title: Metabolic polymorphisms and biomarkers of effect in the biomonitoring of occupational exposure to low-levels of benzene: state of the art.
abstract: Current levels of occupational exposure to benzene, a genotoxic human carcinogen, in Western countries are reduced by two-three orders of magnitude (from ppm to ppb) as compared to the past. However, as benzene toxicity is strongly dependent on biotransformation and recent evidence underlines a higher efficiency of bio-activation pathways at lower levels of exposure, toxic effects at low doses could be higher than expected, particularly in susceptible individuals. Currently, biological monitoring can allow accurate exposure assessment, relying on sensitive and specific enough biomarkers of internal dose. The availability of similarly reliable biomarkers of early effect or susceptibility could greatly improve the risk assessment process to such an extent that risk could even be assessed at the individual level. As to susceptibility biomarkers, functional genetic polymorphisms of relevant biotransformation enzymes may modulate the risk of adverse effects (NQO1) and the levels of biomarkers of internal dose, in particular S-phenylmercapturic acid (GSTM1, GSTT1, GSTA1). Among biomarkers of early effect, genotoxicity indicators, although sensitive in some cases, are too aspecific for routine use in occupational health surveillance programmes. Currently only the periodical blood cell count seems suitable enough to be applied in the longitudinal monitoring of effects from benzene exposure. Novel biomarkers of early effect are expected from higher collaboration among toxicologists and clinicians, also using advanced "omics" techniques.
authors.affiliation: Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, Section of Public Health and Human Sciences, University of Brescia, Piazzale Spedali Civili 1, 25123 Brescia, Italy. Electronic address: depalma@med.unibs.it.
authors.forename: G
authors.initials: G
authors.lastname: De Palma
authors.affiliation: Department of Public Health, Section of Occupational Medicine and Toxicology, University of Napoli Federico II, Via S. Pansini, 5, 80131 Napoli, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Manno
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000652:urine; D001554:Benzene / Q000737:chemistry / Q000633:toxicity*; D015415:Biomarkers; D004784:Environmental Monitoring / Q000379:methods*; D004785:Environmental Pollutants / Q000737:chemistry / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000502:physiology; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism / Q000652:urine; D006801:Humans; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D016273:Occupational Exposure / Q000032:analysis*; D011110:Polymorphism, Genetic / Q000502:physiology*; D059467:Transcriptome
chemical_list: D015415:Biomarkers; D004785:Environmental Pollutants; C053003:S-phenyl-N-acetylcysteine; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D005982:Glutathione Transferase; D001554:Benzene; D000111:Acetylcysteine
keywords: Benzene; Biological monitoring; Genetic polymorphism; Genotoxicity