title: Occupational exposure to low levels of benzene: Biomarkers of exposure and nucleic acid oxidation and their modulation by polymorphic xenobiotic metabolizing enzymes.
abstract: 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.affiliation: Department of Clinical Medicine, Nephrology and Health Sciences, University of Parma, Italy. paola.manini@unipr.it
authors.forename: Paola
authors.initials: P
authors.lastname: Manini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Palma
authors.forename: Roberta
authors.initials: R
authors.lastname: Andreoli
authors.forename: Paola
authors.initials: P
authors.lastname: Mozzoni
authors.forename: Diana
authors.initials: D
authors.lastname: Poli
authors.forename: Matteo
authors.initials: M
authors.lastname: Goldoni
authors.forename: Marta
authors.initials: M
authors.lastname: Petyx
authors.forename: Pietro
authors.initials: P
authors.lastname: Apostoli
authors.forename: Antonio
authors.initials: A
authors.lastname: Mutti
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000652:urine; D000328:Adult; D001554:Benzene / Q000633:toxicity*; D015415:Biomarkers; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics; D009696:Nucleic Acids / Q000378:metabolism*; D016273:Occupational Exposure / Q000009:adverse effects*; D010084:Oxidation-Reduction; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D013011:Sorbic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D015262:Xenobiotics / Q000378:metabolism*
chemical_list: D000111:Acetylcysteine; D001554:Benzene; D015415:Biomarkers; D005982:Glutathione Transferase; D016660:NAD(P)H Dehydrogenase (Quinone); D009696:Nucleic Acids; D013011:Sorbic Acid; D015262:Xenobiotics; C005939:muconic acid; C053003:S-phenyl-N-acetylcysteine; C447479:NQO1 protein, human