A Cross-Sectional Study on 3-(2-Deoxy-β-D-Erythro-Pentafuranosyl)Pyrimido[1,2-α]Purin-10(3H)-One Deoxyguanosine Adducts among Woodworkers in Tuscany, Italy

Abstract

Occupational exposure to wood dust has been estimated to affect 3.6 million workers within the European Union (EU). The most serious health effect caused by wood dust is the nasal and sinonasal cancer (SNC), which has been observed predominantly among woodworkers. Free radicals produced by inflammatory reactions as a consequence of wood dust could play a major role in SNC development. Therefore, we investigated the association between wood dust and oxidative DNA damage in the cells of nasal epithelia, the target site of SNC. We have analyzed oxidative DNA damage by determining the levels of 3-(2-deoxy-β-D-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine (M1dG), a major-peroxidation-derived DNA adduct and a biomarker of cancer risk in 136 woodworkers compared to 87 controls in Tuscany, Italy. We then examined the association of M1dG with co-exposure to volatile organic compounds (VOCs), exposure length, and urinary 15-F2t isoprostane (15-F2t-IsoP), a biomarker of oxidant status. Wood dust at the workplace was estimated by the Information System for Recording Occupational Exposures to Carcinogens. M1dG was measured using 32P-postlabeling and mass spectrometry. 15-F2t-IsoP was analyzed using ELISA. Results show a significant excess of M1dG in the woodworkers exposed to average levels of 1.48 mg/m3 relative to the controls. The overall mean ratio (MR) between the woodworkers and the controls was 1.28 (95% C.I. 1.03–1.58). After stratification for smoking habits and occupational status (exposure to wood dust alone and co-exposure to VOCs), the association of M1dG with wood dust (alone) was even greater in non-smokers workers, MR of 1.43 (95% C.I. 1.09–1.87). Conversely, not consistent results were found in ex-smokers and current smokers. M1dG was significantly associated with co-exposure to VOCs, MR of 1.95 (95% C.I. 1.46–2.61), and occupational history, MR of 2.47 (95% C.I. 1.67–3.62). Next, the frequency of M1dG was significantly correlated to the urinary excretion of 15-F2t-IsoP, regression coefficient (β) = 0.442 ± 0.172 (SE). Consistent with the hypothesis of a genotoxic mechanism, we observed an enhanced frequency of M1dG adducts in woodworkers, even at the external levels below the regulatory limit. Our data implement the understanding of SNC and could be useful for the management of the adverse effects caused by this carcinogen.