Hall Megan N, Liu Xinhua, Slavkovich Vesna, Ilievski Vesna, Pilsner J Richard, Alam Shafiul, Factor-Litvak Pam, Graziano Joseph H, Gamble Mary V
Department of Epidemiology, Columbia University, New York, New York 10032, USA.
Environ Health Perspect. 2009 May;117(5):825-31. doi: 10.1289/ehp.0800164. Epub 2009 Jan 15.
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.
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).
Children provided blood samples for measurement of tHcys, folate, cobalamin, and cysteine, and urine specimens for the measurement of total uAs and As metabolites.
Consistent with our studies in adults, mean tHcys concentrations (7.9 micromol/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).
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.
孟加拉国约有3500万人长期饮用含有无机砷（InAs）的水。InAs甲基化为一甲基胂酸（MMA）和二甲基胂酸（DMA）依赖于叶酸依赖性一碳代谢，并有助于尿砷（uAs）的排泄。
我们在165名6岁孟加拉国儿童样本中研究了叶酸、钴胺素、半胱氨酸、总同型半胱氨酸（tHcys）和uAs代谢物之间的关系。
儿童提供血样用于测定tHcys、叶酸、钴胺素和半胱氨酸，提供尿样用于测定总uAs和砷代谢物。
与我们对成年人的研究一致，平均tHcys浓度（7.9微摩尔/升）高于其他人群中类似年龄儿童的报告值。19%的儿童血浆叶酸浓度<9.0纳摩尔/升。以InAs形式排泄的总uAs比例（%InAs）与叶酸（r = -0.20，p = 0.01）和半胱氨酸（r = -0.23，p = 0.003）呈负相关，而%DMA与叶酸（r = 0.12，p = 0.14）和半胱氨酸（r = 0.11，p = 0.15）的相关性为正。同型半胱氨酸与男性的%MMA呈负相关（r = -0.27，p = 0.009），与%DMA的相关性为正（r = 0.13，p = 0.10）。
这些发现表明，与成年人一样，叶酸和半胱氨酸有助于儿童体内砷的甲基化。然而，tHcys与%MMA的负相关以及与%DMA的正相关，均与我们之前对成年人的研究结果相反。我们认为，一碳代谢的上调可能是为了满足快速生长期间对DNA和蛋白质生物合成的大量需求，这导致了tHcys生物合成增加以及砷甲基化增加。
