title: Influence of genetic polymorphism on t,t-MA/S-PMA ratio in 301 benzene exposed subjects.
abstract: This study investigated the effect of polymorphic genes GSTT1, GSTM1, GSTA1, EHPX1, NQO1, CYP2E1, CYP1A and MPO on the urinary concentrations and ratio (R) of the benzene metabolites trans,trans-muconic acid (t,t-MA) and S-phenyl mercapturic acid (S-PMA) in 301 oil refinery workers. The metabolites' concentrations are lower and R is higher (100.66) in non-smokers (n=184) than in smokers (n=117, R=36.54). Non-smokers have lower S-PMA and a higher R in GSTT1 null genotypes than in positive, and a higher S-PMA and a lower R in GSTA1 wild type genotypes. In smokers the GSTT1 null genotype effect on both S-PMA and R is confirmed, and is also shown in GSTM1 null, but not in GSTA1 wild type genotypes. GSTT1 null polymorphism reduces the conjugation rate of benzene epoxide with GSH, and to a lesser extent also GSTTA1 mutant, GSTM1 null and NQO1 mutant genotypes. The activity of one GST is compensated by another in GSTM1 and GSTA1 defective subjects, but not in GSTT1 null genotypes, whose average S-PMA excretion is about 50% with respect to the positive ones, for the same benzene exposure. R showed to be a more sensitive marker for these effects than the metabolite levels.
authors: INAIL Research, Department of Occupational Hygiene, Via di Fontana Candida 1, 00040 Monteporzio Catone, Rome, Italy. Electronic address: d.carbonari@inail.it.
authors: Damiano
authors: D
authors: Carbonari
authors: INAIL Research, Department of Occupational Hygiene, Via di Fontana Candida 1, 00040 Monteporzio Catone, Rome, Italy.
authors: Annarita
authors: A
authors: Proietto
authors: INAIL Research, Department of Occupational Hygiene, Via di Fontana Candida 1, 00040 Monteporzio Catone, Rome, Italy.
authors: Marzia
authors: M
authors: Fioretti
authors: INAIL Research, Department of Occupational Medicine, Via di Fontana Candida 1, 00040 Monteporzio Catone, Rome, Italy. Electronic address: g.tranfo@inail.it.
authors: Giovanna
authors: G
authors: Tranfo
authors: INAIL Research, Department of Occupational Medicine, Via di Fontana Candida 1, 00040 Monteporzio Catone, Rome, Italy.
authors: Enrico
authors: E
authors: Paci
authors: INAIL Research, Department for Production Plants and Interactions with the Environment, Via di Fontana Candida 1, 00040 Monteporzio Catone, Rome, Italy. Electronic address: m.papacchini@inail.it.
authors: Maddalena
authors: M
authors: Papacchini
authors: INAIL Research, Department of Occupational Hygiene, Via di Fontana Candida 1, 00040 Monteporzio Catone, Rome, Italy. Electronic address: a.mansi@inail.it.
authors: Antonella
authors: A
authors: Mansi
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D000328:Adult; D001554:Benzene / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D007221:Industry; D008297:Male; D016273:Occupational Exposure; D010578:Petroleum; D011110:Polymorphism, Genetic; D012907:Smoking / Q000009:adverse effects*; D013011:Sorbic Acid / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D010578:Petroleum; C005939:muconic acid; C053003:S-phenyl-N-acetylcysteine; D001554:Benzene; D000111:Acetylcysteine; D013011:Sorbic Acid
keywords: Benzene exposure; Genetic polymorphism; Risk assessment; Smoking; t,t-MA/S-PMA ratio