Oxidative DNA damage and oxidative stress in lead-exposed workers

2016 ◽  
Vol 36 (7) ◽  
pp. 744-754 ◽  
Author(s):  
M Dobrakowski ◽  
N Pawlas ◽  
A Kasperczyk ◽  
A Kozłowska ◽  
E Olewińska ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Oxidative Damage ◽  
Oxidative Dna Damage ◽  
Blood Lead ◽  
Antioxidant Defense System ◽  
Control Group ◽  
High Exposure ◽  
Human Leukocytes ◽  
Low Exposure

There are many discrepancies among the results of studies on the genotoxicity of lead. The aim of the study was to explore lead-induced DNA damage, including oxidative damage, in relation to oxidative stress intensity parameters and the antioxidant defense system in human leukocytes. The study population consisted of 100 male workers exposed to lead. According to the blood lead (PbB) levels, they were divided into the following three subgroups: a group with PbB of 20–35 μg/dL (low exposure to lead (LE) group), a group with a PbB of 35–50 µg/dL (medium exposure to lead (ME) group), and a group with a PbB of >50 μg/dL (high exposure to lead (HE) group). The control group consisted of 42 healthy males environmentally exposed to lead (PbB < 10 μg/dL). A comet assay was used to measure the DNA damage in leukocytes. We measured the activity of superoxide dismutase (SOD), catalase, glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PD), and glutathione-S-transferase (GST) as well as the concentration of malondialdehyde (MDA), and the value of the total antioxidant capacity. The level of PbB was significantly higher in the examined subgroups than in the control group. The percentage of DNA in the tail was significantly higher in the LE, ME, and HE subgroups than in the control group by 10% ( p = 0.001), 15% ( p < 0.001), and 20% ( p < 0.001), respectively. The activity of GR was significantly lower in the LE and ME subgroups than in the control group by 25% ( p = 0.007) and 17% ( p = 0.028), respectively. The activity of G6PD was significantly lower in the ME subgroup by 25% ( p = 0.022), whereas the activity of GST was significantly higher in the HE subgroup by 101% ( p = 0.001) than in the control group. Similarly, the activity of SOD was significantly higher in the LE and ME subgroups by 48% ( p = 0.026) and 34% ( p = 0.002), respectively. The concentration of MDA was significantly higher in the LE, ME, and HE subgroups than in the control group by 43% ( p = 0.016), 57% ( p < 0.001), and 108% ( p < 0.001), respectively. Occupational lead exposure induces DNA damage, including oxidative damage, in human leukocytes. The increase in DNA damage was accompanied by an elevated intensity of oxidative stress.

scholarly journals Oxidative lipid, protein, and DNA damage as oxidative stress markers in vascular complications of diabetes mellitus

2011 ◽  
Vol 34 (3) ◽  
pp. 163 ◽  
Author(s):  
Omur Tabak ◽  
Remise Gelisgen ◽  
Hayriye Erman ◽  
Fusun Erdenen ◽  
Cüneyt Muderrisoglu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Vascular Complications ◽  
Diabetic Group ◽  
Control Group ◽  
Diabetic Patients ◽  
Serum Samples ◽  
Type 2 Diabetic Patients

Purpose: The purpose of this study was to determine the effects of diabetic complications on oxidation of proteins, lipids, and DNA and to investigate the relationship between oxidative damage markers and clinical parameters. Methods: The study group consisted of 69 type 2 diabetic patients (20 patients without complication, 49 patients with complication) who attended internal medicine outpatient clinics of Istanbul Education and Research Hospital and 19 healthy control subjects. In serum samples of both diabetic patients and healthy subjects, 8-hydroxy-2’deoxyguanosine (8-OHdG), as a marker of oxidative DNA damage, Nε-(hexanoyl)lysine (HEL) and 15-F2t-iso-prostaglandin (15-F2t-IsoP). as products of lipooxidative damage, advanced oxidation protein products (AOPP), as markers of protein damage, and paraoxonase1 (PON1) as antioxidant were studied. Results: 15-F2t-IsoP (p < 0.005) and AOPP (p < 0.001) levels were significantly higher in diabetic group than control group while there were no significant differences in levels of 8-OHdG and HEL between the two groups. AOPP (p < 0.001) and 8-OHdG (p < 0.001) were significantly higher in diabetic group with complications compared to diabetic group without complications. Conclusions: Increased formation of free radicals and oxidative stress, under conditions of hyperglycaemia, is one of the probable causes for evolution of complications in diabetes mellitus. Our study supports the hypothesis that oxidant/antioxidant balance is disturbed in diabetic patients.

Paternal impacts on development: identification of genomic regions vulnerable to oxidative DNA damage in human spermatozoa

2019 ◽  
Vol 34 (10) ◽  
pp. 1876-1890 ◽  
Author(s):  
M J Xavier ◽  
B Nixon ◽  
S D Roman ◽  
R J Scott ◽  
J R Drevet ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Male Infertility ◽  
Oxidative Damage ◽  
Oxidative Dna Damage ◽  
Human Spermatozoa ◽  
Research Centre ◽  
Environmental Toxicants ◽  
Next Generation ◽  
Genomic Regions

Abstract STUDY QUESTION Do all regions of the paternal genome within the gamete display equivalent vulnerability to oxidative DNA damage? SUMMARY ANSWER Oxidative DNA damage is not randomly distributed in mature human spermatozoa but is instead targeted, with particular chromosomes being especially vulnerable to oxidative stress. WHAT IS KNOWN ALREADY Oxidative DNA damage is frequently encountered in the spermatozoa of male infertility patients. Such lesions can influence the incidence of de novo mutations in children, yet it remains to be established whether all regions of the sperm genome display equivalent susceptibility to attack by reactive oxygen species. STUDY DESIGN, SIZE, DURATION Human spermatozoa obtained from normozoospermic males (n = 8) were split into equivalent samples and subjected to either hydrogen peroxide (H2O2) treatment or vehicle controls before extraction of oxidized DNA using a modified DNA immunoprecipitation (MoDIP) protocol. Specific regions of the genome susceptible to oxidative damage were identified by next-generation sequencing and validated in the spermatozoa of normozoospermic males (n = 18) and in patients undergoing infertility evaluation (n = 14). PARTICIPANTS/MATERIALS, SETTING, METHODS Human spermatozoa were obtained from normozoospermic males and divided into two identical samples prior to being incubated with either H2O2 (5 mm, 1 h) to elicit oxidative stress or an equal volume of vehicle (untreated controls). Alternatively, spermatozoa were obtained from fertility patients assessed as having high basal levels of oxidative stress within their spermatozoa. All semen samples were subjected to MoDIP to selectively isolate oxidized DNA, prior to sequencing of the resultant DNA fragments using a next-generation whole-genomic sequencing platform. Bioinformatic analysis was then employed to identify genomic regions vulnerable to oxidative damage, several of which were selected for real-time quantitative PCR (qPCR) validation. MAIN RESULTS AND THE ROLE OF CHANCE Approximately 9000 genomic regions, 150–1000 bp in size, were identified as highly vulnerable to oxidative damage in human spermatozoa. Specific chromosomes showed differential susceptibility to damage, with chromosome 15 being particularly sensitive to oxidative attack while the sex chromosomes were protected. Susceptible regions generally lay outside protamine- and histone-packaged domains. Furthermore, we confirmed that these susceptible genomic sites experienced a dramatic (2–15-fold) increase in their burden of oxidative DNA damage in patients undergoing infertility evaluation compared to normal healthy donors. LIMITATIONS, REASONS FOR CAUTION The limited number of samples analysed in this study warrants external validation, as do the implications of our findings. Selection of male fertility patients was based on high basal levels of oxidative stress within their spermatozoa as opposed to specific sub-classes of male factor infertility. WIDER IMPLICATIONS OF THE FINDINGS The identification of genomic regions susceptible to oxidation in the male germ line will be of value in focusing future analyses into the mutational load carried by children in response to paternal factors such as age, the treatment of male infertility using ART and paternal exposure to environmental toxicants. STUDY FUNDING/COMPETING INTEREST(S) Project support was provided by the University of Newcastle’s (UoN) Priority Research Centre for Reproductive Science. M.J.X. was a recipient of a UoN International Postgraduate Research Scholarship. B.N. is the recipient of a National Health and Medical Research Council of Australia Senior Research Fellowship. Authors declare no conflict of interest.

Impact of the Ser326Cys polymorphism of the OGG1 gene on the level of oxidative DNA damage in patients with colorectal cancer

2018 ◽  
Vol 90 (2) ◽  
pp. 13-15 ◽  
Author(s):  
Jacek Kabzinski ◽  
Anna Walczak ◽  
Adam Dziki ◽  
Michał Mik ◽  
Ireneusz Majsterek
Keyword(s):  
Colorectal Cancer ◽  
Dna Damage ◽  
Oxidative Damage ◽  
Oxidative Dna Damage ◽  
Excision Repair ◽  
Genetic Material ◽  
Control Group ◽  
Ogg1 Gene ◽  
Increased Risk ◽  
Ser326cys Polymorphism

As a result of reactive oxygen species operation, cell damage occurs in both cellular organelles and molecules, including DNA. Oxidative damage within the genetic material can lead to accumulation of mutations and consequently to cancer transformation. OGG1 glycosylase, a component of the Base Excision Repair (BER) system, is one of the enzymes that prevents excessive accumulation of 8-oxoguanine (8-oxG), the most common compound formed by oxidative DNA damage. In case of structural changes of OGG1 resulting from polymorphic variants, we can observe a significant increase in the concentration of 8-oxG. Linking individual polymorphisms to DNA repair systems with increased risk of colorectal cancer will allow patients to be classified as high risk and included in a prophylactic program. The aim of the study was to determine the level of oxidative DNA damage and to analyze the distribution of Ser326Cys polymorphism of the OGG1 gene in a group of patients with colorectal cancer and in a control group in the Polish population. Material and methodology. DNA was isolated from the blood of 174 patients with colorectal cancer. The control group consisted of 176 healthy individuals. The level of oxidative damage was determined by analyzing the amount of 8-oxguanine using the HT 8-oxo-dG ELISA II Kit. Genotyping was performed via the TaqMan method. Results. The obtained results indicate that Ser326Cys polymorphism of the OGG1 gene increases the risk of RJG and is associated with significantly increased levels of 8-oxoguanine. Conclusions. Based on the results obtained, we conclude that Ser326Cys polymorphism of the OGG1 gene may modulate the risk of colorectal cancer by increasing the level of oxidative DNA damage.

Selective Damage to Antioxidant Gene Promoters in FA Cells

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2413-2413
Author(s):  
Wei Du ◽  
Reena Rani ◽  
Jared Sipple ◽  
Jonathan Schick ◽  
Qishen Pang
Keyword(s):  
Oxidative Stress ◽  
Bone Marrow ◽  
Dna Damage ◽  
Oxidative Damage ◽  
Oxidative Dna Damage ◽  
Defense Genes ◽  
Atpase Subunit ◽  
Promoter Complex ◽  
Anti Oxidant ◽  
Promoter Dna

Abstract Abstract 2413 Oxidative stress has been implicated in the pathogenesis of many human diseases including Fanconi anemia (FA), a genetic disorder associated with bone marrow failure and progression to leukemia and other cancers. Here we show that several major anti-oxidant defense genes, including Glutathione peroxidase 1, Peroxiredoxin 3, Thioredoxin reductase 1, Superoxide dismutases 1, NAD(P)H:quinone oxireductase and Catalase, are down-regulated in bone marrow cells of FA patients. This gene down-regulation is selectively associated with increased oxidative DNA damage in the promoters of these anti-oxidant defense genes. Further, we show that both increased initial damage and reduced repair rate contribute to augmented oxidative DNA damage in FA cells. Using cell-based assays to assess promoter activity and damage repair kinetics, we demonstrate that FA proteins function to protect the promoter DNA from oxidative damage. Mechanistically, FA proteins appeared to act in concert with Brg1, a chromatin-remodeling ATPase subunit of the BAF complex. Specifically, Brg1 binds to the promoters of the anti-oxidant defense genes in steady state. Upon challenge with oxidative stress, FANCA and FANCD2 proteins are recruited to the promoter DNA, which correlates with significant increase in the binding of Brg1 within the promoter regions. Intriguingly, the formation of the FA-Brg1-promoter complex results in a marked decrease in nuclease hypersensitivity and oxidative damage in the promoter DNA in normal cells compared to FA cells. Finally, disassociation of the FA proteins from the Brg1-promoter complex parallels Pol II loading, suggesting a regulatory role for the FA proteins in transcription. Taken together, the study identifies a role of FA proteins in protecting anti-oxidant genes from oxidative damage. Disclosures: No relevant conflicts of interest to declare.

Mixture Analysis of Associations between Occupational Exposure to Polycyclic Aromatic Hydrocarbons and Sperm Oxidative DNA Damage

2021 ◽  
Author(s):  
Hueiwang Anna Jeng ◽  
Sinjini Sikdar ◽  
Chih-Hong Pan ◽  
Guo-Ping Chang-Chien
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Oxidative Damage ◽  
Oxidative Dna Damage ◽  
Selection Process ◽  
Coke Oven ◽  
Breathing Zone ◽  
Suggestive Association ◽  
Polycyclic Aromatic ◽  
Coke Oven Workers

Abstract Objective This study aimed to determine (i) associations between levels of the polycyclic aromatic hydrocarbon (PAH) mixture with 16 targeted PAH compounds in the personal breathing zone area and sperm oxidative DNA damage, (ii) associations between levels of individual PAH compounds and sperm oxidative DNA damage, (iii) oxidative stress as the mode of action for the genotoxic effects on sperm, and (iv) any dose–response relationship between exposure to the PAH mixture and/or individual PAH compounds and sperm oxidative DNA damage. Methods Sixteen targeted PAH compounds in the personal breathing zone area of 38 coke-oven workers and 24 control subjects were quantified using gas chromatography–mass spectrometry. Sperm oxidative damage and status were evaluated by measuring levels of sperm 7,8-dihydro-8-oxoguanie (8-oxodGuo), seminal malondialdehyde (MDA) and seminal reactive oxygen species (ROS). Bayesian kernel machine regression with hierarchical variable selection process was employed to determine associations of the PAH mixture and the biomarkers of sperm oxidative damage. A novel grouping approach needed for the hierarchical variable selection process was developed based on PAH bay region and molecular weight. Results The PAH mixture exhibited a positive trend with increased sperm 8-oxodGuo levels at their lower percentiles (25th–50th). The exposure of the PAH mixture was associated with increased MDA levels in sperm. Bay and bay-like regions of the PAH mixture were the most important group for estimating the associations between the PAH mixture and sperm oxidative stress status. Benzo[a]anthracene was the main individual PAH compound that was associated with increased MDA levels. Conclusion Sperm oxidative DNA damage induced by occupational exposure to the PAH mixture had a suggestive association with increased MDA levels in coke-oven workers. Finally, the study identified that the individual PAH compound, benzo[a]anthracene, was the primary driver for the suggestive association between the PAH mixture and sperm oxidative damage.

scholarly journals MEASUREMENT OF DNA DAMAGE, OXIDATIVE STRESS, AND GENE EXPRESSION OF β-CATENIN AND P53 GENES IN LIVER AND BRAIN OF MALE MICE RECEIVING MONOSODIUM L-GLUTAMATE MONOHYDRATE

2020 ◽  
pp. 127-132
Author(s):  
NOHA IBRAHIM SAID SALEM ◽  
HANAN R.H. MOHAMED ◽  
AREEG MOHAMED ABD-ELRAZEK
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Quantitative Polymerase Chain Reaction ◽  
Significant Decline ◽  
Control Group ◽  
Group I ◽  
Significant Difference ◽  
P53 Genes

Introduction: Monosodium L-glutamate (MSG) monohydrate is a widespread nutritional additive and flavoring agent frequently consumed all over the world. In this study, we investigate the action of daily oral intake of MSG monohydrate in vivo using mammalian systems. Methods: Mice divided as follows: Group I (normal control), Group II, and Group III treated with MSG for 2 and 4 weeks, respectively. Brain and liver dissected out for the detection of fragmented DNA, DNA damage, and assay of oxidative stress markers. Moreover, expression levels of ß-Cat and p53 genes were measured by a real-time quantitative polymerase chain reaction. Results: The results showed a significant difference in MSG-treated group at the 2-time intervals than the control one regarding parameters of oxidative stress, and these were accompanied by a significant decline in glutathione (GSH) and a ratio of oxidized and reduced GSH in both tissues. Significant elevation of laddered DNA and oxidative DNA damage was observed in groups treated with MSG. In addition, a significant decline in gene expression of ß-Catenin in liver and brain tissues with elevations in the gene expression of p53 in the brain. Furthermore, the p53 gene in liver tissue was significantly upregulated in mice administered MSG for 15 days and was downregulated after 30 days of MSG intake compared with the control. Conclusion: According to our results, oral consumption of MSG leads to oxidative stress-mediated DNA damage and apoptosis.

scholarly journals Effects of Heavy Metal Exposure on Shipyard Welders: A Cautionary Note for 8-Hydroxy-2’-Deoxyguanosine

2019 ◽  
Vol 16 (23) ◽  
pp. 4813 ◽  
Author(s):  
Su ◽  
Pan ◽  
Hsu ◽  
Lai
Keyword(s):  
Oxidative Stress ◽  
Heavy Metal ◽  
Dna Damage ◽  
Oxidative Damage ◽  
Oxidative Dna Damage ◽  
Hazard Identification ◽  
Metal Exposure ◽  
Welding Fumes ◽  
Heavy Metal Exposure ◽  
The Relationship

Oxidative stress plays a crucial role in the development of diseases induced by welding fumes. To our knowledge, little information is available on the relationship between multiple heavy metal exposure and oxidative stress in welders. We assessed the relationship between multiple heavy metal exposure and oxidative damage by analyzing 174 nonsmoking male welders in a shipyard. Urinary metals were used as the internal dose of exposure to metals in welding fumes, and urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG) was used as an oxidative DNA damage marker. The relationship between workers’ metal levels and 8-OHdG was estimated using a multiple linear regression model. The geometric mean levels of urinary chromium (Cr), nickel (Ni), cadmium (Cd), and lead (Pb) were considerably higher in welders than in controls. Urinary Cr and Ni were determined as effective predictors of urinary 8-OHdG levels after adjusting for covariates. Oxidative DNA damage was associated with both Cr and Ni of welding fume exposure in shipyard welders (Ln Cr: β = 0.33, 95%C.I. = 0.16–0.49; Ln Ni: β = 0.27, 95%C.I. = 0.12–0.43). In this study, we investigated the significantly positive relationship between urinary metals (especially Cr and Ni) and 8-OHdG in nonsmoking shipyard welders. Moreover, the use of particulate respirators did not reduce metal exposure and oxidative damage. Therefore, we infer that hazard identification for welders should be conducted.

scholarly journals Effect of Coal Dust Exposure on the SOD Activity and the Oxidative DNA Damage in Asthmatic Mice

2019 ◽  
Vol 11 (2) ◽  
pp. 159-66
Author(s):  
Windy Yuliana Budianto ◽  
Husnul Khotimah ◽  
Eko Suhartono
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Coal Dust ◽  
Negative Control ◽  
Dust Exposure ◽  
Dust Particles ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Sod Activity

BACKGROUND: Coal dust is known to trigger hypersensitivity and inflammation of the respiratory tract as it increases oxidative stress leading to asthma. To date, the relationship of coal dust exposure in the pathomechanism of asthma remains unclear. This study was aimed to examine the effect of coal dust exposure on the superoxide dismutase (SOD) activity and the oxidative DNA damage indicated by increased serum 8-hydroxy-2' -deoxyguanosine (8-OHdG) in asthmatic mice.METHODS: Twenty-four female balb/c mice were divided into four groups. The first group was the control group. The second group was the negative control group which composed of mice exposed to coal dust particles. The third group was composed of ovalbumin (OVA)-sensitized mice. The fourth group was composed of OVA-sensitized mice and exposed to coal dust particles. The inflammatory process was identified by serum interleukin (IL)-13 concentration using Enzyme-linked Immunosorbent Assay (ELISA) method. Meanwhile, the oxidative stress was examined by measuring the SOD activity using the Nitro Blue Tetrazolium (NBT) method, and the 8-OHdG concentration was quantified by ELISA method.RESULTS: There was an increasing IL-13 in OVAtreated coal dust exposed group along with the increment of 8-OHdG (statistically not significant). SOD activity measured in serum was decreased in all groups (p>0.05). Combination of OVA and coal dust showed the worst effect on IL-13, 8-OHdG and SOD activity.CONCLUSION: Coal dust exposure for four weeks does not adequately induce the oxidative DNA damage in asthmatic mice.KEYWORDS: asthma, coal dust, IL-13, SOD, 8-OHdG

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.

Chemoprotective Effects of Propolis on Aflatoxin B1-Induced Hepatotoxicity in Rats: Oxidative Damage and Hepatotoxicity by Modulating TP53, Oxidative Stress

2020 ◽  
Vol 17 (3) ◽  
pp. 191-199
Author(s):  
Seval Yilmaz ◽  
Fatih Mehmet Kandemir ◽  
Emre Kaya ◽  
Mustafa Ozkaraca
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Oxidative Damage ◽  
Aflatoxin B1 ◽  
Tp53 Gene ◽  
Control Group ◽  
Glutathione S Transferase ◽  
Gene Expressions ◽  
Cat Gene ◽  
Gst Activity

Objective: This study aimed to detect hepatic oxidative damage caused by aflatoxin B1 (AFB1), as well as to examine how propolis protects against hepatotoxic effects of AFB1. Method: Rats were split into four groups as control group, AFB1 group, propolis group, AFB1+ propolis group. Results: There was significant increase in malondialdehyde (MDA) level and tumor suppressor protein (TP53) gene expression, Glutathione (GSH) level, Catalase (CAT) activity, CAT gene expression decreased in AFB1 group in blood. MDA level and Glutathione-S-Transferase (GST) activity, GST and TP53 gene expressions increased in AFB1 group, whereas GSH level and CAT activity alongside CAT gene expression decreased in liver. AFB1+propolis group showed significant decrease in MDA level, GST activity, TP53 and GST gene expressions, GSH level and CAT activity and CAT gene expression increased in liver compared to AFB1 group. Conclusion: These results suggest that propolis may potentially be natural agent that prevents AFB1- induced oxidative stress and hepatotoxicity.

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