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RESUMEN Introducción: La exposición ocupacional a residuos de minería de carbón puede generar un amplio rango de lesiones en el ADN potencialmente asociadas a procesos carcinogénicos y a otras enfermedades laborales. Objetivo: Evaluar el efecto genotóxico en el ADN de individuos ocupacionalmente expuestos a residuos de minería de carbón mediante la determinación de la frecuencia de micronúcleos (MN) en linfocitos y el posible efecto modulador del polimorfismo de reparo de DNA hOGG1Ser326Cys (rs.1052133). Metodología: Fueron estudiados 74 trabajadores expuestos (GE) y 74 individuos no expuestos de la población general como grupo control (GC), a los cuales se le realizaron las técnicas moleculares test de MN y genotipificación. Resultados: El valor promedio de la frecuencia de MN para el GE fue 8.8±4.9, mientras que el valor promedio para el GC fue de 2.9±4.0. En relación al tiempo de exposición y la frecuencia de MN, individuos con más de 19 años de exposición presentaron una frecuencia de MN mayor (13 - 20 MN) que los individuos entre 2 y 18 años de exposición (2-12 MN). La frecuencia de MN por áreas de trabajo, reveló que los individuos involucrados en actividades de minería presentaron una mayor frecuencia (11.3±3.4), seguidos de los involucrados en embarque (9.0±5.3) y trabajadores del área de acarreo (8.3±5.3). La actividad moduladora del polimorfismo hOGG1Ser326Cys sobre la frecuencia de MN en individuos del GE, evidenció una menor frecuencia (8.32± 4.70) en individuos portadores del polimorfismo Ser/Cys, Cys/Cys con relación a individuos portadores del genotipo Ser/ Ser (9.06± 4.95). Estos hallazgos sobre la posible actividad protectora de hOGG1Ser326Cys en poblaciones expuestas proveen nuevos datos sobre el posible efecto protector de este polimorfismo. Conclusiones: Los datos muestran que la exposición a residuos de minería de carbón genera efectos genotóxicos, y que estos daños son modulados por variantes genotípicas de los genes de reparación involucrados en la remoción de daño oxidativo.
ABSTRACT Introduction: Occupational exposure to coal mining residues can generate a wide range of DNA lesions potentially associated with carcinogenic processes and other work related diseases. Objetive: To evaluate the genotoxic effects in the DNA of individuals occupationally exposed to coal mining residues considering micronucleus formation in lymphocytes (MN) as endpoints for genotoxicity and the possible modulating effect of DNA repair polymorphism hOGG1Ser326Cys (rs. 1052133). Methodology: The studied population was comprised by 74 exposed workers (GE) and 74 office non-exposed referents from general population as a control group (CG). The mean frequency of MN for GE was 8.8 ± 4.9, while for GC was 2.9 ± 4.0. In regard to time of exposure and MN frequency, individuals over 19 years of exposure presented a higher frequency of MN (13-20 MN) than individuals between 2 and 18 years of exposure (2-12 MN). Results: Frequency of MN discriminated by working areas, revealed that the individuals involved in mining activities had a higher MN frequency (11.3 ± 3.4), followed by those involved in embarking (9.0 ± 5.3) and coal carrying activities (8.3 ± 5.3). Modulatory activity of the hOGG1Ser326Cys polymorphism on MN frequency in GE individuals, showed a lower frequency (8.32 ± 4.70) in individuals carrying the polymorphism Ser / Cys, Cys / Cys compared to Ser / Ser (9.06 ± 4.95) carriers. These findings on the possible protective activity of hOGG1Ser326Cys in exposed populations provide new data to the increasing evidence about the protective role of this polymorphism. Conclusions: Data obtained showed that exposure to coal mining residues generates genotoxic effects that could be modulated by genetic variants of repair genes involved in removal of oxidative damage.
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Polymorphism, Genetic , Occupational Exposure , Mining , Carbon , Open Dumps , EnvironmentABSTRACT
[ABSTRACT]AIM:Tostudytherelationshipbetweenhuman8-oxoguanineglycosylase1(hOGG1)gene Ser326Cys polymorphism and severity of coronary artery lesions in the patients with diabetes mellitus .METHODS: We retrospectively analyzed 323 patients with diabetic mellitus receiving coronary angiography .These patients underwent the test of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and were divided into Cys/Cys genotype (n=85), Ser/Ser genotype (n=121) and Ser/Cys genotype (n=117) according to the results of PCR-RFLP. All clinical data including history of diseases , complications and biochemical markers , such as blood glucose , blood lipids and so on, were recorded.hOGG1 mRNA and 8-hydroxydeoxyguanosine (8-OHdG) were measured by RT-PCR and ELISA, respectively.The results of coronary angiography such as number and severity of coronary artery with lesions were analyzed by 2 cardiovascular physicians .Gensini score and SYNTAX score were also detected by the unitary criteria .RE-SULTS:(1)8-OHdG in Cys/Cys genotype was higher than that in Ser /Ser genotype and Ser/Cys genotype (P0.05).(2)hOGG1 mRNA ex-pression in Cys/Cys genotype was lower than that in Ser/Ser genotype and Ser/Cys genotype (P0.05) was observed.(3)The probability of triple vessel lesions in Cys/Cys genotype was high and the probability of single vessel lesions in Ser /Cys genotype was low , but the difference among 3 genotypes was not statistically significant (P>0.05).(4)Gensini score and SYNTAX score in Cys/Cys genotype were 48.7 ±15.3 and 39.5 ±17.2, respectively, and the ratio of complex lesions in Cys/Cys genotype was 73.0%.These scores and the ratio of complex lesions were higher than the other 2 genotypes (P0.05).CONCLUSION:hOGG1 gene Ser326Cys polymorphism has relationship with coronary artery lesions in the patients with diabetes mellitus and Cys /Cys genotype might have some impacts on the severity of lesions .The mRNA expression of hOGG1 in the patients with diabetes mellitus carrying Cys/Cys genotype is lower than that in the patients carrying the other 2 genotypes , then decreases the abil-ity of identification and removal of 8-OHdG and the capacity of repairing DNA oxidative damage , and accelerates the devel-opment of atherosclerosis .
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Dysfunction of the human 8-oxoguanine DNA glycosylase (hOGG1) is closely related to development of lung neoplasms and other cancers.Polymorphisms in hOGG1 gene may alter glycosylase activity,thereby affect its repair capacity to the damaged DNA,contributing to carcinogenesis.Joint effects of hOGG1 and other DNA repair gene SNPs have showed complex gene-gene interactions may significantly contribute to people's lung cancer susceptibility.HOGG1 plays an important role in maintaining mitochondrial respiration thus affects tumor cell growth.
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OBJECTIVE To investigate DNA hypermethylation of human 8-hydroxyguanine glycosy-lase(hOGG1 )gene and and the level of oxidative stress and DNA oxidative damage relations with arse-nic poisoning.METHODS In ende mic coal-pollution-borne arsenism area,Xinren county,Guizhou Province,according to the diagnostic criteria of ende mic arsenism(WS /T21 1 -2001 ),207 people with ende mic arsenism were selected and divided into four groups(The arsenic exposure group:46 cases, mild arsenism group:46 cases,moderate arsenism group:60 cases and severe arsenism group:55 cases).64 residents were selected as controls in a village about 12 km away fro m the ende mic arsenism area.With the informed consent principle,peripheral blood of all respondents was collected in order to analyze DNA methylation.Methylation-specific poly merase chain reaction were respectively performed to analyze hOGG1 Hypermethylation in arsenism respondents.Che mical methods were performed on the activity of super oxide dis mutase (SOD)and glutathione peroxidase (GSH-Px),while the contents of malondialdehyde (MDA)in the blood of patients were measured,and the contents of 8-hydroxy-2′-deox-yguanine(8-OHdG)urine of patients were measured and analysed.On the basis of methylation status are divided into hOGG1 gene methylation group (34 cases)and hOGG1 gene no methylation group (237cases).Analysis was performd on hOGG1 gene DNA methylation and the relationship between oxi-dative stress and arsenic poisoning.RESULTS The positive rates of hypermethylation of hOGG1 were associated with the degree of arsenic poisonin (co mpared with control group,χ2 =23.916,P 0.05).CONCLUSION Coal arsenic exposure can cause hOGG1 gene high methylation and oxidation and anti-oxidation system imbalance,causing DNA oxidative damage,it is one of the reasons to pro mote the develop ment of arsenic poisoning occurred.
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DNA repair gene polymorphism can change the functions and efficiency of DNA repair,influence cancer susceptibility.Many studies have been reported that DNA damage repair gene polymorphisms may be related to cancer susceptibility mutation in a variety of tumors and plays an important role in the pathological process.In addition,DNA damage repair genes may interact with other genes,the combined effect of tumor occurrence,development.Lung cancer is the well-studied tumor in this respect.In this paper,DNA damage repair gene XRCC and hOGG1 polymorphisms biological characteristics,these gene single nucleotide polymorphisms as well as cancer susceptibility were reviewed to provide a theoretical basis for the tumor prevention,diagnosis and treatment.
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Objective: To establish a human lung cancer cell line A549 highly expressing human 8-oxoguanine-DNA glycosylase (hOGG1) by co-transfecting pcDNA 3.1 (+)/Myc-HisA-hOGG1 and PGL3 promoter, and to observe the biological behavior of the transfected cells. Methods: PcDNA3.1 (+)/Myc-His A-hOGG1 and PGL3 promoter were steadily co-transfected into A549 cells via mediation of Fu GENE 6 (transfected group); untransfected cells served as blank control and cells transfected with PGL3 + pcDNA3.1 (+)/Myc-HisA served as negative control. The hOGG1 mRNA expression in A549 cells was detected by Bio-luciferase activity and the hOGG1 protein expression by Western blotting analysis. Cells in the three groups were exposed to hyperoxia condition, and the morphological changes were observed by phase-contrast microscope. Comet cell rate and olive tail moment of cells were tested after different exposure periods. After exposure, the cells were incubated for 0, 60, 120, and 180 min, and the same indices were determined by modified comet assay; changes of DNA oxidative damage markers 8-hydroxy-desoxoguanosine (8-OHdG) was tested at the same time. Results: The bio-luciferase activity was stable in the co-transfected cells. Western blotting analysis showed that the expression of hOGG1 protein in co-transfected A549-T cells was significantly higher than those in the other two groups, indicating the successful establishment of hOGG1 highly expressing cells. Under the same hyperoxia condition, the morphological changes of transfected cells were greatly alleviated, and the Comet cell rate and olive tail moment of cells were obviously lower than those of the other two groups(P< 0.05). Transfected A549-T cells had significantly increased ability of DNA repair and shorter repair time compared with cells in the other two groups (P<0.05). Furthermore, the level of 8-OHdG in transfected A549-T cells was significantly lower than those of the other two groups under the same hyperoxia condition, indicating a significantly higher ability of DNA damage resisting and repair (P<0.05). Conclusion: High hOGG1 expression can decrease the cell sensitivity to DNA damage and improve the repair ability of cells.
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To observe the alteration in the expression of DNA repair enzymes hOGG1 and hMYHα and the change in 8-OHdG levels in the HBx gene-transfected cells HepG2/HBx and to explore the mechanisms of the HBV-associated hepatocellular carcinoma,the gene-transfected cells HepG2/HBx which stably expressed HBx was established,and the effect of HBx on the cell cycle and proliferation of HepG2 was examined.By using the β-actin as the interior control,real-time polymerase chain reaction (Real-time qPCR) was employed to quantitatively detect the expression of DNA repair enzymes hOGG1 and hMYHα in the HepG2/HBx,the control cells HepG2 and HepG2 transfected with pcDNA3.1 vector (HepG2/pDNA3.1).The 8-OHdG levels were determined by HPLC/ECD in the established gene-transfected cells HepG2/HBx and the control cells HepG2 and HepG2/pcDNA3.1.Our results showed that the expression of DNA repair enzyme hMYHα in the HepG2/HBx (0.021±0.007) was significantly lower than that of HepG2 (0.099±0.041) (P<0.05) and HepG2/pDNA3.1 (0.121±0.005) (P<0.05).However,the no significant differences existed in the expression of DNA repair enzyme hOGG1 among the three cell strains (P>0.05).The 8-OHdG level in the HepG2/HBx was significantly higher than that in HepG2 and HepG2/pcDNA3.1 (P<0.05).It is concluded that HBx gene may inhibit the expression of DNA repair enzyme hMYHα mRNA to impair the ability to repair the intracellular DNA oxidative damage,to increase the oxidative DNA-adduct 8-OHdG and to affect the nucleotide excision repair function,thus participate in the occurrence and development of hepatocellular carcinoma.
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BACKGROUND: DNA repair plays a crucial role in protecting the genome from cancer-causing agents. Therefore, a reduced DNA repair capacity can increase the susceptibility to cancer. The human OGG1 (hOGG1) gene encod es DNA glycosylase/apurinic lyase and excise 8-hydroxyguanine, one of the major premutagenic DNA lesions, which is produced by oxygen radical forming agents including smoking. Recently several polymorphisms in the hOGG1 gene were identified, and it is possible that these polymorphisms may affect the DNA repair capacity and thus modulate cancer susceptibility. The relationship between the codon 326 polymorphism (Ser to Cys) in the hOGG1 gene and lung cancer risk was investigated. MATERIALS AND METHOD: The Ser326Cys genotypes were determined using PCR-RFLP analysis in 299 primary lung cancer patients and 186 healthy controls who were frequency (case:control=3:2) matched according to age and sex. RESULT: The frequencies of the Ser326Cys genotypes (Ser/Ser, Ser/Cys and Cys/Cys) among cases (23.4%, 51.8%, and 24.7%, respectively) were not significantly different from those among the controls (22.6%, 52.1% and 25.3%, respectively). When the analyses were stratified according to age, sex, smoking status and pack-years of smoking, no significant association between this polymorphism and lung cancer risk was found. Moreover, the Ser326Cys genotype showed no apparent relationship with any of the histological types of lung cancer. CONCLUSION: These result suggest that the hOGG1 Ser326Cys polymorphism is not a major contributor to individual lung cancer susceptibility in Koreans.
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Humans , Codon , DNA , DNA Repair , Genome , Genotype , Lung Neoplasms , Lung , Oxygen , Smoke , SmokingABSTRACT
Purpose: Repairing damaged DNA has been shown to be involved in an increased susceptibility to cancer development and prevention. Therefore, the genetic polymorphisms of the hOGG1 gene associated with the gene repair mechanism were investigated. In this study, the possible association of genetic polymorphisms in hOGG1 with bladder tumor risk was examined. MATERIALS AND METHODS: The hospital based, case-control investigation was carried out in 168 primary bladder tumor patients and 672 controls. The DNA extracted from the blood and tissue samples was analyzed by SSCP, PCR-based restriction fragment length polymorphism (RFLP) and direct DNA sequencing in order to characterize the genetic polymorphism of hOGG1. RESULTS: Two polymorphic sites in hOGG1 were found. A polymorphism at codon 326 (1a type) in exon 7 was associated with an amino acid exchange. Another polymorphic site at codon 324 (1b type) in exon 6 was silent. The association between the polymorphism at codon 326 and the risk of the bladder tumor was examined by age-sex adjusted analysis. The distribution of the hOGG1 codon 326 genotypes in the controls (Ser/Ser, 18.9%; Ser/Cys, 54.0%; Cys/Cys, 27.1%) was significantly different from that in the bladder tumor patients (26.2%, 51.8% and 22.0%, respectively) (p=0.034, adjusted OR=0.652, 95% CI=0.44-0.97). In particular, bladder tumor risk in Korean males under 40 years old was approximately 6 times higher than in males over 40 years old (p=0.015, adjusted OR=0.165, 95% CI=0.04-0.75). Furthermore, frequent mutations of codon 326 in the hOGG1 gene in tumor tissues (23.6%) might occur during tumorigenesis. CONCLUSIONS: The data suggests that polymorphism at codon 326 of hOGG1 gene might affect tumorigenesis of a bladder tumor.
Subject(s)
Adult , Humans , Male , Carcinogenesis , Case-Control Studies , Codon , DNA , Exons , Genotype , Polymorphism, Genetic , Polymorphism, Restriction Fragment Length , Polymorphism, Single-Stranded Conformational , Sequence Analysis, DNA , Urinary Bladder Neoplasms , Urinary BladderABSTRACT
PURPOSE: 8-oxoguanine DNA glycosylase (OGG) repairs DNA by removing 8-oxoguanine (oh8Gua), a highly mutagenic oxidative DNA adduct. Recently, the human gene for OGG (hOGG1) was cloned and several genotypes have been reported. However, the implications of such genotypes in benign prostatic hyperplasia (BPH) have not been demonstrated. To assess the involvement of hOGG1 associated with the aging process on the development of BPH, we analyzed the genetic polymorphisms of hOGG1. MATERIALS AND METHODS: In 162 cases of BPH and 162 normal controls we studied the hOGG1 gene polymorphisms by performing genotype studies to characterize the genetic polymorphisms of hOGG1. RESULTS: We found a polymorphism at codon 326 in exon 7. The distribution of hOGG1 genotypes at codon 326 in BPH patients (Ser326Ser type, 18.5%; Ser326Cys type, 42.0%; and Cys326Cys type, 39.5%) was significantly different from that in the controls (14.8%, 63.0% and 22.2%, respectively) (p=0.022). Homozygosity for the Cys326Cys genotype significantly increased the risk of developing BPH, with the odds ratio (OR) being 2.286 (95% confidence interval [CI]=1.149-4.546). CONCLUSIONS: Our results suggest that the hOGG1 Cys326Cys genotype might play an important role in the development of BPH.