Analysis of Genetic Damage in Lymphocytes of Former Uranium Processing Workers

2015 ◽  
Vol 147 (1) ◽  
pp. 17-23 ◽  
Author(s):  
Friedo Zölzer ◽  
Renata Havránková ◽  
Zuzana Freitinger Skalická ◽  
Andrea Rössnerová ◽  
Radim J. Šrám

The frequency of cells containing micronuclei (MN) and the presence of centromeres in these MN were analyzed in lymphocytes of 98 men from Southern Bohemia. Forty-six of them had worked at the uranium processing plant ‘MAPE Mydlovary' which was closed in 1991, and 52 men were controls from the same area. FISH using human pan-centromeric chromosome paint was employed to detect centromere-positive (CEN+) and -negative (CEN-) MN. A total of 1,000 binucleated cells (BNC) per participant were analyzed after cytochalasin B treatment. All BNC with MN (CEN+ or CEN-) were recorded. No differences were found between formerly exposed workers and the control group, neither in the total frequency of cells with MN per 1,000 BNC (mean levels ± SD, 9.1 ± 3.1 and 9.8 ± 2.5, respectively) nor in the percentage of CEN- MN, which were equal (50 ± 18 and 49 ± 17, respectively). Also, there was no difference between individuals living in the 3 villages closest to the uranium processing plant and those living further away. Considering the fact that effective doses of the workers at MAPE Mydlovary were overall similar to those of former uranium miners in whom higher frequencies of CEN- MN have been found more than 10 years after they had finished working underground, these results are somewhat surprising. A more detailed analysis of the exposures indicates that uranium miners received a greater percentage of their effective dose from the inhalation of radon and its daughters, whereas uranium processing workers received it from the incorporation of long-lived radioactive nuclides such as uranium. If, as has been suggested before, the higher level of DNA damage in miners is due to induced genomic instability, then this phenomenon may be related to radon exposure rather than exposure to uranium.

2020 ◽  
Vol 9 (5) ◽  
pp. 661-668
Author(s):  
Xiumei Xing ◽  
Zhini He ◽  
Ziwei Wang ◽  
Ziying Mo ◽  
Liping Chen ◽  
...  

Abstract To explore the epigenetic alterations in response to DNA damage following polycyclic aromatic hydrocarbons (PAHs) exposure and the crosstalk between different epigenetic regulations, we examined trimethylated Lys 36 of histone H3 (H3K36me3) and methylation of ‘long interspersed element-1 (LINE-1)’ and ‘O 6-methylguanine-DNA methyltransferase (MGMT)’ in peripheral blood lymphocytes (PBLCs) of 173 coke oven workers (PAH-exposed group) and 94 non-exposed workers (control group). The PAH-exposed group showed higher internal PAH exposure level, enhanced DNA damage and increased MGMT expression (all P < 0.001). Notably, the methylation of LINE-1 and MGMT decreased by 3.9 and 40.8%, respectively, while H3K36me3 level was 1.7 times higher in PBLCs of PAH-exposed group compared to control group (all P < 0.001). These three epigenetic marks were significantly associated with DNA damage degree (all P < 0.001) and PAH exposure level in a dose–response manner (all P < 0.001). LINE-1 hypomethylation is correlated with enhanced H3K36me3 modification (β = −0.198, P = 0.002), indicating a synergistic effect between histone modification and DNA methylation at the whole genome level. In addition, MGMT expression was positively correlated with H3K36me3 modification (r = 0.253, P < 0.001), but not negatively correlated with MGMT methylation (r = 0.202, P < 0.05). The in vitro study using human bronchial epithelial cells treated with the organic extract of coke oven emissions confirmed that H3K36me3 is important for MGMT expression following PAH exposure. In summary, our study indicates that histone modification and DNA methylation might have synergistic effects on DNA damage induced by PAH exposure at the whole genome level and H3K36me3 is more essential for MGMT expression during the course.


2017 ◽  
Vol 68 (3) ◽  
pp. 228-235 ◽  
Author(s):  
Gordana Brozović ◽  
Nada Oršolić ◽  
Ružica Rozgaj ◽  
Fabijan Knežević ◽  
Anica Horvat Knežević ◽  
...  

AbstractThe aim of this study was to evaluate the DNA damage and repair in kidney cells of Swiss albino mice after repeated exposure to sevoflurane and isoflurane and compare their detrimental effects. We used the alkaline comet assay to establish the genetic damage and measured three parameters: tail length, tail moment, and tail intensity of comets. These parameters were measured immediately after exposure to the above mentioned inhalation anaesthetics, two hours, six hours, and 24 hours later and were compared with the control group. Mean values of all three parameters were significantly higher in experimental groups compared to the control group. DNA damage in kidney cells of mice exposed to sevoflurane increased continuously before it reached its peak 24 hours after exposure. Isoflurane induced the highest DNA damage two hours after exposure. Levels of DNA damage recorded 24 h after cessation of exposure to both tested compounds suggest that sevoflurane was slightly more genotoxic than isoflurane to kidney cells of mice. According to these results, the currently used volatile anaesthetics sevoflurane and isoflurane are able to damage DNA in kidney cells of mice. Such findings suggest a possibility for similar outcomes in humans and that fact must be taken into account in everyday clinical practice.


1998 ◽  
Vol 45 (2) ◽  
pp. 605-610 ◽  
Author(s):  
J Palus ◽  
E Dziubałtowska ◽  
K Rydzyński

Single-strand breaks (SSB) and DNA repair were detected in peripheral lymphocytes derived from workers of a furniture factory in a non-polluted region of Poland. The workers were exposed to wood dust (n = 19), or to the dust and varnishes or lacquers together (n = 5). Four groups were studied simultaneously: (a) exposed workers smokers of cigarettes (n = 14), (b) nonexposed smokers--control (n = 14), (c) exposed workers' nonsmokers (n = 14), (d) exposed nonsmokers (n = 10). In exposed workers DNA SSB and DNA repair were statistically significantly increased. DNA SSB was clearly higher in the smoking workers than in the smoking controls. Cigarette smoking itself has produced no evident increase in the frequency of DNA SSB in the control group. Occupational exposure had a significant effect on DNA repair in non stimulated lymphocytes both in smoking and nonsmoking workers.


2021 ◽  
Vol 19 (1) ◽  
pp. 01-05
Author(s):  
K Sriambika ◽  

Background: Formaldehyde (FA) is the reactive and simplest of all the aldehydes. It is used as a preservative in anatomy, pathology and forensic laboratories. The international agency for research on cancer has classified FA as a carcinogen that can cause nasopharyngeal carcinoma, Leukaemia, Liver and pancreatic cancer. Objective And Method: The aim of the study was to assess the DNA damage in peripheral blood lymphocytes and in buccal cells by Micronucleus assay in Formalin exposed workers of Anatomy, Pathology and Forensic laboratories and compare with the control group, and also to analyze the relationship between frequency of Micronuclei and duration of exposure to formalin. Results: The mean and standard deviation (SD) of micronuclei in peripheral blood of exposed was 8.35 and in controls was 4.18. There was a significant increase in the frequency of MN in exposed group when compared with the comparison group (p<0. 5876). Pearson’s correlation test showed a positive correlation between the years of FA exposure and the number of micronuclei in buccal cells and peripheral blood indicating that DNA damage due to FA was directly proportional to the duration of exposure (r=0.8, 0.9). Conclusion: The present study was done to assess the DNA damage in people who were exposed to FA and a control group not exposed to FA by buccal cell and peripheral blood Micronucleus Assay. There was a significant increase in the MN in people exposed to FA which was directly proportional to the duration of exposure.


2018 ◽  
Vol 76 (3) ◽  
pp. 115-124 ◽  
Author(s):  
Puthan Variyam Vidya ◽  
Kumari Chidambaran Chitra

Abstract The purpose of the present study is to extend knowledge on the adverse effects of nanoparticles by evaluating genotoxicity as environmental risk assessment in Oreochromis mossambicus. Fish were exposed to sublethal concentrations of the selected nanoparticles, namely silicon dioxide (SiO2NPs-12mg/L), aluminium oxide (Al2O3NPs-4mg/L), titanium dioxide (TiO2NPs-16.4mg/L) and iron oxide (Fe3O4NPs-15mg/L) for short-term (24, 72 and 96 h) and long-term durations (15, 30 and 60 days). Genetic damages such as cytoplasmic, nuclear and DNA damage were measured in the erythrocytes of fish by using standard genotoxicity tests such as micronucleus test and comet assay. The frequencies of micronuclei along with nuclear and cytoplasmic abnormalities were scored and compared with the control group. The intensity of micronuclei along with other nuclear and cytoplasmic anomalies are found to be increased significantly (p<0.05) in time-dependent manner in all exposure groups when compared to the control group, thereby indicating chromosomal damage as a result of contact with nanoparticles. The tail length and percent of tail DNA within the comet significantly (p<0.05) increased in time-dependant manner after exposure to all nanoparticles, demonstrating an increase in DNA damage. Taken together, by using micronucleus test and comet assay, it is evident that the selected nanoparticles at sublethal concentrations induced genetic damage in Oreochromis mossambicus.


2020 ◽  
Vol 9 (3) ◽  
pp. 302-307
Author(s):  
Congcong Zhao ◽  
Yuanchen Xie ◽  
Xiaoshan Zhou ◽  
Qiao Zhang ◽  
Na Wang

Abstract Objective To explore the genetic damage caused by different tar levels in the human body. Methods The subjects were divided into high, medium and low (12 mg, 8 mg, 5 mg) tar groups according to the tar levels. Nonsmoking populations served as a control group. 2 ml of peripheral blood was collected on the 10th day after morning fasting. Oxidative and genetic toxicological damage indicators were analysed with enzyme-linked immunosorbent assay, cytokinesis-block micronucleus assay in human lymphocyte and single cell gel electrophoresis. Results The distribution of hOGG1 concentration was significantly different within all groups, P &lt; 0.01. The concentrations of cotinine, 8-OHdG and Rap-2b were significantly differences between control and medium tar group, control and high tar group, low and medium tar group and low and high tar group, respectively, P &lt; 0.05. The level of PAH-DNA adducts was not significantly changed in the middle tar group and high tar group, P &gt; 0.05. The level of CRP was significantly changed between control and high tar group, low and high tar group and medium and high tar group, respectively, P &lt; 0.0001. The rate of comet tailing was significantly different between all groups. The rate of micronucleus cells was not significantly different between all groups. Conclusions The increase of tar content could increase the DNA damage to a certain extent, so the intake of tar content should be monitored.


2013 ◽  
Vol 33 (1) ◽  
pp. 14-21 ◽  
Author(s):  
MI Turan ◽  
A Cayir ◽  
N Cetin ◽  
H Suleyman ◽  
I Siltelioglu Turan ◽  
...  

This study investigated the effects of thiamine pyrophosphate (TPP) at dosages of 10 and 20 mg/kg on oxidative stress induced in rat brain tissue with cisplatin and compared this with thiamine. Cisplatin neurotoxicity represents one of the main restrictions on the drug being given in effective doses. Oxidative stress is considered responsible for cisplatin toxicity. Our results showed that cisplatin increased the levels of oxidant parameters such as lipid peroxidation (thio barbituric acid reactive substance (TBARS)) and myeloperoxidase (MPO) in brain tissue and suppressed the effects of antioxidants such as total glutathione (GSH) and superoxide dismutase (SOD). TPP, especially at a dosage of 20 mg/kg, significantly reduced TBARS and MPO levels that increase with cisplatin administration compared with the thiamine group, while TPP significantly increases GSH and SOD levels. In addition, the level of 8-Gua (guanine), a product of DNA damage, was 1.7 ± 0.12 8-hydroxyl guanine (8-OH Gua)/105 Gua in brain tissue in the control group receiving cisplatin, compared with 0.97 ± 0.03 8-OH Gua/105 Gua in the thiamine pyrophosphate (20 mg/kg) group and 1.55 ± 0.11 8-OH Gua/105 Gua in the thiamine (20 mg/kg) group. These results show that thiamine pyrophosphate significantly prevents oxidative damage induced by cisplatin in brain tissue, while the protective effect of thiamine is insignificant.


Author(s):  
Anastasiya G. Khotuleva ◽  
Mariya S. Kozyreva

Introduction. The most susceptible to lead is the hematopoietic system of hematopoietic organs due to lead inhibition of heme and globin synthesis and cytotoxic effect on the membrane of Mature red blood cells. The aim of study was to evaluate the informative value of the study of erythrocyte and reticulocyte parameters determined on modern hematological analyzers in patients working in contact with lead during medical and biological monitoring. Materials and methods. 45 employees of the lead battery processing plant and 30 persons of control group were examined. The level of lead in the blood was determined by atomic absorption spectrometry, δ-ALA in the urine-by the reaction of pyrol formation with acetylacetone in terms of gram of creatinine, the study of hematological parameters was performed on a Sysmex HT-2000i analyzer. Statistical processing of the results was performed using the program STATISTICA 10.0. Results. Significant changes in erythrocytic (RDW) and reticulocytic (RET, IRF, LFR, MFR, HFR, RET-He) parameters, erythropoietin in workers in contact with lead compared to the control group, changes in MCV, MCH, RDW, RET indicators in the group working in dynamics after 2 years were revealed. Associations of hematological parameters with biomarkers of exposure and effect (lead level in blood and ALA in urine) were revealed. Conclusions. Assessment of erythrocyte (MCV, MCH, RDW) and reticulocyte parameters (RET% and their distribution by maturity) in dynamics during periodic medical examinations of workers in contact with lead allows us to detect the development of hematological disorders at early stages.


2019 ◽  
Vol 19 (6) ◽  
pp. 803-808 ◽  
Author(s):  
Luigi Vimercati ◽  
Luigi De Maria ◽  
Francesca Mansi ◽  
Antonio Caputi ◽  
Giovanni M. Ferri ◽  
...  

Background: Thyroid diseases occur more frequently in people exposed to ionizing radiation, but the relationship between occupational exposure to ionizing radiation and thyroid pathologies still remains unclear. Objective: To evaluate the prevalence of thyroid diseases in healthcare workers exposed to low-level ionizing radiation compared with a control group working at the University Hospital of Bari, Southern Italy, and living in the same geographical area, characterized by mild iodine deficiency. Methods: We ran a cross-sectional study to investigate whether healthcare workers exposed to ionizing radiation had a higher prevalence of thyroid diseases. Four hundred and forty-four exposed healthcare workers (241 more exposed, or “A Category”, and 203 less exposed, or “B Category”) and 614 nonexposed healthcare workers were enrolled during a routine examination at the Occupational Health Unit. They were asked to fill in an anamnestic questionnaire and undergo a physical examination, serum determination of fT3, fT4 and TSH, anti-TPO ab and anti-TG ab and ultrasound neck scan. Thyroid nodules were submitted to fine needle aspiration biopsy when indicated. Results: The prevalence of thyroid diseases was statistically higher in the exposed workers compared to controls (40% vs 29%, adPR 1.65; IC95% 1.34-2.07). In particular, the thyroid nodularity prevalence in the exposed group was approximately twice as high as that in the controls (29% vs 13%; adPR 2.83; IC95% 2.12-3.8). No statistically significant association was found between exposure to ionizing radiation and other thyroid diseases. Conclusion: In our study, mild ionizing radiation-exposed healthcare workers had a statistically higher prevalence of thyroid diseases than the control group. The results are likely due to a closer and more meticulous health surveillance programme carried out in the ionising radiation-exposed workers, allowing them to identify thyroid alterations earlier than non-exposed health staff.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Isela Álvarez-González ◽  
Scarlett Camacho-Cantera ◽  
Patricia Gómez-González ◽  
Michael J. Rendón Barrón ◽  
José A. Morales-González ◽  
...  

AbstractWe evaluated the duloxetine DNA damaging capacity utilizing the comet assay applied to mouse brain and liver cells, as well as its DNA, lipid, protein, and nitric oxide oxidative potential in the same cells. A kinetic time/dose strategy showed the effect of 2, 20, and 200 mg/kg of the drug administered intraperitoneally once in comparison with a control and a methyl methanesulfonate group. Each parameter was evaluated at 3, 9, 15, and 21 h postadministration in five mice per group, except for the DNA oxidation that was examined only at 9 h postadministration. Results showed a significant DNA damage mainly at 9 h postexposure in both organs. In the brain, with 20 and 200 mg/kg we found 50 and 80% increase over the control group (p ≤ 0.05), in the liver, the increase of 2, 20, and 200 mg/kg of duloxetine was 50, 80, and 135% in comparison with the control level (p ≤ 0.05). DNA, lipid, protein and nitric oxide oxidation increase was also observed in both organs. Our data established the DNA damaging capacity of duloxetine even with a dose from the therapeutic range (2 mg/kg), and suggest that this effect can be related with its oxidative potential.


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