Associations of Arsenic Exposure With Telomere Length and Naïve T Cells in Childhood—A Birth Cohort Study. (10th May 2018)

• Record Type: Journal Article
• Authors: Mannan, Tania; Ahmed, Sultan; Akhtar, Evana; Ahsan, Khalid Bin; Haq, Ahsanul; Kippler, Maria; Vahter, Marie; Raqib, Rubhana
• Is Part Of: Toxicological sciences. Volume 164:Number 2(2018)
• Page Start: 539
• Page End: 549
• Publication Date: 2018-05-10
• Subjects: telomere length -- immunosenescence -- sjTRECs -- arsenic -- birth cohort -- school children; Toxicology -- Periodicals; Toxicology -- Periodicals; Toxicology; Periodicals; 615.9
• DOI: 10.1093/toxsci/kfy105
• Languages: English
• ISSNs: 1096-6080

Abstract

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-2ʹ-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.