Oxidative stress and DNA repair and detoxification gene expression in adolescents exposed to heavy metals living in the Milazzo-Valle del Mela area (Sicily, Italy)

Background: The area of Milazzo-Valle del Mela (Sicily, Italy) is considered at high risk of environmental crisis by regional authorities. Objective: To measure oxidative-stress, DNA repair and detoxification genes in school children living near the industrial area and in age-matched controls. Methods: The parent study was a biomonitoring investigation evaluating heavy metal urine levels in 226 children aged 12-14 years, living in the high risk area, and in 29 age-matched controls living 45 km far from the industrial site. In the present study 67 exposed adolescents and 29 controls were included. Samples were analyzed for urinary 8-hydroxydeoxyguanosine (8OHdG) levels, and gene expression of OGG1 (DNA repair gene), NQO1, ST13, and MT1A (detoxifying genes). Results: Urinary cadmium was higher (p = 0.0004) in exposed [geometric mean, 0.46 mu g/L; 25th-75th percentile: 0.3-0.56] than in control adolescents [geometric mean, 0.26 mu g/L; 25th-75th percentile: 0.2-0.3]. Chromium was also significantly elevated in exposed [geometric mean, 1.52 mu g/L; 25th-75th percentile: 1.19-1.93] compared with controls [geometric mean, 1.25 mu g/L; 25th-75th percentile: 1.05-1.48; p = 0.02]. Urinary 8-OHdG concentration was greater in exposed than in controls (71.49 vs 61.87 mu g/L, p = 0.02), and it was correlated with cadmium levels (r = 0.46, p < 0.0001), and with the combined exposure index (r = 0.43, p < 0.0001). Moreover, cadmium levels showed a robust correlation with OGG1 and MT1A gene expression levels (r = 0.44, p < 0.0001; r = 0.39, p < 0.0001, respectively). Finally, OGG1 and MT1A were overexpressed in adolescents from Milazzo-Valle del Mela area compared with controls (p = 0.0004; p < 0.0001, respectively). Conclusions: Continuous exposure at relatively low concentrations of heavy metals is associated with increased oxidative DNA damage and impaired expression of DNA repair and detoxification genes in adolescents. (C) 2014 The Authors. Published by Elsevier B.V.