A Dose-Response Study of Arsenic Exposure and Global Methylation of Peripheral Blood Mononuclear Cell DNA in Bangladeshi Adults

作者：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^*

来源：Environmental Health Perspectives, 2013, 121(11-12): 1306-1312.

DOI：10.1289/ehp.1206421

BACKGROUND: 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 non-linear relationship between As dose and DNA methylation.
OBJECTIVE: The objective of this study was to examine the dose-response relationship between As and global methylation of peripheral blood mono-nuclear cell (PBMC) DNA in apparently healthy Bangladeshi adults chronically exposed to a wide range of As concentrations in drinking water.
METHODS: 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 [H-3]-methyl incorporation assay, which provides disintegration-per-minute (DPM) values that are negatively associated with global DNA methylation.
RESULTS: Water, blood, and urinary As were positively correlated with global PBMC DNA methylation (p < 0.05). In multivariable-adjusted models, 1-mu g/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.
CONCLUSIONS: 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 under-lying mechanisms and physiologic implications.

• 出版日期2013-12