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)

Redox Biol. 2014 May 21:2:686-93. doi: 10.1016/j.redox.2014.05.003. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Adolescent
  • Cadmium / toxicity
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Child
  • DNA Damage / drug effects
  • DNA Glycosylases / genetics
  • DNA Glycosylases / metabolism
  • DNA Repair / drug effects*
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / urine
  • Environmental Exposure / analysis*
  • Environmental Monitoring
  • Female
  • Gene Expression / drug effects*
  • Humans
  • Male
  • Metallothionein / genetics
  • Metallothionein / metabolism
  • Metals, Heavy / toxicity*
  • NAD(P)H Dehydrogenase (Quinone) / genetics
  • NAD(P)H Dehydrogenase (Quinone) / metabolism
  • Oxidative Stress / drug effects*
  • RNA, Messenger / metabolism
  • Sicily
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism

Substances

  • Carrier Proteins
  • MT1A protein, human
  • Metals, Heavy
  • RNA, Messenger
  • ST13 protein, human
  • Tumor Suppressor Proteins
  • Cadmium
  • 8-Hydroxy-2'-Deoxyguanosine
  • Metallothionein
  • NAD(P)H Dehydrogenase (Quinone)
  • NQO1 protein, human
  • DNA Glycosylases
  • oxoguanine glycosylase 1, human
  • Deoxyguanosine