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Megan N. Hall,¹ Xinhua Liu,² Vesna Slavkovich,³ Vesna Ilievski,³ J. Richard Pilsner,⁴ Shafiul Alam,⁵ Pam Factor-Litvak,¹ Joseph H. Graziano,³ and Mary V. Gamble³

¹Department of Epidemiology, ²Department of Biostatistics, and ³Department of Environmental Health Sciences, Columbia University, New York, New York, USA; ⁴Department of Epidemiology, University of Michigan, Ann Arbor, Michigan, USA; ⁵Columbia University Arsenic Project, Bangladesh, Dhaka, Bangladesh

Abstract
Background: Approximately 35 million people in Bangladesh are chronically exposed to inorganic arsenic (InAs) in drinking water. Methylation of InAs to monomethylarsonic (MMA) and dimethylarsinic acids (DMA) relies on folate-dependent one-carbon metabolism and facilitates urinary arsenic (uAs) elimination.

Objectives: We examined the relationships between folate, cobalamin, cysteine, total homocysteine (tHcys) , and uAs metabolites in a sample of 6-year-old Bangladeshi children (n = 165) .

Methods: Children provided blood samples for measurement of tHcys, folate, cobalamin, and cysteine, and urine specimens for the measurement of total uAs and As metabolites.

Results: Consistent with our studies in adults, mean tHcys concentrations (7.9 µmol/L) were higher than those reported among children of similar ages in other populations. Nineteen percent of the children had plasma folate concentrations < 9.0 nmol/L. The proportion of total uAs excreted as InAs (%InAs) was inversely correlated with folate (r = –0.20, p = 0.01) and cysteine (r = –0.23, p = 0.003) , whereas the correlations between %DMA and both folate (r = 0.12, p = 0.14) and cysteine (r = 0.11, p = 0.15) were positive. Homocysteine was inversely correlated (r = –0.27, p = 0.009) with %MMA in males, and the correlation with %DMA was positive (r = 0.13, p = 0.10) .

Conclusions: These findings suggest that, similar to adults, folate and cysteine facilitate As methylation in children. However, the inverse correlation between tHcys and %MMA, and positive correlation with %DMA, are both opposite to our previous findings in adults. We propose that upregulation of one-carbon metabolism, presumably necessary to meet the considerable demands for DNA and protein biosynthesis during periods of rapid growth, results in both increased tHcys biosynthesis and increased As methylation.

Key words: arsenic, Bangladesh, children, cobalamin, creatinine, cysteine, dimethylarsinic acid, folate, homocysteine, monomethylarsonic acid, one-carbon metabolism. Environ Health Perspect 117:825–831 (2009) . doi:10.1289/ehp.0800164 available via http://dx.doi.org/ [Online 15 January 2009]

Address correspondence to M. Gamble, Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 60 Haven Ave., B-1, New York, NY 10032 USA. Telephone: (212) 305-7949. Fax: (212) 305-3857. E-mail: mvg7@columbia.edu

Supplemental Material is available online at http://www.ehponline.org/members/2009/0800164/suppl.pdf

We thank our staff, fieldworkers, and study participants in Bangladesh, without whom this work would not have been possible.

This work was supported by grants RO1 ES011601, 5P30ES09089, 1 P42 ES10349, and CA094061-07 from the National Institutes of Health.

The authors declare they have no competing financial interests.

Received 8 September 2008 ; accepted 15 January 2009.