Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York 10032, USA.
Environ Health Perspect. 2009 Nov;117(11):1724-9. doi: 10.1289/ehp.0900734. Epub 2009 Jul 31.
Arsenic is a carcinogen to which 35 million people in Bangladesh are chronically exposed. The enzymatic transfer of methyl groups to inorganic As (iAs) generates monomethylarsonic (MMA) and dimethylarsinic acids (DMA) and facilitates urinary As (uAs) elimination. This process is dependent on one-carbon metabolism, a pathway in which folate and cobalamin have essential roles in the recruitment and transfer of methyl groups. Although DMA(V) is the least toxic metabolite, increasing evidence suggests that MMA(III) may be the most cytotoxic and genotoxic As intermediary metabolite.
We examined the associations between plasma cobalamin and uAs metabolites.
We conducted a cross-sectional study of 778 Bangladeshi adults in which we over-sampled cobalamin-deficient participants. Participants provided blood samples for the measurement of plasma cobalamin and urine specimens for As measurements.
Cobalamin was inversely associated with the proportion of total uAs excreted as iAs (%iAs) [unstandardized regression coefficient (b) = -0.10; 95% confidence interval (CI), -0.17 to -0.02; p = 0.01] and positively associated with %MMA (b = 0.12; 95% CI, 0.05 to 0.20; p = 0.001). Both of these associations were stronger among folate-sufficient participants (%iAs: b = -0.17; 95% CI, -0.30 to -0.03; p = 0.02. %MMA: b = 0.20; 95% CI, 0.11 to 0.30; p < 0.0001), and the differences by folate status were statistically significant.
In this group of Bangladeshi adults, cobalamin appeared to facilitate the first As methylation step among folate-sufficient individuals. Given the toxicity of MMA(III), our findings suggest that in contrast to folate, cobalamin may not favorably influence As metabolism.
砷是一种致癌物质，孟加拉国有 3500 万人长期接触砷。无机砷（iAs）的酶促甲基转移生成一甲基砷酸（MMA）和二甲基砷酸（DMA），并促进尿砷（uAs）排泄。这个过程依赖于一碳代谢，叶酸和钴胺素在招募和转移甲基基团方面具有重要作用。尽管 DMA(V) 是毒性最小的代谢物，但越来越多的证据表明 MMA(III) 可能是最具细胞毒性和遗传毒性的砷中间代谢物。
我们研究了血浆钴胺素与 uAs 代谢物之间的关系。
我们对 778 名孟加拉国成年人进行了横断面研究，其中我们过度采样了钴胺素缺乏的参与者。参与者提供血液样本以测量血浆钴胺素和尿液样本以测量砷。
钴胺素与总 uAs 排泄为 iAs 的比例呈负相关（%iAs）[未标准化回归系数（b）=-0.10；95%置信区间（CI）=-0.17 至-0.02；p=0.01]，与 %MMA 呈正相关（b=0.12；95%CI，0.05 至 0.20；p=0.001）。在叶酸充足的参与者中，这两种关联更强（%iAs：b=-0.17；95%CI，-0.30 至-0.03；p=0.02。%MMA：b=0.20；95%CI，0.11 至 0.30；p<0.0001），且叶酸状态差异具有统计学意义。
在这群孟加拉国成年人中，钴胺素似乎促进了叶酸充足个体的第一个砷甲基化步骤。考虑到 MMA(III) 的毒性，我们的发现表明，与叶酸不同，钴胺素可能不会对砷代谢产生有利影响。
