Abstract 3450: Changes in mitochondrial DNA copy number in subjects exposed to low-dose benzene

Abstract

Abstract BACKGROUND: Benzene is a recognized hematotoxic and leukemogenic agent at high exposures, but whether low benzene levels found nowadays in the environment and selected occupational settings cause any hematotoxicity is unresolved. Exposure to benzene at very high doses has been recently shown to increase mitochondrial DNA copy number (mtDNAcn), as a mechanism to compensate for damaged mitochondria. OBJECTIVES: To evaluate whether low-dose benzene exposure was related with mtDNAcn in blood from 527 subjects from three Italian cities. METHODS: We measured mtDNAcn in blood leukocytes from 366 subjects exposed to benzene in working environments (petrochemical workers, airport refuelling workers, bus drivers, gas station attendants and traffic police officers) and 161 referent office workers in Milan, Cagliari, and Genoa. Individual exposure to benzene was determined by means of a Chromosorb 106 passive sampler, worn by the study subjects near the breathing zone during the work shift. Benzene concentrations were 53.3 μg/m3 (95% CI: 42.1 - 64.5 μg/m3) in the exposed subjects and 11.4 μg/m3 (95% CI: 8.4 - 14.4 μg/m3) in the referents. Benzene levels were almost twice as high in Milan and Cagliari (mean = 51.9 μg/m3 and 51.6 μg/m3, respectively) as in Genoa (mean = 20.5 μg/m3). Relative mtDNAcn was measured by a quantitative real-time PCR assay determining the ratio of mtDNAcn to single copy nuclear gene (human beta-globin) copy number in experimental samples. Statistical analyses included univariate analysis with non-parametric tests for differences among exposure categories and multivariate linear regression analyses, adjusting for main confounders of interest (sex, age, city of origin, educational level, smoking habit, alcohol consumption). RESULTS: mtDNAcn increased in association with increasing exposures due to different occupations. In Cagliari, mtDNAcn was 1.88 in petrochemical workers (highest exposure), 1.80 in airport refuelling workers (intermediate exposure), 1.71 in subjects living near a petrochemical plant (low exposure), and 1.21 in referent subjects (p-trend = 0.0001). In Genoa, mtDNAcn was 0.98 in bus drivers (exposed group), and 0.83 in referent subjects (p-trend = 0.0121). In Milan, mtDNAcn was 0.92 in gas station attendants (high exposure), 1.19 in traffic police officers (intermediate exposure), and 0.82 in referent subjects (p-trend = 0.0001). In the entire study population, personal airborne benzene levels were positively associated with mtDNAcn (β = 0.055, 95% CI: 0.015 - 0.096; p = 0.008). CONCLUSIONS: Benzene exposure may induce mtDNA amplification at low-doses, a potential response to oxidative stress caused by benzene-induced production of reactive oxygen species. Our results indicate potential toxicity of low-level benzene exposures due to mitochondrial dysfunction. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3450.