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

- The effects of arsenic exposure in utero and through early childhood were studied.
- Arsenic-exposed children had a reduction in arsenic methylation capacity.
- Exposed children had more DNA damage, observed as elevated salivary 8-OHdG.
- Lower salivary hOGG1 in exposed children indicated impairment of 8-OHdG repair.
- Salivary and urinary 8-OHdG levels were discordant.

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.