Associations of plasma selenium with arsenic and genomic methylation of leukocyte DNA in Bangladesh.
Associations of plasma selenium with arsenic and genomic methylation of leukocyte DNA in Bangladesh.
复制标题
DOI：
10.1289/ehp.1001937
复制
发表时间：
2011-01
影响因子：
10.4
通讯作者：
Gamble MV
中科院分区：
文献类型：
--
作者：
Pilsner JR;Hall MN;Liu X;Ahsan H;Ilievski V;Slavkovich V;Levy D;Factor-Litvak P;Graziano JH;Gamble MV
DNA的整体低甲基化被认为是某些癌症的早期事件，在体外和动物模型中都是对砷（As）暴露和/或硒（Se）缺乏的反应。此外，砷和硒之间的拮抗作用，即各自降低对方的毒性，已在动物模型中得到充分证明。因此，硒状况可能改变砷暴露人群中砷对健康的影响。本研究的主要目的是验证硒缺乏与淋巴细胞DNA基因组低甲基化相关的假设，并确定在孟加拉国暴露于砷污染地下水的成年人中，硒水平是否与血液中砷（bAs）和尿液中砷（uAs）浓度相关。第二个目的是探索血浆硒和砷代谢产物之间的关系。在一项对287名成年人的横断面研究中，我们评估了血浆硒浓度、血液和尿液中的砷代谢物谱以及白细胞DNA的基因组甲基化。在调整潜在混杂因素后，我们观察到硒（微克/升）与基因组DNA甲基化（每1 μg/L硒增加每分钟崩解）之间的负相关：β = 345.6；95%置信区间（CI）， 59-632。硒浓度与血液（β = - 0.04, 95% CI, - 0.08至- 0.01）和尿液（β = - 20.1, 95% CI, - 29.3至- 10.9）中的总砷浓度（微克/升）呈负相关。硒水平与血液中一甲基larsinic酸的百分比呈负相关（β = - 0.59, 95% CI, - 1.04 ~ - 0.13），与二甲基larsinic酸的百分比呈正相关（β = 0.53, 95% CI, 0.04 ~ 1.01）。我们的研究结果表明硒与基因组DNA甲基化呈负相关。这一观察的潜在机制和影响尚不清楚，需要进一步调查。此外，硒可能影响bAs和was浓度，以及血液中as代谢物的相对比例。
Global hypomethylation of DNA is thought to constitute an early event in some cancers and occurs in response to arsenic (As) exposure and/or selenium (Se) deficiency in both in vitro and animal models. In addition, antagonism between As and Se, whereby each reduces toxicity of the other, has been well documented in animal models. Se status may therefore modify the health effects of As in As-exposed populations. The primary objectives of our study were to test the hypothesis that Se deficiency is associated with genomic hypomethylation of lymphocyte DNA and to determine whether Se levels are associated with blood As (bAs) and urinary As (uAs) concentrations in adults exposed to As-contaminated groundwater in Bangladesh. A secondary objective was to explore the relationships between plasma Se and As metabolites. We assessed plasma Se concentrations, As metabolite profiles in blood and urine, and genomic methylation of leukocyte DNA in a cross-sectional study of 287 adults. After adjustment for potential confounders, we observed an inverse association between Se (micrograms per liter) and genomic DNA methylation (disintegrations per minute per 1-μg/L increase in Se): β = 345.6; 95% confidence interval (CI), 59–632. Se concentrations were inversely associated with total As concentrations (micrograms per liter) in blood (β = −0.04; 95% CI, −0.08 to −0.01) and urine (β = −20.1; 95% CI, −29.3 to −10.9). Se levels were negatively associated with the percentage of monomethylarsinic acid (β = −0.59; 95% CI, −1.04 to −0.13) and positively associated with the percentage of dimethylarsinic acid (β = 0.53; 95% CI, 0.04 to 1.01) in blood. Our results suggest that Se is inversely associated with genomic DNA methylation. The underlying mechanisms and implications of this observation are unclear and warrant further investigation. In addition, Se may influence bAs and uAs concentrations, as well as relative proportions of As metabolites in blood.
登录
查看更多内容
影响因子：
10.4
作者：
Frisbie SH;Mitchell EJ;Mastera LJ;Maynard DM;Yusuf AZ;Siddiq MY;Ortega R;Dunn RK;Westerman DS;Bacquart T;Sarkar B
通讯作者：
Sarkar B
影响因子：
4.2
作者：
Davis, CD;Uthus, EO
通讯作者：
Uthus, EO
影响因子：
3.9
作者：
Gailer, Juergen
通讯作者：
Gailer, Juergen
影响因子：
15
作者：
Gailer, J;George, GN;Aposhian, HV
通讯作者：
Aposhian, HV
DOI：
10.1006/bbrc.1997.6618
发表时间：
1997-05-19
影响因子：
3.1
作者：
Hill, KE;McCollum, GW;Burk, RF
通讯作者：
Burk, RF