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1.
Int J Occup Environ Med ; 10(3): 124-136, 2019 07.
Article in English | MEDLINE | ID: mdl-31325295

ABSTRACT

BACKGROUND: Coke oven workers are exposed to polycyclic aromatic hydrocarbons (PAHs) with possible genotoxicity and carcinogenicity. Metabolizing enzymes genes and DNA repair genes are suspected to be correlated with the level of DNA damage. They may contribute to variable individual sensitivity to DNA damage induced by PAHs exposure at workplace. OBJECTIVE: To investigate the relationship between biomarkers of PAHs: 1-hydroxypyrene (1-OHP), DNA adducts, and 8-hydroxy-2-deoxyguanosine (8-OHdG) in coke oven workers, and to assess the role of cytochrome P2E1 (CYP2E1) gene expression and DNA repairing gene (XRCC1) polymorphism in detecting workers at risk. METHODS: 85 exposed workers and 85 unexposed controls were enrolled into this study. Urinary 1-OHP, 8-OHdG, and BPDE-DNA adduct were measured. CYP2E1 gene expression and genotyping of XRCC1 399 Arg/Gln were evaluated by real-time PCR. RESULTS: The median urinary 1-OHP levels (6.3 µmol/mol creatinine), urinary 8-OHdG (7.9 ng/mg creatinine), DNA adducts (6.7 ng/µg DNA) in the exposed group were significantly higher than those in the unexposed group. Carriers of the variant allele (Gln) of XRCC1 had the highest levels of 1-OHP, DNA adducts and 8-OHdG, and the lowest level of CYP2E1 gene expression. In exposed workers, significant positive correlations were found between 1-OHP level and each of the work duration, 8-OHdG, and DNA adducts levels. There was a significant negative correlation between 1-OHP level and CYP2E1 gene expression. Work duration and CYP2E1 gene expression were predictors of DNA adducts level; 1-OHP level and work duration were predictors of urinary 8-OHdG level. CONCLUSION: Workers with higher exposure to PAH were more prone to oxidative DNA damage and cancer development. DNA adducts level reflects the balance between their production by CYP2E1 and elimination by XRCC1 gene.


Subject(s)
Cytochrome P-450 CYP2E1/genetics , DNA Adducts/genetics , Deoxyguanosine/analogs & derivatives , Environmental Monitoring/methods , Occupational Exposure/analysis , Pyrenes/urine , X-ray Repair Cross Complementing Protein 1/genetics , 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide , 8-Hydroxy-2'-Deoxyguanosine , Adult , Biomarkers/urine , Coke , Cytochrome P-450 CYP2E1/biosynthesis , DNA Adducts/urine , DNA Damage/drug effects , DNA Repair/genetics , Deoxyguanosine/urine , Egypt , Humans , Male , Middle Aged , Polycyclic Aromatic Hydrocarbons/urine , Polymorphism, Genetic , Risk Assessment , X-ray Repair Cross Complementing Protein 1/biosynthesis , Young Adult
2.
Urology ; 108: 108-113, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28755962

ABSTRACT

OBJECTIVE: To evaluate the association between miRNAs and veno-occlusive erectile dysfunction. Recently, this association between miRNAs and erectile dysfunction was extensively studied using animal models. Our aim was to explore the miRNAs expressions and functions in the development of erectile dysfunction, especially veno-occlusive dysfunction, using a human tissue. PATIENTS AND METHODS: We prospectively recruited 60 patients with erectile dysfunction and controls between July 2015 and July 2016. The 30 patients had refractory veno-occlusive erectile dysfunction that was proven by investigations. They were scheduled for penile implant. The 30 controls were scheduled for repair of their fracture. We measured miRNAs (200a and 206) and nitric oxide in cavernous tissue and serum of both patients with erectile dysfunction and controls. RESULTS: A significant association was found between the 2 mentioned miRNAs and erectile dysfunction (P <.001). Mean level of nitric oxide in cavernous tissue of the controls was significantly higher than that in the patients (P <.001). miRNA 200a showed a cutoff value of 1.135 with 95% sensitivity and 100% specificity, whereas miRNA 206 showed a cutoff value of 1.125 with 100% sensitivity and 100% specificity. CONCLUSION: To the best of our knowledge, our study is the first report to measure the level of miRNAs in the cavernous tissue, using a human tissue. Furthermore, this study can be considered a good step of deploying miRNAs through a blood test to detect early negative changes that lead to erectile dysfunction. Finally, we recommend more studies to be conducted to better understand if these miRNAs are involved in the pathophysiology of veno-occlusive erectile dysfunction.


Subject(s)
Gene Expression Regulation , Impotence, Vasculogenic/genetics , MicroRNAs/genetics , Penile Erection/physiology , Penis/metabolism , RNA/genetics , Adult , Biomarkers/metabolism , Follow-Up Studies , Humans , Impotence, Vasculogenic/metabolism , Impotence, Vasculogenic/physiopathology , Male , MicroRNAs/biosynthesis , Middle Aged , Nitric Oxide/metabolism , Penis/diagnostic imaging , RNA/metabolism , ROC Curve , Real-Time Polymerase Chain Reaction , Retrospective Studies , Ultrasonography, Doppler
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