title: 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).
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.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Pizzino
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bitto
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Interdonato
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Galfo
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: Natasha
authors.initials: N
authors.lastname: Irrera
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Mecchio
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pallio
authors.affiliation: Department of Paediatric, Gynaecological, Microbiological and Biomedical Sciences, University of Messina, Messina, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Ramistella
authors.affiliation: Department of Paediatric, Gynaecological, Microbiological and Biomedical Sciences, University of Messina, Messina, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: De Luca
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: Letteria
authors.initials: L
authors.lastname: Minutoli
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Squadrito
authors.affiliation: Department of Paediatric, Gynaecological, Microbiological and Biomedical Sciences, University of Messina, Messina, Italy.
authors.forename: Domenica
authors.initials: D
authors.lastname: Altavilla
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000293:Adolescent; D002104:Cadmium / Q000633:toxicity; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002648:Child; D004249:DNA Damage / Q000187:drug effects; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D004781:Environmental Exposure / Q000032:analysis*; D004784:Environmental Monitoring; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008297:Male; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D019216:Metals, Heavy / Q000633:toxicity*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D012802:Sicily; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones
chemical_list: D000080242:8-Hydroxy-2'-Deoxyguanosine; D002104:Cadmium; D002352:Carrier Proteins; D045647:DNA Glycosylases; D003849:Deoxyguanosine; D008668:Metallothionein; D019216:Metals, Heavy; D016660:NAD(P)H Dehydrogenase (Quinone); D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C530099:MT1A protein, human; C101119:ST13 protein, human; D018832:Molecular Chaperones; C447479:NQO1 protein, human; C479058:oxoguanine glycosylase 1, human