Oxidative DNA damage and repair in children exposed to low levels of arsenic in utero and during early childhood: application of salivary and urinary biomarkers

Toxicol Appl Pharmacol. 2013 Dec 15;273(3):569-79. doi: 10.1016/j.taap.2013.10.002. Epub 2013 Oct 12.

Abstract

The present study aimed to assess arsenic exposure and its effect on oxidative DNA damage and repair in young children exposed in utero and continued to live in arsenic-contaminated areas. To address the need for biological specimens that can be acquired with minimal discomfort to children, we used non-invasive urinary and salivary-based assays for assessing arsenic exposure and early biological effects that have potentially serious health implications. Levels of arsenic in nails showed the greatest magnitude of difference between exposed and control groups, followed by arsenic concentrations in saliva and urine. Arsenic levels in saliva showed significant positive correlations with other biomarkers of arsenic exposure, including arsenic accumulation in nails (r=0.56, P<0.001) and arsenic concentration in urine (r=0.50, P<0.05). Exposed children had a significant reduction in arsenic methylation capacity indicated by decreased primary methylation index and secondary methylation index in both urine and saliva samples. Levels of salivary 8-OHdG in exposed children were significantly higher (~4-fold, P<0.01), whereas levels of urinary 8-OHdG excretion and salivary hOGG1 expression were significantly lower in exposed children (~3-fold, P<0.05), suggesting a defect in hOGG1 that resulted in ineffective cleavage of 8-OHdG. Multiple regression analysis results showed that levels of inorganic arsenic (iAs) in saliva and urine had a significant positive association with salivary 8-OHdG and a significant negative association with salivary hOGG1 expression.

Keywords: Arsenic; Children; DNA repair; Oxidative DNA damage; Saliva; Urine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Arsenic / toxicity*
  • Arsenic / urine*
  • Biomarkers / urine
  • Child
  • Child, Preschool
  • DNA Damage / drug effects*
  • DNA Glycosylases / genetics
  • DNA Glycosylases / metabolism
  • DNA Repair / drug effects*
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / metabolism
  • Deoxyguanosine / urine
  • Drinking Water / chemistry
  • Environmental Exposure
  • Female
  • Humans
  • Male
  • Nails / chemistry
  • Oxidative Stress / drug effects*
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Saliva / chemistry
  • Surveys and Questionnaires

Substances

  • Biomarkers
  • Drinking Water
  • 8-Hydroxy-2'-Deoxyguanosine
  • DNA Glycosylases
  • oxoguanine glycosylase 1, human
  • Deoxyguanosine
  • Arsenic