Oxidatively damaged DNA in the nasal epithelium of workers occupationally exposed to silica dust in Tuscany region, Italy

Chronic silica exposure has been associated to cancer and silicosis. Furthermore, the induction of oxidative stress and the generation of reactive oxygen species have been indicated to play a main role in the carcinogenicity of respirable silica. Therefore, we conducted a cross-sectional study to evaluate the prevalence of 3-(2-deoxy-beta-D-erythro-pentafuranosyl) pyrimido[1,2-alpha]purin-10(3H)-one deoxyguanosine (M(1)dG) adducts, a biomarker of oxidative stress and peroxidation of lipids, in the nasal epithelium of 135 silica-exposed workers, employed in pottery, ceramic and marble manufacturing plants as well as in a stone quarry, in respect to 118 controls living in Tuscany region, Italy. The M(1)dG generation was measured by the P-32-postlabelling assay. Significant higher levels of M(1)dG adducts per 10(8) normal nucleotides were observed in the nasal epithelium of smokers, 77.9 +/- 9.8 (SE), and in those of former smokers, 80.7 +/- 9.7 (SE), as compared to non-smokers, 57.1 +/- 6.2 (SE), P = 0.001 and P = 0.004, respectively. Significant increments of M(1)dG adducts were found in the nasal epithelium of workers that handle artificial marble conglomerates, 184 +/- 36.4 (SE), and in those of quarry workers, 120 +/- 34.7 (SE), with respect to controls, 50.6 +/- 2.7 (SE), P = 0.014 and P < 0.001, respectively. Null increments were observed in association with the pottery and the ceramic factories. After stratification for different exposures, silica-exposed workers that were co-exposed to organic solvents, and welding and exhaust fumes have significantly higher M(1)dG levels, 90.4 +/- 13.4 (SE), P = 0.014 vs. control. Our data suggested that silica exposure might be associated with genotoxicity in the nasal epithelial cells of silica-exposed workers that handle of artificial marble conglomerates and quarry workers. Importantly, we observed that co-exposures to other respiratory carcinogens may have contributed to enhance the burden of M(1)dG adducts in the nasal epithelium of silica-exposed workers.