scholarly journals DNA damage after long-term repetitive hyperbaric oxygen exposure

2009 ◽  
Vol 106 (1) ◽  
pp. 311-315 ◽  
Author(s):  
Michael Gröger ◽  
Sükrü Öter ◽  
Vladislava Simkova ◽  
Markus Bolten ◽  
Andreas Koch ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Endurance Training ◽  
Hyperbaric Oxygen ◽  
Oxidative Dna Damage ◽  
Ex Vivo ◽  
Pure Oxygen ◽  
Repetitive Exposure

A single exposure to hyperbaric oxygen (HBO), i.e., pure oxygen breathing at supra-atmospheric pressures, causes oxidative DNA damage in humans in vivo as well as in isolated lymphocytes of human volunteers. These DNA lesions, however, are rapidly repaired, and an adaptive protection is triggered against further oxidative stress caused by HBO exposure. Therefore, we tested the hypothesis that long-term repetitive exposure to HBO would modify the degree of DNA damage. Combat swimmers and underwater demolition team divers were investigated because their diving practice comprises repetitive long-term exposure to HBO over years. Nondiving volunteers with and without endurance training served as controls. In addition to the measurement of DNA damage in peripheral blood (comet assay), blood antioxidant enzyme activities, and the ratio of oxidized and reduced glutathione content, we assessed the DNA damage and superoxide anion radical (O2•−) production induced by a single ex vivo HBO exposure of isolated lymphocytes. All parameters of oxidative stress and antioxidative capacity in vivo were comparable in the four different groups. Exposure to HBO increased both the level of DNA damage and O2•− production in lymphocytes, and this response was significantly more pronounced in the cells obtained from the combat swimmers than in all the other groups. However, in all groups, DNA damage was completely removed within 1 h. We conclude that, at least in healthy volunteers with endurance training, long-term repetitive exposure to HBO does not modify the basal blood antioxidant capacity or the basal level of DNA strand breaks. The increased ex vivo HBO-related DNA damage in isolated lymphocytes from these subjects, however, may reflect enhanced susceptibility to oxidative DNA damage.

Abstract 424: Vascular Smooth Muscle Cell Expression of S100a12 in Vivo Induces Enhanced Oxidative Stress & Vascular Remodeling

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Marion Hofmann Bowman ◽  
Jeannine Wilk ◽  
Gene Kim ◽  
Yanmin Zhang ◽  
Jalees Rehman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Smooth Muscle ◽  
Vascular Remodeling ◽  
Oxidative Dna Damage ◽  
Fold Increase ◽  
Brdu Incorporation ◽  
Elastic Fibers ◽  
Nuclear Staining

S100A12 is a small calcium binding protein that is a signal transduction ligand of the receptor for advance glycation endproducts (RAGE). S100A12, like RAGE, is expressed in the vessel wall of atherosclerotic vasculature, particularly in smooth muscle cells (SMC). While RAGE has been extensively implicated in inflammatory states such as atherosclerosis, the role of S100A12 is less clear. We tested the hypothesis that expression of human S100A12 directly exacerbates vascular inflammation. Several lines of Bl6/J transgenic mice (tg) expressing human S100A12 in SMC under control of the SM22a promoter were generated. Primary aortic SMC from tg and wild type (wt) littermates were isolated and analyzed for (i) proliferation using MTS/Formazan Assay and BrdU incorporation, (ii) oxidative stress using using flow cytometry with MitoSOX antibody, oxidative DNA damage using immunofluorescence microscopy with anti-8-oxo-dG antibody, and NF-kB activation measured by EMSA and (iii) cytokine expression measured by IL-6 ELISA. Furthermore, the aortas from tg and wt mice were examined. Results: Tg but not wt SMC expressed S100A12 protein. Tg SMC had a significant 1.9 to 2.7 fold increase in conversion of MTS into Formazan at 24–96 hours likely reflective of increased metabolic activity since BrdU incorporation into DNA was less in tg compared to wt SMC (4% vs 21% positive BrdU nuclei, p <0.05). Tg SMC showed significantly higher levels of mitochondrial generated ROS, nuclear staining for oxidative DNA damage which was not detected in the nuclei of wt SMC’s, and a 2.5 fold increase in NFkB activity. IL-6 production at baseline was higher in tg SMC’s (615 vs 213 pg/ml, p< 0.05) and increased dramatically after LPS treatment (10 ng/ml) in tg SMC’s (2130 vs 415 pg/ml). Histologic examination of the thoracic aorta at 10 weeks of age revealed increased collagen deposition in the aortic media with fragmentation and disarray of elastic fibers. In vivo ultrasound revealed a progressive dilation of the aortic arch from age 10 weeks to 16 weeks of age (1.27 to 1.60 mm, p<0.05) in tg but not in wt littermate mice (1.30 to 1.33 mm, p=0.1). These data reveal the novel finding that targeted expression of human S100A12 in SMC modulates oxidative stress, inflammation and vascular remodeling.

scholarly journals Dual Roles of Helicobacter pylori NapA in Inducing and Combating Oxidative Stress

2006 ◽  
Vol 74 (12) ◽  
pp. 6839-6846 ◽  
Author(s):  
Ge Wang ◽  
Yang Hong ◽  
Adriana Olczak ◽  
Susan E. Maier ◽  
Robert J. Maier
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Wild Type Mouse ◽  
Wild Type ◽  
Oxygen Intermediates ◽  
Physiological Analysis ◽  
H Pylori

ABSTRACT Neutrophil-activating protein (NapA) has been well documented to play roles in human neutrophil recruitment and in stimulating host cell production of reactive oxygen intermediates (ROI). A separate role for NapA in combating oxidative stress within H. pylori was implied by studies of various H. pylori mutant strains. Here, physiological analysis of a napA strain was the approach used to assess the iron-sequestering and stress resistance roles of NapA, its role in preventing oxidative DNA damage, and its importance to mouse colonization. The napA strain was more sensitive to oxidative stress reagents and to oxygen, and it contained fourfold more intracellular free iron and more damaged DNA than the parent strain. Pure, iron-loaded NapA bound to DNA, but native NapA did not, presumably linking iron levels sensed by NapA to DNA damage protection. Despite its in vitro phenotype of sensitivity to oxidative stress, the napA strain showed normal (like that of the wild type) mouse colonization efficiency in the conventional in vivo assay. By use of a modified mouse inoculation protocol whereby nonviable H. pylori is first inoculated into mice, followed by (live) bacterial strain administration, an in vivo role for NapA in colonization efficiency could be demonstrated. NapA is the critical component responsible for inducing host-mediated ROI production, thus inhibiting colonization by the napA strain. An animal colonization experiment with a mixed-strain infection protocol further demonstrated that the napA strain has significantly decreased ability to survive when competing with the wild type. H. pylori NapA has unique and separate roles in gastric pathogenesis.

The Iron Chelator L1 Potentiates Oxidative DNA Damage in Iron-Loaded Liver Cells

Blood ◽  
1998 ◽  
Vol 92 (2) ◽  
pp. 632-638 ◽  
Author(s):  
Louise Cragg ◽  
Robert P. Hebbel ◽  
Wesley Miller ◽  
Alex Solovey ◽  
Scott Selby ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Dna Damage ◽  
Iron Overload ◽  
Oxidative Dna Damage ◽  
Iron Chelator ◽  
Liver Cells ◽  
Iron Chelators

Abstract Iron-mediated carcinogenesis is thought to occur through the generation of oxygen radicals. Iron chelators are used in attempts to prevent the long term consequences of iron overload. In particular, 1,2-dimethyl-3-hydroxypyrid-4-one (L1), has shown promise as an effective chelator. Using an established hepatocellular model of iron overload, we studied the generation of iron-catalyzed oxidative DNA damage and the influence of iron chelators, including L1, on such damage. Iron loading of HepG2 cells was found to greatly exacerbate hydrogen peroxide–mediated DNA damage. Desferrithiocin was protective against iron/hydrogen peroxide–induced DNA damage; deferoxamine had no effect. In contrast, L1 exposure markedly potentiated hydrogen peroxide–mediated oxidative DNA damage in iron-loaded liver cells. However, when exposure to L1 was maintained during incubation with hydrogen peroxide, L1 exerted a protective effect. We interpret this as indicating that L1's potential toxicity is highly dependent on the L1:iron ratio. In vitro studies examining iron-mediated ascorbate oxidation in the presence of L1 showed that an L1:iron ratio must be at least 3 to 1 for L1 to inhibit the generation of free radicals; at lower concentrations of L1 increased oxygen radical generation occurs. In the clinical setting, such potentiation of iron-catalyzed oxidative DNA damage at low L1:iron ratios may lead to long-term toxicities that might preclude administration of L1 as an iron chelator. Whether this implication in fact extends to the in vivo situation will have to be verified in animal studies.

Neonatal Benzo[a]pyrene Exposure Induces Oxidative Stress and DNA Damage Causing Neurobehavioural Changes during the Early Adolescence Period in Rats

2016 ◽  
Vol 38 (2) ◽  
pp. 150-162 ◽  
Author(s):  
Bhupesh Patel ◽  
Saroj Kumar Das ◽  
Manorama Patri
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Brain Development ◽  
Early Adolescence ◽  
Hippocampal Neurons ◽  
Oxidative Dna Damage ◽  
Specific Effect ◽  
Adolescence Period

Humans are exposed to polycyclic aromatic hydrocarbons (PAHs) by ingestion of contaminated food and water. Prenatal exposure to benzo[a]pyrene (B[a]P) like PAHs through the placental barrier and neonatal exposure by breast milk and the environment may affect early brain development. In the present study, single intracisternal administration of B[a]P (0.2 and 2.0 µg/kg body weight) to male Wistar rat pups at postnatal day 5 (PND5) was carried out to study its specific effect on neonatal brain development and its consequences at PND30. B[a]P administration showed a significant increase in exploratory and anxiolytic-like behaviour with elevated hippocampal lipid peroxidation and protein oxidation at PND30. Further, DNA damage was estimated in vitro (Neuro2a and C6 cell lines) by the comet assay, and oxidative DNA damage of hippocampal sections was measured in vivo following exposure to B[a]P. DNA strand breaks (single and double) significantly increased due to B[a]P at PND30 in hippocampal neurons and increased the nuclear tail moment in Neuro2a cells. Hippocampal 8-oxo-2′-deoxyguanosine production was significantly elevated showing expression of more TUNEL-positive cells in both doses of B[a]P. Histological studies also revealed a significant reduction in mean area and perimeter of hippocampal neurons in rats treated with B[a]P 2.0 μg/kg, when compared to naïve and control rats. B[a]P significantly increased anxiolytic-like behaviour and oxidative DNA damage in the hippocampus causing apoptosis that may lead to neurodegeneration in adolescence. The findings of the present study address the potential role of B[a]P in inducing oxidative stress-mediated neurodegeneration in the hippocampus through oxidative DNA damage in the early adolescence period of rats.

The Iron Chelator L1 Potentiates Oxidative DNA Damage in Iron-Loaded Liver Cells

Blood ◽  
1998 ◽  
Vol 92 (2) ◽  
pp. 632-638 ◽  
Author(s):  
Louise Cragg ◽  
Robert P. Hebbel ◽  
Wesley Miller ◽  
Alex Solovey ◽  
Scott Selby ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Dna Damage ◽  
Iron Overload ◽  
Oxidative Dna Damage ◽  
Iron Chelator ◽  
Liver Cells ◽  
Iron Chelators

Iron-mediated carcinogenesis is thought to occur through the generation of oxygen radicals. Iron chelators are used in attempts to prevent the long term consequences of iron overload. In particular, 1,2-dimethyl-3-hydroxypyrid-4-one (L1), has shown promise as an effective chelator. Using an established hepatocellular model of iron overload, we studied the generation of iron-catalyzed oxidative DNA damage and the influence of iron chelators, including L1, on such damage. Iron loading of HepG2 cells was found to greatly exacerbate hydrogen peroxide–mediated DNA damage. Desferrithiocin was protective against iron/hydrogen peroxide–induced DNA damage; deferoxamine had no effect. In contrast, L1 exposure markedly potentiated hydrogen peroxide–mediated oxidative DNA damage in iron-loaded liver cells. However, when exposure to L1 was maintained during incubation with hydrogen peroxide, L1 exerted a protective effect. We interpret this as indicating that L1's potential toxicity is highly dependent on the L1:iron ratio. In vitro studies examining iron-mediated ascorbate oxidation in the presence of L1 showed that an L1:iron ratio must be at least 3 to 1 for L1 to inhibit the generation of free radicals; at lower concentrations of L1 increased oxygen radical generation occurs. In the clinical setting, such potentiation of iron-catalyzed oxidative DNA damage at low L1:iron ratios may lead to long-term toxicities that might preclude administration of L1 as an iron chelator. Whether this implication in fact extends to the in vivo situation will have to be verified in animal studies.

Serum of 8-OHdG as a potential biomarker of oxidative DNA damage in workers exposed to harmful working environments

2020 ◽  
pp. 783-783
Author(s):  
I. A. Umnyagina ◽  
L. A. Strakhova ◽  
T. V. Blinova
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Blood Serum ◽  
Oxidative Dna Damage ◽  
Working Environment ◽  
Working Environments ◽  
Potential Biomarker ◽  
High Level ◽  
Damage Marker

In the blood serum of 70% individuals exposed to harmful factors of the working environment, a high level of oxidative stress and the DNA damage marker 8-Hydroxy-2’-Deoxyguanosine (8-OHdG) were detected.

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