叔丁基对苯二酚对Chng肝细胞无机砷甲基化代谢的影响

目的 探讨叔丁基对苯二酚(tert-butylhydroquinone,tBHQ)对Chang肝细胞无机砷甲基化代谢的影响.方法 将Chang肝细胞密度调整为1×105个/ml,采用25μmol/LtBHQ溶液预处理24 h后,再用5 μmol/L的tBHQ溶液和0.1、0.5、1.0和5.0μmol/L亚砷酸钠溶液...     

无机砷和甲基化

无机砷既是一种毒物 ,又是一种抗癌药物。无机砷的许多作用机制与甲基化密切相关 ,无机砷的甲基化是其在人体内的主要代谢步骤之一 ;无机砷的致癌作用也与其引起基因的异常甲基化有关。本文对二者间的关系作一综述。     

叔丁基对苯二酚对亚砷酸钠致Chang liver细胞毒性的影响

目的 探讨叔丁基对苯二酚(tert-butylhydroquinone,tBHQ)对亚砷酸钠(NaAsO_2)致Chang liver细胞毒性的影响.方法 Chang liver细胞培养48 h后分别以20、40、60和80 μmo/L的NaAsO_2染毒24和48 h,作为NaAsO_2单独作用组.以5和20μmol/L的tBHQ预处理Chang liver细胞24h,以40和60μmol/L的NaAsO_2染毒24和48h,作为tBHQ预处理组;对照组处理同NaAsO_2:单独作用组.每个浓度设3个复孔.用Alamar Blue法检测细胞活力.结果 NaAsO_2单独作用24和48 h组Alamar Blue还原率显著下降,与对照组比较,差异有统计学意义(P<0.05);且NaAsO_2单独作用48 h组的Alamar Blue还原率均显著低于24 h组,差异有统计学意义(P＜0.01).5 μmol/L的tBHQ预处理组与对应的60 μmol/L NaAsO_2单独作用24h组相比,显著提高了Alamar Blue还原率(P＜0.01);20 μmol/L的tBHQ预处理组的Alamar Blue还原率均显著高于相对应NaAsO_2单独作用24 h组(P＜0.05).5 μmol/L的tBHQ预处理组的Alaraar Blue还原率均显著高于相对应NaAsO_2单独作用48h组(P＜0.01);20μmol/L的tBHQ预处理组与对应的40μmol/L NaAsO_2单独作用48h组相比,显著提高了Alamar Blue还原率(P<0.01).结论 tBHQ能够降低NaAsO_2致Chang liver细胞的毒性,增强细胞对NaAsO_2毒性的抵抗能力.

Abstract：

Objective To study the antagonism of text-butylhydroquinone (tBHQ)to NaAsO_2 induced cytotoxicity in Chang liver cells in vitro.Methods Chang liver cells were exposed to NaAsO_2(0,20,40,60 and 80μmol/L)for 24 and 48 hours,or Chang liver cells were treated with tBHQ(5 and 20 μmol/L),then exposed to NaAsO_2(40 and 60 μmol/L)for 24 and 48 hours.The conditions of control group was the same as NaAsO_2 group.Alamar Blue was used to evaluate the viabifity of cells.Results Chang liver cells were exposed to NaAsO_2 for 24 and 48 hours,Alamar Blue reduction rates decreased significantly and Alamar Blue reduction rates of 48 hours group were lower than 24 hours group (P<0.01).Alamar Blue reduction rate of 5 μmol/L tBHQ pretreatment group was higher than 60 μmol/L NaAsO_2 group for 24 h(P<0.01);Alamar Blue reduction rate of 20μmol/L tBHQ pretreatment group were higher than respective NaAsO_2 group for 24 h(P＜0.05).Alamar Blue reduction rate of 5 μmol/L tBHQ pretreatment group were higher than respective NaAsO_2 group for 48 h(P＜0.01);Alamar Blue reduction rate of 20 μmol/L tBHQ pretreatment group was higher than 40 μmol/L NaAsO_2 group for 48 h(P<0.01).Conclusion tBHQ can decrease the cytotoxieity induced by NaAsO_2 in Chang liver cells,increase the resistance to the cytotoxieity induced by NaAsO_2 in Chang liver cells.     

091 无机砷和甲基化

无机砷既是一种毒物,又是一种抗癌药物.无机砷的许多作用机制与甲基化密切相关,无机砷的甲基化是其在人体内的主要代谢步骤之一;无机砷的致癌作用也与其引起基因的异常甲基化有关.本文对二者间的关系作一综述.     

无机砷甲基化产物与砷代谢相关基因研究进展

砷对人体具有致癌性,与心血管疾病、糖尿病等疾病有关。砷在体内的代谢是一个极其复杂的过程,而调控砷代谢的相关基因在砷的代谢过程中起到了重要的作用,同时也解释了砷中毒的易感性问题。目前对于砷代谢的过程存在不同学说,对于砷代谢相关基因与砷代谢产物的关系以及砷中毒的易感性等问题,不同地区的报道也有差别。本文就砷甲基化的过程和产物、砷代谢相关基因研究的进展以及今后的研究方向展开阐述。     

人Chang肝细胞对亚砷酸钠蓄积和甲基化能力的研究

目的 探讨Chang肝细胞对砷的蓄积和甲基化能力.方法利用超低温捕集-氢化物发生-原子吸收分光光度法测定不同浓度(0.1、0.2、0.5 μmol/L)亚砷酸钠染毒条件下Chang肝细胞在培养24、48和72h时,细胞内和培养液中的不同形态砷化物含量.结果 同一染毒水平下,Chang肝细胞对砷的蓄积率随染毒时间的延长上升(P<0.05);24h各染毒剂量组对砷的蓄积率差异无统计学意义(P>05);48h0.1和0.2μmol/L染毒组对砷的蓄积率显著高于0.5μmol/L染毒组(P<0.05);72h0.1μmol/L染毒组对砷的蓄积率显著高于0.2和0.5μmol/L染毒组(P<0.05);72h0.1μmol/L染毒组细胞对砷的蓄积率最高,为13.78%.同等染毒剂量下,细胞对砷的甲基化率随染毒时间延长而升高(P<0.05);同一染毒时段,0.5μmol/L染毒组细胞甲基化率显著低于0.1和0.2μmol/L染毒组(P<0.05).结论 Chang肝细胞对砷的蓄积和甲基化能力较弱,且随染毒剂量升高,Chang肝细胞对砷的蓄积和甲基化能力呈下降趋势.     

无机砷甲基化产物毒性及其影响因素研究进展

曾有研究认为,无机砷的毒性远远大于有机砷,故将无机砷在机体内的甲基化看作是一解毒过程.张爱华等研究表明,砷中毒患者病情越重,其尿中无机砷浓度越高,占尿总砷的比重也越大.但又有研究提出,甲基化的中间产物--甲基亚胂酸（MMAsⅢ）的毒性大于无机砷.因此,探讨无机砷甲基化产物的毒性及其影响因素,对进一步认识砷的毒作用机制非常重要.本文对无机砷甲基化产物毒性及其影响因素研究进展综述如下.     

叔丁基对苯二酚对苯诱导的大鼠骨髓细胞毒性的保护作用

目的探讨叔丁基对苯二酚(tBHQ)对苯诱导的骨髓细胞毒性的保护作用。方法体外培养的大鼠骨髓细胞随机分为对照组和tBHQ预处理组,对照组:以不同浓度(0、5、10、15、20mmolL)苯分别染毒骨髓细胞2、4、6h;tBHQ预处理组:骨髓细胞染苯前先行tBHQ(100μmolL)预处理12h。单细胞凝胶电泳法检测骨髓细胞DNA损伤,流式细胞仪检测骨髓细胞凋亡率,2,6二氯靛酚还原法测定苯染毒前两组骨髓细胞内依赖还原型辅酶ⅠⅡ醌氧化还原酶(NQO1)的活力。结果对照组中随苯染毒浓度的增加、染毒时间的延长,骨髓细胞DNA损伤增强,细胞凋亡率增加。tBHQ预处理组中5、10、15、20mmolL苯染毒骨髓细胞的DNA迁移率和迁移度低于同浓度、同时间点的对照组,差异有统计学意义(P<0.05);15、20mmolL苯染毒2h及10、15、20mmolL苯染毒4h和5、10、15、20mmolL苯染毒6h骨髓细胞的凋亡率较同浓度、同时间点的对照组降低,差异有统计学意义(P<0.05);tBHQ预处理组骨髓细胞内NQO1活力(1.62±0.16mgpro-1·min-1)高于对照组(0.95±0.08mgpro-1·min-1),差异有统计学意义(P<0.01)。结论苯可诱导体外培养的大鼠骨髓细胞DNA损伤和细胞凋亡,并呈现一定的时间、剂量依赖性;tBHQ可诱导骨髓细胞NQO1活力增强,对苯诱导的骨髓细胞毒性有保护作用。     

叔丁基对苯二酚对百草枯神经细胞毒性和氧化应激的拮抗作用

目的 研究叔丁基对苯二酚(tBHQ)预处理对百草枯(PQ)致大鼠肾上腺嗜铬细胞瘤(PC12)细胞毒性和氧化应激的拮抗作用.方法 将PC12细胞分为溶剂对照组及100、300 μmol PQ处理组.用终浓度为40 μmol/LtBHQ预处理PC12细胞4 h再分别用终浓度0、100、300 μmol/L PQ处理细胞24或48 h,用噻唑蓝(MTT)法检测细胞毒性,用Annexin V-FITC/PI法流式细胞仪(FCM)检测细胞凋亡,用硫代巴比妥酸法测定细胞丙二醛(MDA)含量.结果 用40μmol/LtBHQ预处理后再用100、300μ,mol/L PQ处理PC12细胞24 h细胞存活率分别较100、300 μmol/L PQ组增高,差异有统计学意义(P＜0.05,P＜0.01);用40μmol/LtBHQ预处理后再用100μmol/LPQ处理PC12细胞48 h细胞存活率较100μmol/LPQ处理组细胞存活率增高,差异有统计学意义(P＜0.01);用40μmol/LtBHQ预处理后再用100、300μmol/PQ处理PC12细胞24 h后,细胞凋亡率分别较100、300 μmol/L PQ下降,差异有统计学意义(P＜0.05,P＜0.01);用40μmol/LtBHQ预处理后再用100、300μmol/LPQ处理PC12细胞24 h后,MDA含量分别较100、300 μmol/L PQ组下降,MDA含量分别为相应对照组的0.61、0.57倍,差异有统计学意义(P＜0.05).结论 tBHQ预处理可削弱PQ致PC12细胞的细胞毒性、细胞凋亡以及氧化应激作用.

Abstract：

Objective To investigate the protective effects of the tert-butylhydroquinone (tBHQ)pretreatment on neurotoxicity and oxidative stress induced by paraquat (PQ) in PC12 cells. Methods Cytoyoxicity of PC12 cells was measured by MTT assay, following the PC12 cells treatment with different concentrations of 100, 300 μmol/L PQ for 24 h and 48 h. PC12 cells were pretreated with or without 40 μmol/L tBHQ for 4 h, PC 12 cells were exposed to PQ at the doses of 0, 100, 300 μmol/L for 24 h and 48 h, respectively.The viability of PC 12 cells was measured by MTT assay, the apoptosis rates of PC 12 cells were detected by flow cytometry (FCM) and the malondialdehyde (MDA) levels of PC 12 cells were examine by thiobarbituric acid (TBA) method. Results When the exposure doses of PQ were 100 and 300 μmol/L for 24 h, the viability of PC 12 cells pretreated with tBHQ was significantly higher than that of PC 12 cells only exposed to PQ (P＜0.05 or P＜0.01). When the exposure dose of PQ was 100μmol/L for 48 h, the viability of PC12 cells pretreated with tBHQ was significantly higher than that of PC12 cells only exposed to PQ (P＜0.01). When the exposure doses of PQ were 100 and 300 μmol/L for 24 h, the apoptosis rates and MDA levels of PC12 cells pretreated with tBHQ were significantly lower than those of PC12 cells only exposed to PQ (P＜0.05 or P＜0.01). Conclusions tBHQ preteatment can reduce the cytotoxicity, apoptosis and oxidative stress induced by PQ in PC12 cells.     

叔丁基对苯二酚对百草枯神经细胞毒性和氧化应激的拮抗作用

Objective To investigate the protective effects of the tert-butylhydroquinone (tBHQ)pretreatment on neurotoxicity and oxidative stress induced by paraquat (PQ) in PC12 cells. Methods Cytoyoxicity of PC12 cells was measured by MTT assay, following the PC12 cells treatment with different concentrations of 100, 300 μmol/L PQ for 24 h and 48 h. PC12 cells were pretreated with or without 40 μmol/L tBHQ for 4 h, PC 12 cells were exposed to PQ at the doses of 0, 100, 300 μmol/L for 24 h and 48 h, respectively.The viability of PC 12 cells was measured by MTT assay, the apoptosis rates of PC 12 cells were detected by flow cytometry (FCM) and the malondialdehyde (MDA) levels of PC 12 cells were examine by thiobarbituric acid (TBA) method. Results When the exposure doses of PQ were 100 and 300 μmol/L for 24 h, the viability of PC 12 cells pretreated with tBHQ was significantly higher than that of PC 12 cells only exposed to PQ (P＜0.05 or P＜0.01). When the exposure dose of PQ was 100μmol/L for 48 h, the viability of PC12 cells pretreated with tBHQ was significantly higher than that of PC12 cells only exposed to PQ (P＜0.01). When the exposure doses of PQ were 100 and 300 μmol/L for 24 h, the apoptosis rates and MDA levels of PC12 cells pretreated with tBHQ were significantly lower than those of PC12 cells only exposed to PQ (P＜0.05 or P＜0.01). Conclusions tBHQ preteatment can reduce the cytotoxicity, apoptosis and oxidative stress induced by PQ in PC12 cells.     

大米中总砷及无机砷含量分析

目的了解大米中砷的含量及分布。方法应用氢化物发生—原子荧光分析技术测定大米中总砷、无机砷,采用高压焖罐对大米样品进行消解测定总砷,用6mol/LHCl提取大米中无机砷,在3mol/LHCl条件下测定总无机砷。结果仪器检出限:总砷0.08ng/ml,无机砷0.10ng/ml;样品回收率:总砷90.5%～103.7%,无机砷为91.6%～105.5%;相对标准偏差:总砷4.1%～6.5%,无机砷4.2%～6.8%。所测大米中总砷含量范围为0.06～0.18mg/kg,无机砷含量范围为0.035～0.13mg/kg,无机砷占总砷的含量为42.5%～88.0%。结论在所检样品中,均检出无机砷与总砷,含量均在国家限量卫生标准以内。     

无机砷对Chang肝细胞株血红素单加氧酶-1 mRNA和蛋白表达的诱导作用

[目的]观察亚砷酸钠（sodium arsenite,NaAsO2）对Chang肝细胞株血红素单加氧酶-1（heme oxygenase-1,HO-1）mRNA和蛋白表达的诱导作用。[方法]以5μmol／L和10μmol／L的NaAsO2作用Chang肝细胞株2、6、12h和24h,分别用逆转录-聚合酶链反应（RT-PCR）和Western Blot法检测细胞内HO-1的mRNA和蛋白表达情况。[结果]5μmol／L和10μmol／LNaAs02暴露2h开始出现HO-1mRNA的诱导表达;6h的表达水平明显高于对照组和2h暴露组（P〈0．01）。其中,10μmol／LNaAsO2暴露12h和24h的mRNA表达均明显高于该浓度的6h暴露组（P〈0．01）;但24h的HO-1 mRNA表达水平与12h组相比没有明显升高。NaAsO2暴露诱导的HO-1蛋白表达则从6h开始出现,12h组明显高于6h组,24h组明显高于12h组（均P〈0．01）;5μmol／L和10μmol／L NaAsO2分别暴露6、12h和24h的HO-1蛋白表达量分别是对照组的2．80、9．34、18．15和3．97、12．92、23．29倍;此外,10μmol/LNaAsO2暴露12h和24h的HO-1 mRNA和蛋白表达均明显高于对应时间的5μmol／L组（P〈0．01）。[结论]NaAsO2暴露能够有效和持续性诱导Chang肝细胞株HO-1的mRNA和蛋白表达,是无机砷暴露的一种细胞保护性适应性反应。     

土壤中无机砷的超声提取-原子荧光测定法

目的 建立土壤中无机砷含量的超声提取-氧化物发生-原子荧光(HG-AFS)测定方法.方法 土壤样品经超声消解90min提取无机砷,以6 mol/L盐酸溶液为提取剂,以10 g/L硼氢化钾-5 g/L氢氧化钾为还原剂,以4%的盐酸作载流,采用HG-AFS法测定土壤中无机砷的含量.结果 砷的浓度在0.025～100μg/L...     

砷暴露人群总尿砷浓度与砷甲基化代谢水平关系的研究

目的探讨砷暴露人群总尿砷浓度与砷甲基化代谢水平间的相互关系。方法于2006年7月,选择在某工业性砷污染区居住5a以上并且近6个月内持续生活在该村的村民323人为研究对象,并分为儿童组(6～13岁)和成人组(18岁及以上)。采集空腹晨尿,采用氢化物发生-原子荧光法测定总砷(TAs)浓度,采用离子色谱氢化物发生原子荧光法测定尿中无机砷(InAs)、一甲基胂酸(MMA)和二甲基胂酸(DMA)含量。结果与成人组比较,儿童组尿中TAs含量、MMA相对百分比和MMA/InAs比值均较低,DMA相对百分比和DMA/MMA比值均较高,差异有统计学意义(P<0.01)。成人尿中TAs含量与MMA相对百分比和MMA/InAs的比值与尿TAs含量呈负相关(P<0.05),而DMA/MMA的比值与尿TAs含量呈正相关(P<0.01)。但儿童及18～39岁组尿中InAs、DMA、MMA相对百分比及DMA/MMA、MMA/InAs、OrgAs/InAs的比值与尿TAs含量未见统计学相关(P>0.05)。结论尿TAs浓度与砷的总甲基化水平可能呈负相关趋势,但年龄可能是这种相关趋势的混杂因素。     

无机砷生物转化与毒理学研究

无机砷在机体的代谢转化中存在明显的物种差异,甲基化产物在各器官、组织含量也存在差异。砷甲基化产物具有明显的毒性,尤其是遗传毒性。三价甲基胂酸可能是导致砷遗传毒性的关键物质,砷的代谢转化过程可能存在遗传毒性和致癌的早期关键事件。     

吸烟对人类砷代谢和甲基化影响的Meta分析

目的 探讨吸烟是否影响人类对砷的代谢和甲基化.方法 检索纳入有关吸烟和砷代谢产物关系的1994-2008年发表的文献6篇,应用随机效应模型和同定效应模型对吸烟与人尿中无机砷(iAs)、一甲基胂酸(MMA)、二甲基胂酸(DMA)含量占总砷百分比的关系进行综合的定量分析.结果 吸烟组尿中iAs百分比的合并加权均数差(weight meandifference,WMD)为0.59(95%CI:-0.01～1.18);吸烟组尿中MMA百分比的合并WMD为2.44(95%CI:1.95～2.94);吸烟组尿中DMA百分比的合并WMD为-3.04(95%CI:-4.01-2.07). Meta分析提示吸烟组尿中MMA百分比高于非吸烟组,而吸烟组尿中DMA百分比低于非吸烟组.结论 吸烟可能是人类对砷代谢和甲基化影响因素之一.

Abstract：

Objective To investigate whether smoking affects metabolism and methylation of arsenic. Methods Six papers about the relation between smoking and arsenic metabolism, methylation were collected until December,2008, and the data were quantitatively analyzed with random and fixed effect models. Results In the group of smoking, the summary weighted mean difference of percent of inorganic in urinary was 0.59 (95% CI:-0.01 - 1.18). The summary weighted mean difference of percent of MMA in urinary was 2.44 (95%CI:1.95 - 2.94). The summary weighted mean difference of percent of DMA in urinary was -3.04 (95%CI:-4.01 --2.07). Current evidence suggested that percent of MMA was higher, percent of DMA was lower in smoking or ever smoking group compared with nonsmoking group. Conclusion Smoking may be considered a risk factor for metabolism and methylation of arsenic on human.     

燃煤型砷中毒病区人群与非病区人群砷甲基化代谢水平的比较

目的 描述燃煤型砷中毒病区人群与非病区人群砷甲基化代谢的特征,比较两区人群砷甲基化代谢水平的差异.方法 于2005年12月随机抽取某燃煤型砷中毒病区常住居民228名(包括116名砷中毒确诊患者,内对照成人60名,14岁以下儿童52名),同时随机抽取非病区常住居民218名(外对照组成人149名,儿童69名),采集空腹晨尿,用离子色谱氢化物发生原子荧光法测定尿中无机砷(InAs)、一甲基胂酸(MMA)和二甲基胂酸(DMA).结果 燃煤型砷中毒病区人群砷的甲基化水平均显著低于非病区人群(P＜0.05),但病区病例组与内对照组之间未见显著差异.病区男性和女性砷的甲基化水平分别低于非病区男性和女性;病区男性对砷的甲基化能力低于女性,但非病区男性与女性之间比较,差异未见统计学意义.病区各年龄段人群砷的甲基化水平均低于非病区居民;随着年龄增加,MMA比例和MMA/InAs比值呈增加趋势,而DMA比例和DMA/MMA比值呈下降的趋势.结论 燃煤型砷中毒病区人群砷的甲基化水平低于非病区人群,男性和女性对砷的甲基化能力存在差异,砷甲基化代谢水平随着年龄增加呈下降趋势.     

青岛市市售海产品砷污染状况及无机砷暴露风险评估

目的 通过分析青岛市市售海产品中总砷及无机砷含量水平以及居民的海产品膳食摄入量，对本市市售海产品中的砷污染状况及人群无机砷暴露风险进行评估。方法 在全市采集215份海产品样品，采用氢化物发生原子荧光光谱法、液相色谱-原子荧光光谱法分别测得总砷及无机砷含量，并根据青岛市居民海产品平均摄入量，利用靶器官危害系数(THQ)对青岛市居民海产品中无机砷食用健康风险进行评估。结果 总砷含量由高到低依次为甲壳类、贝类、鱼类，无机砷含量由高到低依次为贝类、甲壳类、鱼类。2 007名青岛市居民的膳食调查结果显示，居民每日海产品摄入量均值为1.68 g/kg·bw。海产品中，贝类是居民摄入无机砷的主要来源。45～59岁男性组中，由于摄入较多的海产品，摄入水平较高的居民THQ值＞1，可认为存在一定的健康风险。结论 青岛市居民海产品的食用健康风险在安全范围内，但对于45～59岁年龄段中海产品摄入较高的男性居民而言，存在健康风险，应注意重点防范。     

A Prospective Study of Arsenic Exposure,Arsenic Methylation Capacity,and Risk of Cardiovascular Disease in Bangladesh

Background: Few prospective studies have evaluated the influence of arsenic methylation capacity on cardiovascular disease (CVD) risk.Objective: We evaluated the association of arsenic exposure from drinking water and arsenic methylation capacity with CVD risk.Method: We conducted a case–cohort study of 369 incident fatal and nonfatal cases of CVD, including 211 cases of heart disease and 148 cases of stroke, and a subcohort of 1,109 subjects randomly selected from the 11,224 participants in the Health Effects of Arsenic Longitudinal Study (HEALS).Results: The adjusted hazard ratios (aHRs) for all CVD, heart disease, and stroke in association with a 1-SD increase in baseline well-water arsenic (112 µg/L) were 1.15 (95% CI: 1.01, 1.30), 1.20 (95% CI: 1.04, 1.38), and 1.08 (95% CI: 0.90, 1.30), respectively. aHRs for the second and third tertiles of percentage urinary monomethylarsonic acid (MMA%) relative to the lowest tertile, respectively, were 1.27 (95% CI: 0.85, 1.90) and 1.55 (95% CI: 1.08, 2.23) for all CVD, and 1.65 (95% CI: 1.05, 2.60) and 1.61 (95% CI: 1.04, 2.49) for heart disease specifically. The highest versus lowest ratio of urinary dimethylarsinic acid (DMA) to MMA was associated with a significantly decreased risk of CVD (aHR = 0.54; 95% CI: 0.34, 0.85) and heart disease (aHR = 0.54; 95% CI: 0.33, 0.88). There was no significant association between arsenic metabolite indices and stroke risk. The effects of incomplete arsenic methylation capacity—indicated by higher urinary MMA% or lower urinary DMA%—with higher levels of well-water arsenic on heart disease risk were additive. There was some evidence of a synergy of incomplete methylation capacity with older age and cigarette smoking.Conclusions: Arsenic exposure from drinking water and the incomplete methylation capacity of arsenic were adversely associated with heart disease risk.     

Influence of Cobalamin on Arsenic Metabolism in Bangladesh

Background

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.

Objective

We examined the associations between plasma cobalamin and uAs metabolites.

Methods

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.

Results

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.

Conclusions

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.