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 45km 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, 0.46μg/L; 25th-75th percentile: 0.3-0.56] than in control adolescents [geometric mean, 0.26μg/L; 25th-75th percentile: 0.2-0.3]. Chromium was also significantly elevated in exposed [geometric mean, 1.52μg/L; 25th-75th percentile: 1.19-1.93] compared with controls [geometric mean, 1.25μg/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 61.87μg/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 over-expressed 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. © 2014 The Authors.
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).
PIZZINO, CARMELO GABRIELE;BITTO, ALESSANDRA;INTERDONATO, Monica;GALFO, FEDERICA;IRRERA, NATASHA;PALLIO, GIOVANNI;DE LUCA, Filippo;MINUTOLI, Letteria;SQUADRITO, Francesco;ALTAVILLA, Domenica
2014-01-01
Abstract
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 45km 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, 0.46μg/L; 25th-75th percentile: 0.3-0.56] than in control adolescents [geometric mean, 0.26μg/L; 25th-75th percentile: 0.2-0.3]. Chromium was also significantly elevated in exposed [geometric mean, 1.52μg/L; 25th-75th percentile: 1.19-1.93] compared with controls [geometric mean, 1.25μg/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 61.87μg/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 over-expressed 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. © 2014 The Authors.Pubblicazioni consigliate
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