Low level occupational benzene exposure: changes in serum levels of oxidative stress biomarkers and of the immuno-inhibitory cytokine IL-10

Benzene has been internationally recognised as haematotoxic and carcinogen. The involvement of oxidative stress and individual genetic predisposition was explained as a major susceptibility factor for benzene toxicity in humans. Recently, benzene has been shown able to induce marked immunosuppressive effects both in animals and humans. The aim of this study is to assess modification of circulating advanced oxidation protein products (AOPPs) and glycation end products (AGEs), as early markers of oxidative stress, and of IL-10 (an immunoinhibitory cytokine) in healthy subjects chronically exposed to daily low doses of benzene, in comparison with non-exposed age-matched subjects. In our study we employed a group of oil refinery employers, working in Priolo (Enna, Sicily) (group A) and engaged in tasks increasing their occupational exposure to benzene (dock workers, employers of the load floor and working at the console); a group of office employers working in the same area (group B) was used as control.Four occupational exposure windows were taken into consideration: <1 year (subgroup A1a), <3 years (subgroup A1), 3 to < 10 years (subgroup A2), ; 10 years (subgroup A3). Also, possible correlations between benzene-induced effects and patient age (< 40 years of age or ; 40 years of age) were investigated. Benzene exposure during the entire work-shift (approximately 8 h) was measured at the breathing zone levelin all subjects,using personal diffusive samplers containing an active carbon cartridge (Radiello®). Analysis was performed using GC-FIDafter desorption of benzene from the active carbon with carbon disulfide. The 3) but significantly higher compared to controls. Serum IL-10 concentrations were measured by ELISA using a commercially available kit. Determination of serum AGEs and AOPPs was based on spectrofluorometric detection. Data (mean ± SD) were analyzed by the Mann-Whitney test. Relationship between variables was evaluated with the linear regression. Statistical significance was set at p<0.05. The data obtained showed that serum IL-10 concentrations were slightly higher in all oil refinery employers with respect to office workers (38.94±37.85 vs. 26.75±24.72 pg/ml respectively). This is in agreement with the observations that benzene has an immune suppressive action, and that IL-10 plays an essential role in fuelinduced immune suppression. This difference between benzene- exposed and non-exposed subjects became less pronounced with increasing exposure time to benzene (A1a : 48.08±66.28 pg/ml; A1 : 45.31±52.53 pg/ml, A2 : 39.66±30.89 pg/ml, A3 :27.07±15.48 pg/ml). Furthermore there is a positive relationship between IL-10 serum levels and age at employment. These data were consistent with an epidemiologic study, which highlighted the potentially greater susceptibility of older workers to benzene-induced leukaemia. Serum AOPP levels in oil refinery employers were significantly higher than those measured in controls (2.20 ± 1.42 vs. 1.57 ± 0.76 nmol/mg prot respectively). Serum AGE levels in oil refinery employees were higher (though not in a statistically significant way) than those measured in controls (603.03 ± 524.33 vs. 609.15 ± 352.27 AU/g prot respectively). There was no correlation between the serum concentrations of these two biomarkers and age and working years. Interestingly AGEs can be formed in inflamed foci both via NADPH oxidase as well as via myeloperoxidase, the same enzymes involved in benzene bioactivation. Furthermore more AGEs and AOPPs can cause induction of proinflammatory cytokines. In conclusion our data evidence that also workers exposed to low benzene concentrations may be at risk of oxidative stress damages and immunosuppression.