoperoxidation, protein carbonylation and osmotic fragility accompanied of dramatic morphological changes. Co-incubation with trolox, a soluble vitamin-E analog is able to prevent these alterations indicating that lead damage mechanism is strongly associated with oxidative damage with an intermediate toxic effect via [Ca 2+] i increase. Furthermore, erythrocytes oxidation induced with a free radical generator (APPH) showed effects in [Ca 2+] i and oxidative damage similar to those found in erythrocytes incubated with lead. Co-incubation with trolox prevents the oxidative effects induced by AAPH in erythrocytes. These results suggest that increase of [Ca 2+] i depends on the oxidative status of the erythrocytes incubated with lead. We consider that this model contributes in the understanding of the relation between oxidative damage induced by lead exposure and Ca 2+ homeostasis, the consequences related to these phenomena and the molecular basis of lead toxicity in no excitable cells.

Age‐Dependent Accumulation of Mitochondrial DNA Damage in Brain Tissues Derived from Apex1+/− Mice.

An age‐dependent accumulation of mutations in both somatic and germ cell tissues has been reported in many organisms. DNA damage induced by oxidative stress has been linked to increases in mutation frequencies. It has been shown that the activity of base excision repair (BER), the main repair mechanism for oxidative DNA damage, declines during aging in mouse brain tissue. The BER enzyme APEX1, may be limiting the repair capacity in aged mice. We sought to test the hypothesis that mtDNA damage increases in an age‐dependent fashion in brain tissues obtained from a BER‐deficient mouse model (Apex1+/−). We measured mtDNA damage by QPCR in 6, 16, and 28‐month‐old wild‐type (WT) and Apex1+/− mice. Our results show that the frequency of mtDNA lesions in the striatum from 16‐ and 28‐ month old Apex+/−mice are 0.42 lesions/10kb/strand and 0.53 lesions/10kb/strand, respectively. Cerebral cortex of 28‐month‐old WTandApex1 +/−mice exhibited a significant increased in lesion number as shown by lesion frequencies of 0.30 lesions/10kb/strand and 0.74 lesions/10kb/strand, respectively. In conclusion, our results show that deficient BER leads to an age‐dependent increase in mtDNA lesions in brain tissues and suggest an important role for BER in mtDNA stability. Supported by R25‐GM061838 and U54‐NS039408.

Rapid and sensitive electrochemical sensing of DNA damage induced by V 2O 5 nanobelts/HCl/H 2O 2 system in natural dsDNA layer-by-layer films

The detection of DNA damage is one of the most important topics in the DNA research fields. In the present work, oppositely charged natural dsDNA and poly(diallyldimethyl ammonium chloride) (PDDA) were assembled into (PDDA/dsDNA) 3 layer-by-layer films on electrode surface, and Ru(bpy) 3 2+ and Co(phen) 3 3+ in solution were used as electroactive probes to detect oxidative damage of natural dsDNA in the films after incubation of the films in V 2O 5 nanobelts/HCl/H 2O 2 solution. The mechanism of DNA oxidative damage caused by the V 2O 5 nanobelts/HCl/H 2O 2 system was similar to that of Fenton-type reaction. The reaction of V 2O 5 nanobelts with HCl would produce V(IV), and the produced V(IV) would further react with H 2O 2, generating hydroxyl radicals (OH ) as in the Fenton-type reaction, which could severely damage DNA in the films. The present work provided an in vitro model system to mimic the pathway of DNA damage in real bioprocess through a simple electrochemical approach combined with layer-by-layer assembly. This approach also showed promising applications in rapid and sensitive screening of new nanomaterials and chemicals in vitro for their potential genotoxicity.

Oxidative damage to RNA: mechanisms, consequences, and diseases

Overproduction of free radicals can damage cellular components resulting in progressive physiological dysfunction, which has been implicated in many human diseases. Oxidative damage to RNA received little attention until the past decade. Recent studies indicate that RNA, such as messenger RNA and ribosomal RNA, is very vulnerable to oxidative damage. RNA oxidation is not a consequence of dying cells but an early event involved in pathogenesis. Oxidative modification to RNA results in disturbance of the translational process and impairment of protein synthesis, which can cause cell deterioration or even cell death. In this review, we discuss the mechanisms of oxidative damage to RNA and the possible biological consequences of damaged RNA. Furthermore, we review recent evidence suggesting that oxidative damage to RNA may contribute to progression of many human diseases.