1. 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).
- Author
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Pizzino G, Bitto A, Interdonato M, Galfo F, Irrera N, Mecchio A, Pallio G, Ramistella V, De Luca F, Minutoli L, Squadrito F, and Altavilla D
- Subjects
- 8-Hydroxy-2'-Deoxyguanosine, Adolescent, Cadmium toxicity, Carrier Proteins genetics, Carrier Proteins metabolism, Child, DNA Damage drug effects, DNA Glycosylases genetics, DNA Glycosylases metabolism, Deoxyguanosine analogs & derivatives, Deoxyguanosine urine, Environmental Monitoring, Female, Humans, Male, Metallothionein genetics, Metallothionein metabolism, NAD(P)H Dehydrogenase (Quinone) genetics, NAD(P)H Dehydrogenase (Quinone) metabolism, RNA, Messenger metabolism, Sicily, Tumor Suppressor Proteins genetics, Tumor Suppressor Proteins metabolism, DNA Repair drug effects, Environmental Exposure analysis, Gene Expression drug effects, Metals, Heavy toxicity, Oxidative Stress drug effects
- 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 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 µg/L; 25th-75th percentile: 0.3-0.56] than in control adolescents [geometric mean, 0.26 µg/L; 25th-75th percentile: 0.2-0.3]. Chromium was also significantly elevated in exposed [geometric mean, 1.52 µg/L; 25th-75th percentile: 1.19-1.93] compared with controls [geometric mean, 1.25 µg/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 µg/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.
- Published
- 2014
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