Occupational exposure to low levels of benzene: biomarkers of exposure, effect and susceptibility.

Abstract It is accepted that for toxicity to occur, benzene must be bioactivated to metabolites, some of which induce reactive oxygen species that can produce DNA strand breaks and other cytogenetic effects. The aim of this study was to identify useful biomarkers of exposure and effect in workers exposed to low levels of benzene, and to evaluate possible correlations between these parameters. The study consisted of petrochemical operators and non-exposed controls. Benzene exposure was measured with personal samples (Radiello®). End-shift urine samples were collected for benzene, t,t-muconic acid (t,t-MA) ans S-phenylmercapturic acid (S-PMA) measurement. Blood samples were obtained and lymphocytes were isolated for comet-DNA damage, DNA oxidation (Fpg-and Endo III-sensitive sites), DNA-repair studies and glutathione (GSH) levels. Exfoliated buccal cells, obtained by non-invasive procedure, were considered for monitoring cytogenetic damage, with micronucleus (MN) analysis. Environmental data showed low benzene exposure of petrochemical operators (9.2 ppb), but significantly higher compared to controls (p = 0.004). Among urinary metabolites, only benzene was significantly high in exposed workers (p = 0.005). Workers showed an increase of comet-DNA oxidation (Fpg) and significant decrease of DNA-repair capacity (-35%) compared to controls. Lymphocyte GSH was significant decreased in exposed (p = 0.036). DNA damage and DNA-base oxidation were significantly correlated with years- and benzene-exposure. A trend of negative correlations were between GSH and DNA damage or DNA-base oxidation (Fpg and Endo III). Exfoliated buccal cells showed significant increase in MN frequency in workers compared to controls (p = 0.0026). The genotoxic effects induced by benzene at low-level of exposure can be detected with suitable and sensitive biomarkers as the standard and modified comet and the MN assay. Additionally, the buccal cells result to be sensitive targets and useful to study early genotoxic effects in workers exposed to inhaled chemical substances, also at low doses.