A dose-response study of arsenic exposure and global methylation of peripheral blood mononuclear cell DNA in Bangladeshi adults

• Published in: Environmental health perspectives 2013-11, Vol.121 (11-12), p.1306-1312
• Main Authors: Niedzwiecki, Megan M, Hall, Megan N, Liu, Xinhua, Oka, Julie, Harper, Kristin N, Slavkovich, Vesna, Ilievski, Vesna, Levy, Diane, van Geen, Alexander, Mey, Jacob L, Alam, Shafiul, Siddique, Abu B, Parvez, Faruque, Graziano, Joseph H, Gamble, Mary V
• Format: Article
• Language: English
• Subjects: Adult; Adults; Animal models; Arsenic; Arsenic - blood; Arsenic - toxicity; Arsenic - urine; Bangladesh; Blood; Blood cells; Chromatography, High Pressure Liquid; Colorimetry; Creatinine; Deoxyribonucleic acid; DNA; DNA methylation; DNA Methylation - drug effects; DNA repair; Dose-response relationship (Biochemistry); Dose-Response Relationship, Drug; Drinking water; Drinking Water - adverse effects; Drinking Water - chemistry; Environmental Exposure - adverse effects; Female; Folic Acid - blood; Genes; Genetic aspects; Genetic testing; Health; Health aspects; Homocysteine - blood; Humans; Laboratories; Leukocytes, Mononuclear - drug effects; Male; Mass Spectrometry; Medical research; Medicine, Experimental; Methylation; Middle Aged; Oxidative stress; Plasma; Population; S-Adenosylmethionine - blood; Statistics, Nonparametric; Studies; Tritium; Urine; Vitamin B; Water Pollutants, Chemical - analysis; Water Pollutants, Chemical - toxicity
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp.1206421

Several studies employing cell culture and animal models have suggested that arsenic (As) exposure induces global DNA hypomethylation. However, As has been associated with global DNA hypermethylation in human study populations. We hypothesized that this discrepancy may reflect a nonlinear relationship between As dose and DNA methylation. The objective of this study was to examine the dose-response relationship between As and global methylation of peripheral blood mononuclear cell (PBMC) DNA in apparently healthy Bangladeshi adults chronically exposed to a wide range of As concentrations in drinking water. Global PBMC DNA methylation, plasma folate, blood S-adenosylmethionine (SAM), and concentrations of As in drinking water, blood, and urine were measured in 320 adults. DNA methylation was measured using the [3H]-methyl incorporation assay, which provides disintegration-per-minute (DPM) values that are negatively associated with global DNA methylation. Water, blood, and urinary As were positively correlated with global PBMC DNA methylation (p < 0.05). In multivariable-adjusted models, 1-μg/L increases in water and urinary As were associated with 27.6-unit (95% CI: 6.3, 49.0) and 22.1-unit (95% CI: 0.5, 43.8) decreases in DPM per microgram DNA, respectively. Categorical models indicated that estimated mean levels of PBMC DNA methylation were highest in participants with the highest As exposures. These results suggest that As is positively associated with global methylation of PBMC DNA over a wide range of drinking water As concentrations. Further research is necessary to elucidate underlying mechanisms and physiologic implications.