砷接触工人尿甲基砷酸水平与P53基因损伤的关系

[目的]观察砷职业暴露人群尿甲基砷酸水平与P53基因损伤的关系,深入认识砷的遗传毒性。[方法]选取砒霜厂95名砷接触工人作为暴露组,另选对照组55人,采集外周血和晨尿。用氢化物发生原子吸收分光光度法检测尿中各形态砷化合物和总砷含量,并计算一、二级甲基化指数。实时荧光定量PCR扩增人群外周血淋巴细胞P53基因外显子5和8,通过循环阈值推算损伤后扩增效率,间接计算损伤指数。[结果]暴露组工人尿中无机砷（iAs）、甲基砷酸（MMA）、二甲基砷酸（DMA）均明显高于对照组;暴露组工人二级甲基化指数明显低于对照组;暴露组工人P53基因外显子5和8的损伤指数均明显高于对照组;尿中砷一级甲基化指数与P53基因第5外显子损伤指数存在明显的正相关,尿中砷二级甲基化指数与P53基因第5外显子损伤指数存在明显的负相关。[结论]职业砷暴露工人二级甲基化指数明显增加,体内存在较多甲基砷酸,可能是P53基因外显子5损伤的主要原因。     

砒霜厂工人外周血淋巴细胞Dicer基因相对表达与尿砷代谢产物的关系研究

目的 通过比较职业性砷暴露人群与对照人群外周血淋巴细胞Dicer基因表达的差异,探讨职业性砷暴露人群外周血淋巴细胞中Dicer基因的表达与尿砷代谢产物之间的关系.方法 于2011年选取43名砒霜厂职业性砷暴露工人为暴露组,23名无砷暴露史人群为对照组,采用TRIzol法提取淋巴细胞中的总RNA,利用实时荧光定量PCR方法检测Dicer基因的表达,采用氢化物发生原子吸收分光光度法检测尿中各类砷化合物的含量.结果 砒霜厂工人无机砷、甲基胂酸、二甲基胂酸、总砷含量均高于对照组,二级甲基化指数低于对照组,外周血淋巴细胞中Dicer基因mRNA的表达(6.90±0.24)高于对照组(5.08±0.24),差异均有统计学意义(P＜0.01).尿中无机砷、甲基胂酸、二甲基胂酸、总砷与外周血淋巴细胞中Dicer基因mRNA表达呈正相关(P＜0.01);二级甲基化指数与Dicer基因mRNA表达呈负相关(r=-0.384,P＜0.05).结论 职业性砷暴露工人外周血淋巴细胞Dicer基因表达升高,可能与砷代谢甲基化过程有关.     

砷冶炼厂工人肿瘤相关基因mRNA表达变化

目的探讨砷冶炼厂工人肿瘤相关基因mRNA表达变化规律及影响因素。方法选择在岗砷冶炼工人37名、停止砷冶炼85天的工人43名和对照组51名为研究对象,使用带砷预处理系统的原子吸收分光光度法检测研究对象尿中无机砷、甲基胂酸和二甲基胂酸含量;实时荧光定量聚合酶链式反应(PCR)检测研究对象外周血Lin28、Bax、Bcl-2、Fas基因的mRNA相对表达量。结果尿中无机砷、甲基胂酸和二甲基胂酸浓度分别为:在岗砷冶炼工人(133.97±109.53)、(208.93±171.43)和(820.35±487.39)μg/g肌酐;停止砷冶炼工人(123.31±112.72)、(176.21±157.19)和(467.73±392.17)μg/g肌酐;对照组(1.55±1.49)、(0.10±0.09)和(10.47±7.85)μg/g肌酐。砷接触组工人尿中3种砷化合物浓度均显著高于对照组,正在进行砷冶炼的工人二甲基胂酸浓度显著高于停止砷冶炼工人(P0.05)。研究对象相应外周血Lin28、Bax、Bcl-2、Fas基因的mRNA相对表达量分别为:在岗砷冶炼工人(8.88±2.42)、(6.87±1.10)、(7.24±2.31)和(8.23±2.90);停止砷冶炼工人(6.21±2.94)、(5.81±1.72)、(4.50±1.59)和(6.89±2.35);对照组(5.60±1.43)、(5.56±0.98)、(4.88±1.39)和(6.92±1.87)。在岗砷冶炼工人Lin28、Bax、Bcl-2、Fas基因的mRNA相对表达量均显著高于对照组(P0.05)。结论砷冶炼工人多种肿瘤相关基因mRNA高表达,无机砷甲基化代谢转化在相关mRNA高表达中具有重要作用。     

砒霜厂男性工人外周血淋巴细胞Fas和Bax基因表达水平与尿砷代谢产物的关系

目的探讨职业性砷暴露人群外周血淋巴细胞中Fas和Bax基因的表达与尿砷代谢产物之间的关系。方法于2011年10月,选取云南某砒霜厂全部43名职业性砷暴露男性工人为暴露组以及23名无砷暴露史男性人群为对照组。测定尿中无机砷、甲基胂酸、二甲基胂酸和外周血淋巴细胞Fas和Bax m RNA的表达水平。结果与对照组比较,砒霜厂工人尿中无机砷、甲基胂酸、二甲基胂酸、总砷及外周血淋巴细胞中Fas和Bax m RNA的表达水平均较高,二级甲基化指数较低,差异均有统计学意义(P0.05)。尿中无机砷、甲基胂酸,二甲基胂酸、总砷与Fas和Bax m RNA表达水平呈正相关(均P0.05),尿砷一级甲基化指数仅与Fas m RNA表达水平呈正相关(P0.05);尿中砷二级甲基化指数与Fas和Bax m RNA表达水平呈负相关(均P0.05)。结论职业性砷暴露工人外周血淋巴细胞中Fas和Bax基因表达升高可能与砷甲基化代谢相关。     

冶炼厂工人p15基因表达与砷及其代谢产物的关系

为探讨尿砷及其代谢产物对p15基因表达的影响,选取某砷冶炼厂76名一线作业工人为暴露组,非职业环境砷暴露的22名当地居民为对照组,采用原子吸收分光光度法检测尿砷各形态水平,计算一、二级甲基化指数;使用qRT PCR法检测外周血中淋巴细胞p15 mRNA的表达情况。结果显示,砷冶炼厂工人尿中无机砷(iAs)、一甲基胂酸(MMA)、二甲基胂酸(DMA)、总砷水平均高于对照组,二级甲基化指数(SMI)低于对照组,p15 mRNA的相对表达水平高于对照组,差异均有统计学意义(P005);尿中iAs (r=0492)、 MMA(r=0531)、 DMA (r=0526)、总砷(r=0531)、 MMA%(r=0340)与p15基因相对表达呈正相关(P005),p15的表达受SMI的影响且呈负相关(r=-0256),差异具有统计学意义(P005)。说明砷可导致职业接触人群中p15基因的相对表达上调,并且存在一定的剂量关系。     

某锡冶炼企业接砷工人尿砷水平分析

从某锡冶炼厂随机选择健康的职工作为研究对象,采用氢化物发生原子荧光光谱法检测尿中砷含量。尿砷中位数为268.34μg/L,男女尿砷中位数分别为274.97μg/L、250.01μg/L,差异无统计学意义(P0.05)。尿砷含量与工龄、年龄均不相关(P0.05),且各车间工人尿砷含量差异亦无统计学意义。尿砷超标工人的临床表现以类神经症和皮肤损害为主,提示应加强暴露人群尿砷监测,发现高危人群及时调离砷接触岗位。     

尿形态砷在砷暴露员工职业健康检查中的应用研究

目的通过对职业砷暴露作业工人健康指标及尿总砷(TAs)、尿形态砷水平测定分析,初步揭示人体内形态砷对人体健康的影响。方法选择2家有色金属冶炼企业(铅冶炼、锡冶炼各1)砷暴露作业工人(暴露组)137人为研究对象。暴露组中铅冶炼组40人,锡冶炼组97人;无砷接触者(小学教师)42人为对照组,进行尿总砷及尿价态砷测定及健康监护,并测定作业场所砷化合物浓度。并对尿总砷、尿价态砷与健康检查结果进行分析。结果暴露组锡、铅两冶炼厂检测岗位平均砷化合物浓度均超过国家职业卫生标准,分别为0.52 mg/m3、0.20 mg/m3;暴露组的TAs、DMA(二甲基砷酸盐)含量与对照组比较差异有统计学意义(P<0.01);暴露组及对照组尿中价态砷主要以DMA为主,均占形态砷含量的90%以上;车间空气中的砷化合物浓度与砷暴露工人尿总砷、DMA成正相关关系。随着总砷、DMA浓度的升高,转氨酶升高、血红细胞下降趋势;肝脏B超及心电图异常检出率亦随之升高。结论砷暴露的作业工人随着接触砷浓度增高,体内总砷、DMA随之增高,形态砷(特别是DMA)对肝脏、心脏、肾脏、红细胞等损害作用越明显。说明形态砷(特别是DMA)与砷暴露作业工人身体健康有一定的关系,因此,为进一步阐明形态砷的毒性作用,有必要在砷暴露作业工人职业健康体检中行尿形态砷检查。     

铜矿冶炼工人尿中砷含量及影响因素分析

目的了解铜矿工人砷暴露情况,分析影响尿砷水平的因素,为采取防控措施、保护工人健康提供科学数据。方法随机选取某铜矿冶炼厂工人151人,将工人按照工种分为地上作业和地下开采2组,采用问卷调查的方式了解工人一般状况,并测量身高、体质量和血压,采用阱捕集-氢化物发生-原子吸收分光光度计测定尿中各种砷化物含量。结果地下开采工人吸烟率和饮酒量(84.3%、194.8g)明显高于地上作业工人(69.1%、104g),差异有统计学意义(P0.05)。地上作业工人尿中无机砷(iAs)、二甲基砷酸(DMA)和总砷(TAs)水平[(7.1±3.6)、(65.4±34.1)、(79.8±40.6)μg/g Cr]明显高于地下开采工人[(4.8±3.5)、(46.6±37.5)、(57.3±45.0)μg/g Cr](P0.01),而两组工人的砷甲基化代谢能力无明显差异(P0.05)。近3日食用海产品的工人尿中DMA和TAs水平[(60.8±41.0)、(73.3±49.6)μg/g Cr]明显高于未食用海产品的工人[(49.1±31.7)、(61.3±38.7)μg/g Cr]。年龄大、工龄长和近3日食用海产品和饮酒的工人二甲基化能力增强,二甲基指数(SMI)明显增高[50岁为(0.907±0.058),工龄10a为(0.903±0.050),近3日食用海产品的为(0.912±0.051]。在控制了年龄、工龄、吸烟、饮酒、高血压、近3日食用海产品等因素后,工作种类和体质量指数(BMI)是影响工人尿砷超标的危险因素。结论铜矿开采和冶炼增加工人砷暴露,地上作业和高BMI是工人尿砷超标的危险因素。     

冶炼工人尿形态砷与健康效应的关系

目的通过冶炼工人尿总砷(TAs)和尿形态砷水平测定分析,探讨体内砷代谢产物与某些健康效应的关系。方法选择2家有色金属冶炼厂(铅冶炼、锡冶炼各1家)工人(暴露组)137人为研究对象,其中铅冶炼组40人,锡冶炼组97人。不接触砷的小学教师42人为对照组。测定尿总砷及尿形态砷,并进行健康监护。还检测了作业场所环境中砷化合物浓度。结果锡、铅两冶炼厂岗位平均砷化合物浓度分别为0.52和0.20mg/m3,超过职业卫生标准。暴露组的TAs、二甲基砷酸盐(DMA)含量与对照组比较,差异有统计学意义(P0.01)。暴露组及对照组尿中形态砷均以DMA为主,占形态砷含量的90%以上。车间空气中的砷尘浓度与工人尿总砷、DMA呈正相关关系。随着总砷、DMA浓度的升高,转氨酶升高、血红细胞下降、肝脏B超及心电图异常检出率也呈升高趋势。结论随着接触砷浓度增高,工人体内总砷、DMA随之增高,砷及形态砷(特别是DMA)对肝脏、心脏、红细胞等影响作用越明显。     

长期高砷暴露人群砷甲基化与皮肤损害关系的研究

目的探讨长期高砷暴露人群砷代谢差异与砷致皮肤损害之间的关系。方法随机选取某砷污染村庄常住居民327名,进行问卷调查和体格检查。二乙基二硫代氨基甲酸银比色法检测发总砷含量,离子色谱氢化物发生原子荧光法测定尿中四种砷代谢形态。结果发砷含量总体较高,但不同程度皮肤损害的4组间发砷含量差异无显著性;尿中DMA和MMA浓度随着年龄增加有上升的趋势,且与皮肤损害程度呈显著正相关,而无机砷浓度与皮肤损害未见显著相关;重度组人群尿中MMA相对比例显著高于其它3组,而重度组DMA/MMA比值显著低于对照组和轻度组;MMA比例与皮肤损害程度呈显著正相关,DMA/MMA比值与皮肤损害程度呈显著负相关;男性对砷的蓄积能力高于女性,但对砷的甲基化能力低于女性;40岁以上人群对砷的甲基化能力高于40岁以下成人;吸烟者和饮酒者对砷的甲基化代谢水平分别低于非吸烟者和非饮酒者。结论砷在人体内的甲基化代谢水平受性别、年龄、吸烟和饮酒等多因素影响;砷致皮肤损伤程度与砷在体内的甲基化程度有关。     

Urinary arsenic metabolites of subjects exposed to elevated arsenic present in coal in Shaanxi Province, China

In contrast to arsenic (As) poisoning caused by naturally occurring inorganic arsenic-contaminated water consumption, coal arsenic poisoning (CAP) induced by elevated arsenic exposure from coal combustion has rarely been reported. In this study, the concentrations and distributions of urinary arsenic metabolites in 57 volunteers (36 subjects with skin lesions and 21 subjects without skin lesions), who had been exposed to elevated levels of arsenic present in coal in Changshapu village in the south of Shaanxi Province (China), were reported. The urinary arsenic species, including inorganic arsenic (iAs) [arsenite (iAsIII) and arsenate (iAsV)], monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV), were determined by high-performance liquid chromatography (HPLC) combined with inductively coupled plasma mass spectroscopy (ICP-MS). The relative distributions of arsenic species, the primary methylation index (PMI=MMAV/iAs) and the secondary methylation index (SMI=DMAV/MMAV) were calculated to assess the metabolism of arsenic. Subjects with skin lesions had a higher concentration of urinary arsenic and a lower arsenic methylation capability than subjects without skin lesions. Women had a significantly higher methylation capability of arsenic than men, as defined by a higher percent DMAV and SMI in urine among women, which was the one possible interpretation of women with a higher concentration of urinary arsenic but lower susceptibility to skin lesions. The findings suggested that not only the dose of arsenic exposure but also the arsenic methylation capability have an impact on the individual susceptibility to skin lesions induced by coal arsenic exposure.     

砷化氢作业工人尿中砷含量相关因素的多元线性回归分析

目的分析寻找砷化氢作业工人的尿中砷含量的主要影响因素,为预防砷化氢中毒提供参考。方法收集132例砷化氢作业工人的尿砷水平及其相关因素的详细资料,采用多元逐步回归和多元线性回归的方法进行统计分析。结果获得回归方程lgY=0.551 D1+0.281 D2+0.665 X7+0.059 X8+0.005 X3-2.279,决定系数调整R2=0.885,其中D1,D2代表工种的2个虚拟变量,X7代表砷化氢浓度,X8代表自觉症状,X3代表年龄,标准化偏回归系数分别为0.569,0.268,0.624,0.056,0.054。结论回归方程表明砷化氢作业工人尿砷的主要影响因素为工种、砷化氢浓度,提示预防砷化氢中毒要做好高危工种工人的防护,控制好作业场所空气中砷化氢的浓度。     

柳州市正常人群尿砷的正常参考值

目的探讨柳州市无砷接触史的健康成年尿砷的正常参考值上限。方法收集装配公司、机械制造公司、制糖公司等职工及职业技校师生中无砷接触史、经健康检查正常的305份成人的一次性尿样;以某金属治炼有限公司等单位的砷化氢作业接触者作对照组;以原子荧光分光光度法测定尿砷含量。结果正常人群尿砷含量95%上限值为0.104mg/L;305名男女无砷接触史的健康成人尿砷含量基本接近,冶炼厂砷化氢作业接触者(132人)尿砷含量与正常人尿砷比较,差异有统计学意义(P0.01)。结论根据调查结果,建议柳州市尿砷正常参考值上限为0.11mg/L。     

某冶炼企业作业工人尿砷和血铅检测及临床观察

目的通过检测企业职工的尿砷和血铅含量及对超标者进行临床观察、治疗,了解工作环境中砷、铅对职工身体健康状况的影响。方法采集某冶炼厂一线作业工人的169份尿液和血液,用湿法消解-原子荧光法和石墨炉原子吸收光谱法分别进行尿砷和血铅含量捡测。结果 169名工人中,有25例尿中砷含量增高,45例血中铅含量增高,其中14例尿砷和血铅检测结果同时增高,分别占体检人数的14.79%、26.63%、8.28%。且男性血铅异常百分率明显高于女性(P0.01)。部分砷、铅超标工人出现头昏、腰背酸痛、全身乏力、精神睡眠差、胃肠消化道症状及血、尿常规、肝功异常。结论该企业生产环境中砷、铅已对职工身体健康造成一定影响,应加强作业环境监测,改善劳动条件,提高工人的职业防护意识。     

砷职业暴露员工尿中价态砷含量与健康相关因素的分析

目的通过职业砷暴露水平与尿中总砷（TAs）和尿价态砷含量的测定,初步分析体内砷代谢产物（价态砷）与健康相关生化指标之间的关联性。方法选择2家有色金属冶炼企业砷暴露作业工人（暴露组）137人,其中砷暴露锡冶炼组97人、铅冶炼组40人。对照组为无砷接触者42人。暴露组及对照组均进行健康监护及收集晨尿,行尿中TAs及尿价态砷含量测定,并检测作业场所空气中砷及其化学物浓度,进行尿中TAs、价态砷与健康相关因素之间的相关分析。结果两厂砷暴露工作环境空气中含TAs浓度（中位数）为0．30（0．01—1．35）mg／m3。其中铅冶炼厂砷浓度为0．46（0．01—1．03）mg／m3,锡冶炼厂砷浓度为0．26（0．06—1．35）mg／m3。暴露组的TAs、二甲苯呻酸监（DMA）含量与对照组比较,差异有统计学意义（P〈0．01）;暴露组TAs与DMA之间呈正相关（相关系数r=0．693,P〈0．01）;DMA与丙氨酸转氨酶、天冬氨酸转氨酶（ALT、AST）之间呈正相关关系（r=0．148,P〈0．05、r=0．268,P〈0．01）、与血常规RBC、HGB呈负相关（r=-0．165,P=0．038、r=-0．149,P=0．015）。结论砷暴露作业工人在无机砷较高浓度下作业,体内无机砷甲基化后主要的代谢产物为DMA与MMA,且价态砷特别是DMA与TAs、ALT、AST呈正相关、与RBC、HGB呈负相关,说明DMA对肝细胞、红细胞存在一定损害作用。     

Urinary arsenic species, toenail arsenic, and arsenic intake estimates in a Michigan population with low levels of arsenic in drinking water

The large disparity between arsenic concentrations in drinking water and urine remains unexplained. This study aims to evaluate predictors of urinary arsenic in a population exposed to low concentrations (≤50?μg/l) of arsenic in drinking water. Urine and drinking water samples were collected from a subsample (n=343) of a population enrolled in a bladder cancer case-control study in southeastern Michigan. Total arsenic in water and arsenic species in urine were determined using ICP-MS: arsenobetaine (AsB), arsenite (As[III]), arsenate (As[V]), methylarsenic acid (MMA[V]), and dimethylarsenic acid (DMA[V]). The sum of As[III], As[V], MMA[V], and DMA[V] was denoted as SumAs. Dietary information was obtained through a self-reported food intake questionnaire. Log(10)-transformed drinking water arsenic concentration at home was a significant (P<0.0001) predictor of SumAs (R(2)=0.18). Associations improved (R(2)=0.29, P<0.0001) when individuals with less than 1?μg/l of arsenic in drinking water were removed and further improved when analyses were applied to individuals who consumed amounts of home drinking water above the median volume (R(2)=0.40, P<0.0001). A separate analysis indicated that AsB and DMA[V] were significantly correlated with fish and shellfish consumption, which may suggest that seafood intake influences DMA[V] excretion. The Spearman correlation between arsenic concentration in toenails and SumAs was 0.36 and between arsenic concentration in toenails and arsenic concentration in water was 0.42. Results show that arsenic exposure from drinking water consumption is an important determinant of urinary arsenic concentrations, even in a population exposed to relatively low levels of arsenic in drinking water, and suggest that seafood intake may influence urinary DMA[V] concentrations.     

Arsenic methylation, GSTT1, GSTM1, GSTP1 polymorphisms, and skin lesions

OBJECTIVE: We investigated whether primary and secondary arsenic methylation ratios were associated with skin lesions and whether GSTT1, GSTP1, and GSTM1 polymorphisms modify these relationships. METHODS: A case-control study of 600 cases and 600 controls that were frequency matched on age and sex was conducted in Pabna, Bangladesh, in 2001-2002. Individual well water, urine, and blood samples were collected. Water arsenic concentration was determined using inductively coupled plasma mass spectrometry (ICP-MS). Urinary arsenic speciation was determined using high performance liquid chromatography hydride with generator atomic absorption spectrometry and ICP-MS. Genotyping was conducted using multiplex polymerase chain reaction and TaqMan. RESULTS: A 10-fold increase in primary methylation ratio [monomethylarsonic acid (MMA)/(arsenite + arsenate] was associated with a 1.50-fold increased risk of skin lesions (multivariate odds ratio = 1.50; 95% confidence interval, 1.00-2.26). We observed significant interaction on the multiplicative scale between GSTT1 wildtype and secondary methylation ratio [dimethylarsinic acid/MMA; likelihood ratio test (LRT), p = 0.01]. No significant interactions were observed for GSTM1 or GSTP1 or for primary methylation ratios. CONCLUSION: Our findings suggest that increasing primary methylation ratios are associated with an increase in risk of arsenic-related skin lesions. The interaction between GSTT1 wildtype and secondary methylation ratio modifies risk of skin lesions among arsenic-exposed individuals.     

Distribution of urinary selenium and arsenic among pregnant women exposed to arsenic in drinking water

Inorganic arsenic (In-As) is a well-known toxicant and carcinogen found naturally in surface and groundwater around the world. Exposure can cause skin lesions, adverse reproductive outcomes, and cancer. There are two main pathways of arsenic (As) metabolism in humans: the reduction reactions, and the oxidative methylation reactions, where methyl groups are attached to As compounds to form monomethylarsenate (MMA) and dimethylarsenate (DMA). MMA, DMA, and In-As are excreted in urine. Urinary levels of another metalloid, selenium (Se), have recently been shown to be associated with increased As excretion and altered metabolite distribution. This study investigates this association, using data collected in a larger prospective study of arsenic and reproductive effects in Chile. This analysis included 93 pregnant women from Antofagasta. Data on demographic, behavioral, and other characteristics were obtained via interviews conducted by trained midwives, and spot urine samples were analyzed for As and Se concentration using inductively coupled plasma-mass spectrometry (ICP-MS). Urinary Se levels were found to be correlated with urinary As levels in bivariate analysis (r = 0.68, P < 0.01). Multiple linear regression analyses revealed that higher urinary Se levels were associated with increased urinary As excretion, increased %DMA, and decreased %In-As. The results of this study suggest that in populations exposed to arsenic, Se intake may be correlated with urinary As excretion, and may alter As methylation.