Document Detail


Occupational exposure to low levels of benzene: Biomarkers of exposure and nucleic acid oxidation and their modulation by polymorphic xenobiotic metabolizing enzymes.
MedLine Citation:
PMID:  20100551     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This study investigated nucleic acid oxidation associated with exposure to benzene at low levels in 239 workers recruited among traffic policemen, taxi drivers and gasoline pump attendants of the city of Parma (Italy). Biomarkers of exposure, namely urinary t,t-muconic acid (t,t-MA) and S-phenylmercapturic acid (S-PMA), urinary cotinine, and urinary biomarkers of nucleic acid oxidation, namely 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydroguanine (8-oxoGua) were determined by liquid chromatography-tandem mass spectrometry. Relevant polymorphisms of NAD(P)H:quinone oxidoreductase (NQO1), glutathione S-transferases M1-1 (GSTM1), T1-1 (GSTT1), and A1 (GSTA1) were characterized by polymerase chain reaction-based methods in a subgroup of subjects. Biomarkers of nucleic acid oxidation were correlated with each other (r> or =0.32, p<0.0001) and with exposure biomarkers (r> or =0.28, p<0.0001). Multiple linear regression models including age, sex and smoking habits as independent variables demonstrated that benzene exposure is associated with oxidation damage to nucleic acid, particularly to RNA (p<0.0001) and is modulated by the NQO1 polymorphism. The study confirmed a significant modulating effect of GSTM1 (p=0.010), GSTT1 (p=0.023) and GSTA1 (p=0.048) polymorphisms on S-PMA excretion, with a significant interaction between GSTM1 and both GSTT1 and GSTA1 (p=0.006 and p=0.037, respectively).
Authors:
Paola Manini; Giuseppe De Palma; Roberta Andreoli; Paola Mozzoni; Diana Poli; Matteo Goldoni; Marta Petyx; Pietro Apostoli; Antonio Mutti
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-01-25
Journal Detail:
Title:  Toxicology letters     Volume:  193     ISSN:  1879-3169     ISO Abbreviation:  Toxicol. Lett.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-11     Completed Date:  2010-03-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7709027     Medline TA:  Toxicol Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  229-35     Citation Subset:  IM    
Copyright Information:
2010 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
Department of Clinical Medicine, Nephrology and Health Sciences, University of Parma, Italy. paola.manini@unipr.it
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MeSH Terms
Descriptor/Qualifier:
Acetylcysteine / analogs & derivatives,  urine
Adult
Benzene / toxicity*
Biological Markers
Female
Glutathione Transferase / genetics
Humans
Male
Middle Aged
NAD(P)H Dehydrogenase (Quinone) / genetics
Nucleic Acids / metabolism*
Occupational Exposure / adverse effects*
Oxidation-Reduction
Polymorphism, Genetic*
Regression Analysis
Sorbic Acid / analogs & derivatives,  metabolism
Xenobiotics / metabolism*
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Nucleic Acids; 0/Xenobiotics; 110-44-1/Sorbic Acid; 4775-80-8/S-phenyl-N-acetylcysteine; 505-70-4/muconic acid; 616-91-1/Acetylcysteine; 71-43-2/Benzene; EC 1.6.5.2/NAD(P)H Dehydrogenase (Quinone); EC 1.6.99.2/NQO1 protein, human; EC 2.5.1.18/Glutathione Transferase; EC 2.5.1.18/glutathione S-transferase M1

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