Urinary arsenic metabolites in children and adults exposed to arsenic in drinking water in Inner Mongolia, China

BACKGROUND: We report the concentrations and distributions of urinary arsenic (As) metabolites in 233 residents exposed to 20, 90, or 160 microg/L inorganic arsenic (iAs) in drinking water from three villages in Hohhot, Inner Mongolia, China, that formed one control and two exposed groups. METHODS: We used hydride generation-atomic absorption spectrometry (HGAAS) to determine iAs, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA). RESULTS: The concentrations of each urinary As species in the two exposed groups were significantly higher than in the control group for both children and adults. Both children and adults in exposed groups had higher percent iAs and MMA and lower percent DMA, and low primary and secondary methylation indices (PMI and SMI, respectively) than those in the control group. However, children showed significant increases in percent DMA and the SMI as well as decreases in the percent MMA when the iAs exposure level increased from 90 to 160 microg/L. In addition, children in the two exposed groups showed lower percent MMA but higher percent DMA and higher SMI than adults in the same exposed group. No significant differences in As metabolite concentrations and distributions were found between males and females in each group. A significant correlation was also found in the SMI between 11 pairs of children and their mothers from the 160-microg/L-exposed group. CONCLUSIONS: Children had higher a capacity for secondary methylation of As than adults when exposed to the same concentrations of iAs in drinking water. Exposure to As may increase the capacity for methylation in children to some extent.     

高砷暴露致皮肤损伤人群尿砷代谢产物分析

目的 探讨高砷暴露致皮肤损伤人群尿砷代谢的特点.方法 应用氢化物发生.冷阱捕获.原子吸收分光光度法测定高砷暴露地Ⅸ(水砷浓度分别为0.21、0.24、0.36 mg/L)皮肤损伤组人群(77人)和未见皮肤损伤对照组人群(77人,性别、年龄1:1配比)尿中无机砷(iAs)、一甲基胂酸(MMA)和二甲基胂酸(DMA)含量.以iAs、MMA及DMA的总和表示总砷(tAs)水平;以iAs/tAs、MMMtAs和DMA/tAs分别计算iAs%、MMA%、DMA%;以(MMA+DMA)/tAs及DMM(MMA+DMA)分别计算一甲基化率(FMR)和二甲基化率(SMR)水平.结果 皮肤损伤组人群与对照组人群相比尿中各形态砷化合物及总砷含量差异无统计学意义(JD>0.05),而皮肤损伤组尿iAs%水平高于对照组,DMA%、FMR和SMR水平低于对照组差异均有统计学意义(P<0.05).皮肤损伤组人群中男性SMR水平显著低于女性,且尿中MMA%显著高于女性(P<0.05).结论 高砷暴露情况下,出现皮肤损伤症状的人群对砷的甲基化能力较低.

Abstract：

Objective To explore the characteristics of urine arsenic metabolism of people with skin lesion. Methods The levels of inorganic arsenic (iAs), monomethylated arsenic (MMA), dimethylated arsenic (DMA) in urine were detected with hydride generation-cold trap-atomic absorption spectroscopy among population exposed to higher levels of arsenide (0.24 ,0.36,0.21 mg/L), which consisted of skin lesion group(n=77) and non-skin lesion group (n=77,control group) in Apr.,2009 . Total arsenic (tAs) , iAs %, MMA%, DMA%, the first methylation ratio (FMR) and the secondary methylation ratio (SMR) were calculated as iAs + MMA+ DMA , iAs/tAs, MMA/tAs, DMA/tAs, (MMA + DMA)/ tAs and DMA/(MMA + DMA), respectively. Results No significant difference was observed in urinary concentrations of arsenic species and tAs between two groups (P>0.05), iAs% was much higher and the levels of FMR, SMR and DMA% were significantly lower in skin lesion group compared with the control (P<0.05). There were statistically significant differences in iAs% and SMR between males and females of the skin lesion group(P<0.05). Conclusion The arsenic methylation capacity of the persons with skin lesions is lower at high arsenic exposure.     

内蒙古不同浓度砷暴露人群尿砷代谢产物研究

目的 测定内蒙古地区饮用高砷水人群尿砷代谢产物，探讨不同人群砷代谢的特点。方法 采用氢化物发生原子吸收分光光度法检测尿中不同形态的砷代谢产物。结果 2个暴露组人群尿中无机砷（iAs，inorganic arserlic）、甲基砷（MMA，monomethylarsine）、二甲基砷（DMA．dimethylarsine）和总砷（TAs，total arserlic）均高于对照组（P〈0．05）；同样砷暴露水平下，尿中各形态砷含量及其相对比在不同性别问的差异均无统计学意义（P〉0．05），儿童DMA／MMA和DMA％高于成人（P〈0．05），MMA％低于成人（P〈0．05）；2个暴露组儿童、成人分别与对照组比较，暴露组MMA／ias、DMA／MMA、DMA／iAs、DMA％显降低（P〈0．05），而iAs％、MMA％显增高（P〈0．05）；高暴露组与低暴露组相比，儿童DMA／MMA、DMA／iAs、DMA％显增高（P〈0．05），iAs％、MMA％显降低（P〈0．05）。结论 相同砷暴露水平下，男女对砷的甲基化能力无差别，儿童二甲基化能力高于成人。高砷暴露可能降低人群对砷的生物甲基化能力。[编按]     

HPLC-ICP-MS speciation analysis of arsenic in urine of Japanese subjects without occupational exposure

The toxicity and carcinogenicity of arsenic depend on its species. Individuals living in Japan consume much seafood that contains high levels of organoarsenics. Speciation analysis of urinary arsenic is required to clarify the health risks of arsenic intake. There has been no report of urinary arsenic analysis in Japan using high performance liquid chromatography with inductively coupled plasma mass spectrometry (HPLC-ICP-MS). We performed speciation analysis of urinary arsenic for 210 Japanese male subjects without occupational exposure using HPLC-ICP-MS. The median values of urinary arsenics were as follows: sodium arsenite (AsIII), 3.5; sodium arsenate (AsV), 0.1; monomethylarsonic acid (MMA), 3.1; dimethylarsinic acid (DMA), 42.6; arsenobetaine (AsBe), 61.3; arsenocholine, trimethylarsine oxide, and unidentified arsenics (others), 5.2; and total arsenic (total As), 141.3 microgAs/l. The median creatinine-adjusted values were as follows: AsIII, 3.0; AsV, 0.1; MMA, 2.6; DMA, 35.9; AsBe, 52.1; others 3.5; and total As, 114.9 microgAs/g creatinine. Our findings indicate that DMA and AsBe levels in Japan are much higher than those found in Italian and American studies. It appears that the high levels of DMA and AsBe observed in Japan may be due in part to seafood intake. ACGIH and DFG set the BEI and BAT values for occupational arsenic exposure as 35 microgAs/l and 50 microgAs/l, respectively, using the sum of inorganic arsenic (iAs), MMA, and DMA. In the general Japanese population, the sums of these were above 50 microgAs/l in 115 (55%) samples. We therefore recommend excluding DMA concentration in monitoring of iAs exposure.     

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.     

饮水型砷暴露对人群甲基化代谢能力的影响

目的探讨饮水型砷暴露对人群甲基化代谢能力的影响。方法以带有砷化物预处理装置的原子吸收分光光度计测定砷暴露人群及无砷暴露对照人群血、尿中无机砷(iAs)、甲基胂(MMA)、二甲基胂(DMA)含量。以iAs、MMA及DMA的总和表示总胂(tAs)水平;以(MMA+DMA)/tAs及DMA/(MMA+DMA)分别计算一甲基化率(PMI)和二甲基化率(SMI)水平。结果砷暴露人群血中iAs、MMA、DMA、tAs及PMI水平均显著高于相应对照人群的水平,而SMI水平显著低于对照人群。尿中MMA水平分别与血中PMI及SMI水平呈显著正相关(r=0.419,P<0.01)及负相关(r=-0.326,P<0.05)。暴露组和对照组血中各种砷化物水平及甲基化率水平在男女间差异无显著性。结论砷暴露人群与无砷暴露人群相比甲基化率有差异,PMI显著增高,SMI显著降低。人群甲基化率无显著性别差异。     

Arsenic speciation analysis of urine samples from individuals living in an arsenic-contaminated area in Bangladesh

Objectives

Chronic inorganic arsenic (iAs) exposure currently affects tens of millions of people worldwide. To accurately determine the proportion of urinary arsenic metabolites in residents continuously exposed to iAs, we performed arsenic speciation analysis of the urine of these individuals and determined whether a correlation exists between the concentration of iAs in drinking water and the urinary arsenic species content.

Methods

The subjects were 165 married couples who had lived in the Pabna District in Bangladesh for more than 5 years. Arsenic species were measured using high-performance liquid chromatography and inductively coupled plasma mass spectrometry.

Results

The median iAs concentration in drinking water was 55 μgAs/L (range <0.5–332 μgAs/L). Speciation analysis revealed the presence of arsenite, arsenate, monomethylarsonic acid (MMA), and dimethylarsinic acid in urine samples with medians (range) of 16.8 (7.7–32.3), 1.8 (<0.5–3.3), 13.7 (5.6–25.0), and 88.6 μgAs/L (47.9–153.4 μgAs/L), respectively. No arsenobetaine or arsenocholine was detected. The concentrations of the 4 urinary arsenic species were significantly and linearly related to each other. The urinary concentrations of total arsenic and each species were significantly correlated with the iAs concentration of drinking water.

Conclusions

All urinary arsenic species are well correlated with each other and with iAs in drinking water. The most significant linear relationship existed between the iAs concentration in drinking water and urinary iAs + MMA concentration. From these results, combined with the effects of seafood ingestion, the best biomarker of iAs exposure is urinary iAs + MMA concentration.     

Comparison of different medical cases in urinary arsenic speciation by fast HPLC-ICP-MS

The inorganic arsenic species As(III), As(V) and the organic species methylarsonate (MMA(V)), dimethylarsinate (DMA(V)) and arsenobetaine (AsB) were determined in human urine by a fast anion exchange HPLC-ICP-MS method, which was developed for clinical laboratories with high sample throughput. This paper compares typical chromatograms of the arsenic species in urine samples collected in different medical cases, for example, for the non-exposed population, for environmentally (plant protectants) and occupationally (glass manufacture) exposed persons, for a person after a failed suicide attempt with As2O3 and for persons before and after administration of the antidot sodium 2,3-dimercapto-1-propane-sulfonate (DMPS). Concentration data of the urinary As species for the non-exposed German population (n=82) are compared with the concentrations before and after administration of DMPS (n=37). For the non-exposed group the toxicologically relevant As in urine consists of 81% DMA(V), 10% MMA(V) and 9% inorganic As. However, a few hours after an acute intoxication with inorganic As this distribution changes dramatically and As(III) and As(V) are predominantly found in urine. After treatment with DMPS the total As concentration increases significantly and mainly MMA(V) and As(III) were found in urine samples.     

A Population-based Case–Control Study of Urinary Arsenic Species and Squamous Cell Carcinoma in New Hampshire,USA

Background: Chronic high arsenic exposure is associated with squamous cell carcinoma (SCC) of the skin, and inorganic arsenic (iAs) metabolites may play an important role in this association. However, little is known about the carcinogenicity of arsenic at levels commonly observed in the United States.Objective: We estimated associations between total urinary arsenic and arsenic species and SCC in a U.S. population.Methods: We conducted a population-based case–control SCC study (470 cases, 447 controls) in a U.S. region with moderate arsenic exposure through private well water and diet. We measured urinary iAs, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA), and summed these arsenic species (ΣAs). Because seafood contains arsenolipids and arsenosugars that metabolize into DMA through alternate pathways, participants who reported seafood consumption within 2 days before urine collection were excluded from the analyses.Results: In adjusted logistic regression analyses (323 cases, 319 controls), the SCC odds ratio (OR) was 1.37 for each ln-transformed microgram per liter increase in ln-transformed ΣAs concentration [ln(ΣAs)] (95% CI: 1.04, 1.80). Urinary ln(MMA) and ln(DMA) also were positively associated with SCC (OR = 1.34; 95% CI: 1.04, 1.71 and OR = 1.34; 95% CI: 1.03, 1.74, respectively). A similar trend was observed for ln(iAs) (OR = 1.20; 95% CI: 0.97, 1.49). Percent iAs, MMA, and DMA were not associated with SCC.Conclusions: These results suggest that arsenic exposure at levels common in the United States relates to SCC and that arsenic metabolism ability does not modify the association.Citation: Gilbert-Diamond D, Li Z, Perry AE, Spencer SK, Gandolfi AJ, Karagas MR. 2013. A population-based case–control study of urinary arsenic species and squamous cell carcinoma in New Hampshire, USA. Environ Health Perspect 121:1154–1160; http://dx.doi.org/10.1289/ehp.1206178     

GSTT1和GSTM1基因多态性与人体砷甲基化代谢水平关系探讨

目的探讨GSTT1、GSTM1基因多态性与人体砷甲基化代谢水平之间的关系。方法选择某工业性砷污染区的247名成年常住居民为研究对象。采用多重PCR法检测GSTM1和GSTT1基因多态性。离子色谱氢化物发生原子荧光法(IC-HG-AFS)测定尿中无机砷(iAs)、一甲基胂酸(MMA)和二甲基胂酸(DMA)。结果GSTT1缺失基因型人群与GSTT1非缺失基因型人群尿中iAs比例、DMA比例和MMA比例相比较,差异均无统计学意义(P>0.05)。GSTM1缺失基因型人群与GSTM1非缺失基因型人群尿中iAs比例、DMA比例和MMA比例相比较,差异均无统计学意义(P>0.05)。四组不同GSTT1和GSTM1联合基因型人群尿中iAs比例、DMA比例和MMA比例相比较,四组间差异也均无统计学意义(P>0.05)。结论本研究未发现GSTT1、GSTM1基因多态性与砷代谢水平之间存在显著关联。     

Association between arsenic exposure from a coal-burning power plant and urinary arsenic concentrations in Prievidza District,Slovakia

To assess the arsenic exposure of a population living in the vicinity of a coal-burning power plant with high arsenic emission in the Prievidza District, Slovakia, 548 spot urine samples were speciated for inorganic As (Asinorg), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and their sum (Assum). The urine samples were collected from the population of a case-control study on nonmelanoma skin cancer (NMSC). A total of 411 samples with complete As speciations and sufficient urine quality and without fish consumption were used for statistical analysis. Although current environmental As exposure and urinary As concentrations were low (median As in soil within 5 km distance to the power plant, 41 micro g/g; median urinary Assum, 5.8 microg/L), there was a significant but weak association between As in soil and urinary Assum(r = 0.21, p < 0.01). We performed a multivariate regression analysis to calculate adjusted regression coefficients for environmental As exposure and other determinants of urinary As. Persons living in the vicinity of the plant had 27% higher Assum values (p < 0.01), based on elevated concentrations of the methylated species. A 32% increase of MMA occurred among subjects who consumed homegrown food (p < 0.001). NMSC cases had significantly higher levels of Assum, DMA, and Asinorg. The methylation index Asinorg/(MMA + DMA) was about 20% lower among cases (p < 0.05) and in men (p < 0.05) compared with controls and females, respectively.     

Urinary Arsenic Speciation and its Correlation with 8-OHdG in Chinese Residents Exposed to Arsenic Through Coal Burning

In contrast to arsenicosis caused by consumption of water contaminated by naturally occurring inorganic arsenic, human exposure to this metalloid through coal burning has been rarely reported. In this study, arsenic speciation and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels in urine were determined in the Chinese residents exposed to arsenic through coal burning in Guizhou, China, an epidemic area of chronic arsenic poisoning caused by coal burning. The urinary concentrations of inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and total arsenic (tAs) of high-arsenic exposed subjects were significantly higher than those of low-arsenic exposed residents. A biomarker of oxidative DNA damage, urinary 8-OHdG level was significantly higher in high-arsenic exposed subjects than that of low exposed. Significant positive correlations were found between 8-OHdG levels and concentrations of iAs, MMA, DMA and tAs, respectively. In addition, a significant negative correlation was observed between 8-OHdG levels and the secondary methylation ratio (DMA/(MMA + DMA)). The results suggest that chronic arsenic exposure through burning coal rich in arsenic is associated with oxidative DNA damages, and that secondary methylation capacity is potentially related to the susceptibility of individuals to oxidative DNA damage induced by arsenic exposure through coal burning in domestic living.     

砷暴露母子砷代谢特点及DNA损伤差异

目的通过尿中各种形态砷水平，探讨高砷暴露下儿童砷代谢特点；测定尿中8-羟基脱氧鸟苷（8-O-HdG）水平。初步探讨砷暴露对儿童DNA的损伤情况；并比较砷暴露对儿童与成人的不同影响。方法以氢化物发生．冷原子捕获．原子吸收分光光度法测定尿中各种砷化物的含量；以试剂盒法测定尿8-OHdG水平。结果砷暴露组妇女和儿童尿中无机砷（iAs）、二甲基砷（MMA）、甲基砷（DMA）及总砷（tAs）水平均显著高于对照组；砷暴露母子间，子女尿中iAs、DMA、tAs及DMA／tAs水平显著高于其母亲，而MMA／（MMA＋DMA）显著低于其母亲。母子间8-O-HdG水平差异无统计学意义。结论高砷暴露下，儿童二甲基化能力高于成人，DNA氧化损伤与成人相比不明显。     

外源性蛋氨酸对饮水砷暴露雌性小鼠体内砷形态分布的影响

目的 探讨外源性蛋氨酸(methionine,Met)对饮水砷暴露小鼠体内不同组织器官砷形态分布的影响.方法 将健康清洁级雌性昆明小鼠40只,随机分为对照组、单纯砷染毒组及低、中、高剂量Met与砷联合染毒组,每组8只.除对照组小鼠饮蒸馏水外,其余各组小鼠以自由饮水方式饮含50mg/L亚砷酸钠的水,连续染毒4周.在染毒的第4周,低、中、高剂量Met与砷联合染毒组小鼠分别被腹腔注射100、200、400 mg/kg的Met溶液,对照组和单纯砷染毒组小鼠被腹腔注射生理盐水,连续注射7 d.末次注射24 h后,处死小鼠,快速取血,分离肝和脑组织,分别检测无机砷(iAs)、一甲基胂酸(MMA)和二甲基胂酸(DMA)含量,并计算各组织中总砷含鼍(TAs)及砷一甲基化率(primary methylation ratio,PMR)和二甲基化率(secondary methylation ratio,SMR).结果 单纯砷染毒组和高、中、低剂量Met与砷联合染毒组小鼠肝、脑组织及全血中iAs、MMA、DMA和TAs含量均高于对照组,差异有统计学意义(P<0.05).与单纯砷染毒组比较,中、高剂量Met与砷联合染毒组小鼠肝组织中DMA含量和PMR较高,差异有统计学意义(P<0.05).与单纯砷染毒组比较,各剂量Met与砷联合染毒组小鼠全血中iAs、MMA和TAs含量均下降,差异有统计学意义(P<0.05).各剂量Met与砷联合染毒组小鼠脑组织中DMA和TAs含量低于单纯砷染毒组,差异有统计学意义(P<0.05).结论 外源性Met 对小鼠体内砷甲基化代谢具有促进作用,并可加速体内砷化物的排泄,从而减少血液和脑组织中的砷负荷.     

Study on the relationship between GSTM1, GSTT1 gene polymorphisms and arsenic methylation level

OBJECTIVE: To investigate the relationship between genetic polymorphisms of GSTT1, GSTM1 and arsenic methylation level. METHODS: 247 residents in an industrial arsenic polluted village were randomly selected as subjects. The genetic polymorphisms of GSTM1 and GSTT1 were detected by multiple PCR method. Urinary inorganic arsenic (iAs), monomethylarsenic acid (MMA) and dimethylarsenic acid (DMA) concentrations were determined by ion chromatogram combined with HG-AFS. RESULTS: No significant differences in the relative proportion of urinary iAs, MMA and DMA were observed between the individuals with GSTT1 positive genotype and the individuals with GSTT1 null genotype. No significant differences in the relative proportion of urinary iAs, MMA and DMA were observed between the individuals with GSTM1 positive genotype and the individuals with GSTM1 null genotype. And no significant differences in the relative proportion of urinary iAs, MMA and DMA was observed among the individuals with different GSTM1 and GSTT1 associated genotype. CONCLUSION: The polymorphisms of GSTT1 and GSTM1 were not associated with arsenic metabolism level in the studied population.     

Assessing the measurement precision of various arsenic forms and arsenic exposure in the National Human Exposure Assessment Survey (NHEXAS)

Archived samples collected from 1995 to 1997 in the National Human Exposure Assessment Survey (NHEXAS) in U.S. Environmental Protection Agency Region 5 (R5) and the Children's Study (CS) in Minnesota were analyzed for total arsenic, arsenate [As(V)], arsenite, dimethyl arsenic acid (DMA), monomethyl arsenic acid (MMA), arsenobetaine (AsB), and arsenocholine. Samples for the CS included drinking water, urine, hair, and dust; both studies included food (duplicate plate, composited 4-day food samples from participants). Except for AsB and As(V), the levels for As species measured in the food and drinking water samples were very low or nonexistent. The analytical methods used for measuring As species were sensitive to < 1 ppb. During the analysis of food and drinking water samples, chromatographic peaks appeared that contained As, but they did not correspond to those being quantified. Thus, in some samples, the sum of the individual As species levels was less than the total As level measured because the unknown forms of As were not quantified. On the other hand, total As was detectable in almost all samples (> 90%) except for hair (47%), indicating that the analytical method was sufficiently sensitive. Population distributions of As concentrations measured in drinking water, food (duplicate plate), dust, urine, and hair were estimated. Exposures to total As in food for children in the CS were about twice as high as in the general R5 population (medians of 17.5 ppb and 7.72 ppb, respectively). In addition, AsB was the most frequently detected form of As in food eaten by the participants, while As(V) was only rarely detected. Thus, the predominant dietary exposure was from an organic form of As. The major form of As in drinking water was As(V). Spearman (rank) correlations and Pearson (log-concentration scale) correlations between the biomarkers (urine, hair) and the other measures (food, drinking water, dust) and urine versus hair were performed. In the NHEXAS CS, total As and AsB in the food eaten were significantly correlated with their levels in urine. Also, levels of As(V) in drinking water correlated with DMA and MMA in urine. Arsenic levels in dust did not show a relationship with urine or hair levels, and no relationship was observed for food, drinking water, and dust with hair. Urine samples were collected on days 3, 5, and 7 of participants' monitoring periods. Total As levels in urine were significantly associated across the three pairwise combinations--i.e., day 3 versus day 5, day 3 versus day 7, and day 5 versus day 7. Because the half-life of As in the body is approximately 3 days, this suggests that some exposure occurred continually from day to day. This trend was also observed for AsB, suggesting that food is primarily responsible for the continual exposure. DMA and MMA in urine were also significantly correlated but not in all combinations.     

母体砷暴露仔鼠肝脑组织中砷形态分布

目的探索小鼠早期砷暴露后,砷化物在肝、脑组织中的代谢与分布情况。方法采用氢化物发生-超低温捕集-原子吸收分光光度法测定母鼠和仔鼠肝和脑组织中无机砷(iAs)、一甲基胂(MMA)及二甲基胂(DMA)含量。结果各组母鼠肝组织中iAs、MMA和DMA含量及脑组织中iAs和DMA含量随饮水中砷浓度增加而增加;小鼠在生后15d肝组织中iAs含量增加,MMA含量在生后21 d增加;生后10、15、21 d,高砷组DMA含量分别为(0.020±0.005)、(0.031±0.012)、(0.239±0.076)μg/g,生后21 d DMA含量高于新生仔鼠和生后35 d仔鼠。高砷组脑组织iAs含量在仔鼠生后21 d达最高水平(0.088±0.042)μg/g;MMA在早期发育阶段未检测到;DMA平均水平在生后10d和15 d最低。结论乳房屏障可以有效阻止iAs和DMA进入母鼠乳汁中,成熟血脑屏障能够有效阻止iAs进入脑组织。     

人体入紫菜后尿中砷化物的排泄规律研究

目的 观察正常人摄人紫菜后,尿中不同形态砷化物随时间的排泄规律.方法 收集24名受试者(14名男性,10名女性)食人紫菜后72 h内不同时点的尿液,采用高效液相色谱.氢化物发生.原子荧光分光光度法(HPLC-HG-APS)检测尿中砷代谢产物的形态与浓度.结果 在食用紫菜后72 h内,与食用紫菜前比较,男性除第1和48 h外,尿中iAs浓度均显著增高(P<0.05);除第1和12 h外,尿中一甲基胂酸(MMA)浓度显著增高(P<0.05);第1～72 h尿中二甲基胂酸(DMA)浓度显著增高(P<0.05);女性受试者食用紫菜后,除第3、5和48 h外,尿中iAs浓度明显增高(P<0.05);除第5和12 h,尿中MMA浓度均显著增高(P<0.05);第1～72 h尿中DMA浓度均有显著增高(P<0.05).食用紫菜后,女性尿中DMA浓度显著高于男性.结论 摄入相同剂量紫菜后女性尿中DMA浓度显著高于男性,并且DMA浓度随时问先升高后降低.

Abstract：

Objective To know the effects of laver intake on arsenic species in urine of people, and investigate the characteristics of arsenic metabolism. Methods The urine samples were collected from 24 subjects who had laver available on markets, arsenic species in urine samples were detected with hydride generation atomic fluorescence spectroscopy. Results There was a significant increase of urinary iAs seventy-two hours after laver intake except one and forty-eight hours, increase of MMA seventy-two hours after laver intake except one and twelve hours, and increase of DMA from the first hour to the 72nd hour in male group. There was a significant increase in the urinary iAs seventy-two hours after laver intake except three, five and forty-eight hours, increase of MMA seventy-two hours after laver intake except five and twelve hours, increase of DMA from one to seventy-two hours after laver intake in female group. Conclusion The urinary concentration of DMA is significantly higher in female group compared with male group after laver intake in the same weight and urinary DMA increases in the beginning, after that decreases gradually.     

Profile of urinary arsenic metabolites during pregnancy

Chronic exposure to inorganic arsenic (In-As) from drinking water is associated with different health effects, including skin, lung, bladder, and kidney cancer as well as vascular and possibly reproductive effects. In-As is metabolized through the process of methylation, resulting in the production and excretion of methylated species, mainly monomethylarsenate (MMA) and dimethylarsenate (DMA). Because a large percentage of the dose is excreted in urine, the distribution of urinary In-As, MMA, and DMA is considered a useful indicator of methylation patterns in human populations. Several factors affect these patterns, including sex and exposure level. In this study, we investigated the profile of urinary In-As, MMA, and DMA of pregnant women. Periodic urine samples were collected from early to late pregnancy among 29 pregnant women living in Antofagasta, Chile, who drank tap water containing 40 micro g/L In-As. The total urinary arsenic across four sampling periods increased with increasing weeks of gestation, from an initial mean value of 36.1 to a final value of 54.3 micro g/L. This increase was mainly due to an increase in DMA, resulting in lower percentages of In-As and MMA and a higher percentage of DMA. Our findings indicate that among women exposed to moderate arsenic from drinking water during pregnancy, changes occur in the pattern of urinary arsenic excretion and metabolite distribution. The toxicologic significance of this is not clear, given recent evidence suggesting that intermediate methylated species may be highly toxic. Nevertheless, this study suggests that arsenic metabolism changes throughout the course of pregnancy, which in turn may have toxicologic effects on the developing fetus. Key words: arsenic, arsenic metabolism, arsenic methylation, Chile, pregnancy, urinary arsenic.     

Urinary trivalent methylated arsenic species in a population chronically exposed to inorganic arsenic

Chronic exposure to inorganic arsenic (iAs) has been associated with increased risk of various forms of cancer and of noncancerous diseases. Metabolic conversions of iAs that yield highly toxic and genotoxic methylarsonite (MAsIII) and dimethylarsinite (DMAsIII) may play a significant role in determining the extent and character of toxic and cancer-promoting effects of iAs exposure. In this study we examined the relationship between urinary profiles of MAsIII and DMAsIII and skin lesion markers of iAs toxicity in individuals exposed to iAs in drinking water. The study subjects were recruited among the residents of an endemic region of central Mexico. Drinking-water reservoirs in this region are heavily contaminated with iAs. Previous studies carried out in the local populations have found an increased incidence of pathologies, primarily skin lesions, that are characteristic of arseniasis. The goal of this study was to investigate the urinary profiles for the trivalent and pentavalent As metabolites in both high- and low-iAs-exposed subjects. Notably, methylated trivalent arsenicals were detected in 98% of analyzed urine samples. On average, the major metabolite, DMAsIII, represented 49% of total urinary As, followed by DMAsV (23.7%), iAsV (8.6%), iAsIII (8.5%), MAsIII (7.4%), and MAsV (2.8%). More important, the average MAsIII concentration was significantly higher in the urine of exposed individuals with skin lesions compared with those who drank iAs-contaminated water but had no skin lesions. These data suggest that urinary levels of MAsIII, the most toxic species among identified metabolites of iAs, may serve as an indicator to identify individuals with increased susceptibility to toxic and cancer-promoting effects of arseniasis.