Dataset Information

Effects of ambient PM2.5 and 9-nitroanthracene on DNA damage and repair, oxidative stress and metabolic enzymes in the lungs of rats.

ABSTRACT: Ambient fine particulate matter (PM2.5) is a complex mixture associated with lung cancer risk. PM2.5-bound nitro-polycyclic aromatic hydrocarbons (NPAHs) have been demonstrated to possess mutagenicity and carcinogenicity. Previous studies showed that PM2.5 induced DNA damage, whereas there is little knowledge of whether 9-nitroanthracene (9-NA), a typical compound of NPAHs in PM2.5, causes DNA damage. Also, the regulating mechanisms of PM2.5 and 9-NA in DNA damage and repair are not yet fully established. Here we sought to investigate the molecular mechanisms of DNA damage and repair in the lungs of male Wistar rats exposed to PM2.5 (1.5 mg per kg body weight) or three different dosages of 9-NA. And then DNA strand breaks, 8-OH-dG formation, DNA-protein crosslink and DNA repair gene expressions in rat lungs were analyzed. In addition, alteration in oxidative stress factors and metabolic enzymes were detected. The results showed that (1) PM2.5 and higher dosage 9-NA (4.0 × 10-5 and 1.2 × 10-4 mg per kg body weight) significantly caused lung DNA damage, accompanied by increasing OGG1 expression while inhibiting MTH1 and XRCC1 expression, elevating the levels of GADD153, hemeoxygenase-1 and malondialdehyde, and promoting the activities of CYP450 isozymes and glutathione S-transferase. (2) 1.3 × 10-5 mg kg-1 9-NA exposure couldn't cause DNA damage and oxidative stress. (3) At the approximately equivalent dose level, PM2.5-induced DNA damage effects were more obvious than 9-NA with positive correlation. It suggests that DNA damage caused by PM2.5 and 9-NA may be mediated partially through influencing the DNA repair capacity and enhancing oxidative stress and biotransformation, and this negative effect of 9-NA might be related to the PM2.5-induced lung genotoxicity.

SUBMITTER: Li R

PROVIDER: S-EPMC6061955 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Effects of ambient PM2.5 and 9-nitroanthracene on DNA damage and repair, oxidative stress and metabolic enzymes in the lungs of rats.

Li Ruijin R Zhao Lifang L Zhang Li L Chen Minghui M Shi Jing J Dong Chuan C Cai Zongwei Z

Toxicology research 20170518 5

Ambient fine particulate matter (PM2.5) is a complex mixture associated with lung cancer risk. PM2.5-bound nitro-polycyclic aromatic hydrocarbons (NPAHs) have been demonstrated to possess mutagenicity and carcinogenicity. Previous studies showed that PM2.5 induced DNA damage, whereas there is little knowledge of whether 9-nitroanthracene (9-NA), a typical compound of NPAHs in PM2.5, causes DNA damage. Also, the regulating mechanisms of PM2.5 ...[more]

PMID: 30090532

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Project description:Particulate matter exposure is associated with respiratory and cardiovascular system dysfunction. Recently, we demonstrated that fine particles, also named PM2.5, modify the expression of some components of the angiotensin and bradykinin systems, which are involved in lung, cardiac and renal regulation. The endocrine kidney function is associated with the regulation of angiotensin and bradykinin, and it can suffer damage even as a consequence of minor alterations of these systems. We hypothesized that exposure to PM2.5 can contribute to early kidney damage as a consequence of an angiotensin/bradykinin system imbalance, oxidative stress and/or inflammation.After acute and subchronic exposure to PM2.5, lung damage was confirmed by increased bronchoalveolar lavage fluid (BALF) differential cell counts and a decrease of surfactant protein-A levels. We observed a statistically significant increment in median blood pressure, urine volume and water consumption after PM2.5 exposure. Moreover, increases in the levels of early kidney damage markers were observed after subchronic PM2.5 exposure: the most sensitive markers, ?-2-microglobulin and cystatin-C, increased during the first, second, sixth and eighth weeks of exposure. In addition, a reduction in the levels of specific cytokines (IL-1?, IL-6, TNF-?, IL-4, IL-10, INF-?, IL-17a, MIP-2 and RANTES), and up-regulated angiotensin and bradykinin system markers and indicators of a depleted antioxidant response, were also observed. All of these effects are in concurrence with the presence of renal histological lesions and an early pro-fibrotic state.Subchronic exposure to PM2.5 induced an early kidney damage response that involved the angiotensin/bradykinin systems as well as antioxidant and immune imbalance. Our study demonstrates that PM2.5 can induce a systemic imbalance that not only affects the cardiovascular system, but also affects the kidney, which may also overall contribute to PM-related diseases.

Project description:The main objective of this study was chemical characterization and source apportionment of the oxidative potential of ambient PM2.5 samples collected in an urban background area in Athens, Greece. Ambient PM2.5 samples were collected during the summer (June-September) of 2017 and winter (February-March) of 2018 at a residential, urban background site in the outlying neighborhood of the Demokritos National Laboratory in Athens, Greece. The collected PM samples were analyzed for their chemical constituents including metals and trace elements, water-soluble organic carbon (WSOC), elemental and organic carbon (EC/OC), and marker of biomass burning (i.e., levoglucosan). In addition, the DCFH in vitro assay was performed to determine the oxidative potential of the PM2.5 samples. We performed a series of statistical analyses, including Spearman rank-order correlation analysis, principal component analysis (PCA), and multi linear regression (MLR) to determine the most significant species (as source tracers) contributing to the oxidative potential of PM2.5. Our findings revealed that the intrinsic (per PM mass) and extrinsic (per m3 of air volume) oxidative potentials of the collected ambient PM2.5 samples were significantly higher than those measured in many urban areas around the world. The results of the MLR analyses indicated that the major pollution sources contributing to the oxidative potential of ambient PM2.5 were vehicular emissions (characterized by EC) (44%), followed by secondary organic aerosol (SOA) formation (characterized by WSOC) (16%), and biomass burning (characterized by levoglucosan) (9%). The oxidative potential of the collected ambient PM2.5 samples was also higher in summer compared to the winter, mainly due to higher concentrations of EC and WSOC during this season. Results from this study corroborate the impact of traffic and SOA on the oxidative potential of ambient PM2.5 in greater Athens area, and can be helpful in adopting appropriate public health policies regarding detrimental outcomes of exposure to PM2.5.

Project description:BackgroundDiabetes mellitus type 2 (T2DM) is associated with oxidative stress which in turn can lead to DNA damage. The aim of the present study was to analyze oxidative stress, DNA damage and DNA repair in regard to hyperglycemic state and diabetes duration.MethodsFemale T2DM patients (n = 146) were enrolled in the MIKRODIAB study and allocated in two groups regarding their glycated hemoglobin (HbA1c) level (HbA1c≤7.5%, n = 74; HbA1c>7.5%, n = 72). In addition, tertiles according to diabetes duration (DD) were created (DDI = 6.94±3.1 y, n = 49; DDII = 13.35±1.1 y, n = 48; DDIII = 22.90±7.3 y, n = 49). Oxidative stress parameters, including ferric reducing ability potential, malondialdehyde, oxidized and reduced glutathione, reduced thiols, oxidized LDL and F2-Isoprostane as well as the activity of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase were measured. Damage to DNA was analyzed in peripheral blood mononuclear cells and whole blood with single cell gel electrophoresis. DNA base excision repair capacity was tested with the modified comet repair assay. Additionally, mRNA expressions of nine genes related to base excision repair were analyzed in a subset of 46 matched individuals.ResultsNo significant differences in oxidative stress parameters, antioxidant enzyme activities, damage to DNA and base excision repair capacity, neither between a HbA1c cut off />7.5%, nor between diabetes duration was found. A significant up-regulation in mRNA expression was found for APEX1, LIG3 and XRCC1 in patients with >7.5% HbA1c. Additionally, we observed higher total cholesterol, LDL-cholesterol, LDL/HDL-cholesterol, triglycerides, Framingham risk score, systolic blood pressure, BMI and lower HDL-cholesterol in the hyperglycemic group.ConclusionBMI, blood pressure and blood lipid status were worse in hyperglycemic individuals. However, no major disparities regarding oxidative stress, damage to DNA and DNA repair were present which might be due to good medical treatment with regular health checks in T2DM patients in Austria.

Dataset Information

Effects of ambient PM2.5 and 9-nitroanthracene on DNA damage and repair, oxidative stress and metabolic enzymes in the lungs of rats.

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Effects of ambient PM<sub>2.5</sub> and 9-nitroanthracene on DNA damage and repair, oxidative stress and metabolic enzymes in the lungs of rats.

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