Frontiers in Genetics (Jun 2015)
Exposure to arsenic in relation with DNA damage in adolescents of the 3rd Flemish environment and health study (2012-2014)
Abstract
Arsenic (As) is a compound naturally present in the environment. Recent studies have shown detectable levels of As in rice, rice food products, and apple juice. As is a well known carcinogen and is related to multiple health effects, for example dermal and kidney toxicity. Recent epidemiological studies have shown that As exposure is also a risk factor for cardiovascular diseases. We evaluated the exposure to As in a sample of 408 adolescents that were recruited from the general population in Flanders as part of the third Flemish Environment and Health Study (FLEHS3). We tested whether the current levels of As exposure were associated with oxidative stress biomarkers or biomarkers for DNA damage. In this study, the individual exposure to As was estimated by measuring total As in whole blood and different toxic As metabolites in urine: As III, As V, mono-methylarsonous acid (MMA), dimethylarsinous acid (DMA), and the non-toxic, organic compound arsenobetaine. The sum of the toxic compounds was defined as toxic relevant As (TRA). DNA damage was measured using the alkaline comet assay and the micronucleus test in whole blood samples, and by an enzyme-linked immunosorbent assay (ELISA, Gentaur) quantifying 8-hydroxy-2-deoxyguanosine (8-OHdG) in urine. Multiple linear regression models were used to estimate the change of effect for an increase of the exposure from P25 to P75 (P25-P75). All models were adjusted for gender, age, smoking status and statistically significant (p<0.05) covariates. The exposure biomarker As III was categorised due to the large number values below the quantification limit (LOQ). The effect estimate was given for the group with the highest As III exposure versus the group with values below LOQ. Multiple regression analysis showed significant positive associations of urinary inorganic As III (iAsIII) and MMA with DNA breaks measured by the comet assay (iAsIII: β=0.333, 95% CI=0.061-0.605; MMA: β=0.090, 95% CI=0.014-0.166). Urinary iAs levels were positively associated with concentrations of 8-OHdG (iAsIII: OR=1.231, 95% CI=1.107-1.369; iAsV: OR=1.074, 95% CI=1.014-1.137; MMA: OR=1.154, 95% CI=1.105-1.205; DMA: OR=1.099, 95% CI: 1.041-1.160; TRA: OR=1.131, 95% CI= 1.073-1.192). No statistically significant associations were found with the micronucleus test. Although 82% of the adolescents had a TRA concentration below the Biomonitoring Equivalents for non-carcinogenic effects (≤6.4 µg/l), the data obtained in this study indicate that chronic exposure of Flemish adolescents to very low levels of As, compared to studies in e.g. Bangladesh, and both in whole blood (total As) or urine (TRA), is associated with oxidative stress and DNA damage. The studies of the Flemish Center of Expertise on Environment and Health were commissioned, financed and steered by the Ministry of the Flemish Community (Department of Economics, Science and Innovation; Flemish Agency for Care and Health; and Department of Environment, Nature and Energy).
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