Prenatal Arsenic Exposure and DNA Methylation in Maternal and Umbilical Cord Blood Leukocytes

Background: Arsenic is an epigenetic toxicant and could influence fetal developmental programming. Objectives: We evaluated the association between arsenic exposure and DNA methylation in maternal and umbilical cord leukocytes. Methods: Drinking-water and urine samples were collected when women were at ≤ 28 weeks gestation; the samples were analyzed for arsenic using inductively coupled plasma mass spectrometry. DNA methylation at CpG sites in p16 (n = 7) and p53 (n = 4), and in LINE-1 and Alu repetitive elements (3 CpG sites in each), was quantified using pyrosequencing in 113 pairs of maternal and umbilical blood samples. We used general linear models to evaluate the relationship between DNA methylation and tertiles of arsenic exposure. Results: Mean (± SD) drinking-water arsenic concentration was 14.8 ± 36.2 μg/L (range: < 1–230 μg/L). Methylation in LINE-1 increased by 1.36% [95% confidence interval (CI): 0.52, 2.21%] and 1.08% (95% CI: 0.07, 2.10%) in umbilical cord and maternal leukocytes, respectively, in association with the highest versus lowest tertile of total urinary arsenic per gram creatinine. Arsenic exposure was also associated with higher methylation of some of the tested CpG sites in the promoter region of p16 in umbilical cord and maternal leukocytes. No associations were observed for Alu or p53 methylation. Conclusions: Exposure to higher levels of arsenic was positively associated with DNA methylation in LINE-1 repeated elements, and to a lesser degree at CpG sites within the promoter region of the tumor suppressor gene :p16. Associations were observed in both maternal and fetal leukocytes. Future research is needed to confirm these results and determine if these small increases in methylation are associated with any health effects

Variability in Biomarkers of Arsenic Exposure and Metabolism in Adults over Time

Background: Urinary arsenic metabolites (UAs) are used as biomarkers of exposure and metabolism. Ojectives: To characterize inter- and intraindividual variability in UAs in healthy individuals. Methods: In a longitudinal study conducted in Bangladesh, we collected water and spot urine samples from 196 participants every 3 months for 2 years. Water arsenic (As) was measured by inductively coupled plasma-mass spectrometry and urinary As [arsenite, arsenate, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)] were detected using high-performance liquid chromatography-hydride-generated atomic absorption spectrometry. We used linear mixed-effects models to compute variance components and evaluate the association between UAs and selected factors. Results: The concentrations of UAs were fairly reproducible within individuals, with intraclass correlation coefficients (ICCs) of 0.41, 0.35, 0.47, and 0.49 for inorganic As (InAs), MMA, DMA, and total urinary As (TUA). However, when expressed as a ratio, the percent InAs (%InAs), %MMA, and %DMA were poorly reproducible within individuals, with ICCs of 0.16, 0.16, and 0.17, respectively. Arsenic metabolism was significantly associated with sex, exposure, age, smoking, chewing betel nut, urinary creatinine, and season. Specificity and sensitivity analyses showed that a single urine sample adequately classified a participant's urinary As profile as high or low, but TUA had only moderate specificity for correctly classifying drinking water exposures. Conclusions: Epidemiologic studies should use both urinary As concentrations and the relative proportion of UAs to minimize measurement error and to facilitate interpretation of factors that influence As metabolism