Associations of Arsenic Exposure With Telomere Length and Naïve T Cells in Childhood-A Birth Cohort Study

Abstract

There is limited knowledge of association between arsenic exposure and telomere length (TL) and signal joint T-cell receptor excision circle (sjTREC) that are potential biomarkers of immune senescence and disease susceptibility. We aimed to clarify whether long-term inorganic arsenic exposure influences TL and sjTRECs in childhood. Children born in a longitudinal mother-child cohort were followed-up at 4.5 (n = 275) and 9 years (n = 351) of age. Arsenic exposure was assessed by metabolite concentrations in urine (U-As) from mothers at gestational week 8 (prenatal) and their children at 4.5 and 9 years. TL and sjTRECs were determined in blood cells using quantitative PCR. The oxidative DNA damage marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) in plasma was measured by ELISA. In multivariable-adjusted spline regression analyses, both prenatal and childhood arsenic exposure above U-As of 45 µg/l were significantly inversely associated with TL and sjTRECs at 9 years. Fraction of monomethylarsonic acid (MMA) above spline knot 7% were significantly inversely associated with both TL and sjTRECs reflecting increased toxicity due to less-efficient arsenic metabolism in 9--year-old children. Prenatal and childhood arsenic exposure were positively associated with 8-OHdG at 9 years which in turn was inversely associated with sjTRECs at 9 years. However, adjustment with 8-OHdG did not change the estimates of the association of U-As with sjTRECs reflecting little contribution from 8-OHdG-induced oxidative stress. Our findings suggest that chronic arsenic exposure from early life can result in TL attrition and lower production of naïve T cells potentially leading to immunosenescence and immunodeficiency.