Urinary Arsenic Levels Research Articles

Arsenic exposure and tobacco consumption: Biomarkers and risk assessment

Arsenic is measurable in tobacco and cigarette mainstream smoke (MSS). Whether arsenic has an independent role in diseases associated with tobacco consumption is not known. Epidemiology and biomonitoring data and probabilistic risk assessment (PRA) methods were used to investigate this potential association. Analysis of data from the National Health and Nutrition Examination Survey (NHANES) showed that urine arsenic concentrations in tobacco consumers were not different or were lower than levels in non-consumers of tobacco. Additionally, urine arsenic levels from NHANES tobacco consumers were five-times or more lower than levels reported in epidemiology studies to be associated with adverse health effects. Results of PRA indicated that mean non-cancer hazard estimates and mean incremental lifetime cancer risk estimates were within accepted ranges. Taken together, these results suggest that arsenic may not be independently associated with tobacco consumption or diseases related to tobacco consumption.

Urinary arsenic levels in the French adult population: The French National Nutrition and Health Study, 2006–2007

The French Nutrition and Health Survey (ENNS) was conducted to describe dietary intakes, nutritional status, physical activity, and levels of various biomarkers for environmental chemicals (heavy metals and pesticides) in the French population (adults aged 18–74years and children aged 3–17years living in continental France in 2006–2007). The aim of this paper was to describe the distributions of total arsenic and the sum of iAs+MMA+DMA in the general adult population, and to present their main risk factors.In the arsenic study, 1500 and 1515 adults (requested to avoid seafood intake in the previous 3days preceding urine collection) were included respectively for the analysis of the sum of inorganic arsenic (iAs) and its two metabolites, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), and for the total arsenic. Results were presented as geometric means and selected percentiles of urinary arsenic concentrations (μg/L) and creatinine-adjusted urinary arsenic (μg/g of creatinine) for total arsenic, and the sum of inorganic arsenic and metabolites (iAs+MMA+DMA). The geometric mean concentration of the sum of iAs+MMA+DMA in the adult population living in France was 3.34μg/g of creatinine [3.23–3.45] (3.75μg/L [3.61–3.90]) with a 95th percentile of 8.9μg/g of creatinine (10.68μg/L). The geometric mean concentration of total arsenic was 11.96μg/g of creatinine [11.41–12.53] (13.42μg/L [12.77–14.09]) with a 95th percentile of 61.29μg/g of creatinine (72.75μg/L).Urinary concentrations of total arsenic and iAS+MMA+DMA were influenced by sociodemographic and economic factors, and by risk factors such as consumption of seafood products and of wine. In our study, covariate-adjusted geometric means demonstrated several slight differences, due to consumption of fish, shellfish/crustaceans or wine.This study provides the first reference value for arsenic in a representative sample of the French population not particularly exposed to high levels of arsenic (10μg/g of creatinine). It shows that urinary arsenic concentrations in the French adult population (in particular concentrations of iAs+MMA+DMA) were relatively low compared with foreign data.

Altered Arsenic Disposition in Experimental Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is represented by a spectrum of liver pathologies ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). Liver damage sustained in the progressive stages of NAFLD may alter the ability of the liver to properly metabolize and eliminate xenobiotics. The purpose of the current study was to determine whether NAFLD alters the disposition of the environmental toxicant arsenic. C57BL/6 mice were fed either a high-fat or a methionine-choline-deficient diet to model simple steatosis and NASH, respectively. At the conclusion of the dietary regimen, all mice were given a single oral dose of either sodium arsenate or arsenic trioxide. Mice with NASH excreted significantly higher levels of total arsenic in urine (24 h) compared with controls. Total arsenic in the liver and kidneys of NASH mice was not altered; however, NASH liver retained significantly higher levels of the monomethyl arsenic metabolite, whereas dimethyl arsenic was retained significantly less in the kidneys of NASH mice. NASH mice had significantly higher levels of the more toxic trivalent form in their urine, whereas the pentavalent form was preferentially retained in the liver of NASH mice. Moreover, hepatic protein expression of the arsenic biotransformation enzyme arsenic (3+ oxidation state) methyltransferase was not altered in NASH animals, whereas protein expression of the membrane transporter multidrug resistance-associated protein 1 was increased, implicating cellular transport rather than biotransformation as a possible mechanism. These results suggest that NASH alters the disposition of arsenical species, which may have significant implications on the overall toxicity associated with arsenic in NASH.

Effect of fluoride exposure on the intelligence of school children in Madhya Pradesh, India.

Objective:To assess the relationship between exposure to different drinking water fluoride levels and children's intelligence in Madhya Pradesh state, India.Materials and Methods:This cross-sectional study was conducted among 12-year-old school children of Madhya Pradesh state, India. The children were selected from low (< 1.5 parts per million) and high (≥1.5 parts per million) fluoride areas. A questionnaire was used to collect information on the children's personal characteristics, residential history, medical history, educational level of the head of the family, and socioeconomic status of the family. Levels of lead, arsenic, and iodine in the urine and the levels of fluoride in the water and urine were analyzed. The children's intelligence was measured using Raven's Standard Progressive Matrices. Data analysis was done using the chi-square, one way analysis of variance, simple linear regression, and multiple linear regression tests. P value <0.05 was considered statistically significant.Results:Differences in participant's sociodemographic characteristics, urinary iodine, urinary lead, and urinary arsenic levels were statistically not significant (P>0.05). However, a statistically significant difference was observed in the urinary fluoride levels (P 0.000). Reduction in intelligence was observed with an increased water fluoride level (P 0.000). The urinary fluoride level was a significant predictor for intelligence (P 0.000).Conclusion:Children in endemic areas of fluorosis are at risk for impaired development of intelligence.

Relationship between Urinary Arsenic Level and Urinary Iodine, Radioiodine Uptake, TSH, FT4 Levels: Research is Based on Experimental and Control Groups

In Bangladesh drinking water is heavily contaminated with arsenic. An estimated 50 million people are at risk from drinking of arsenic contaminated water in Bangladesh and West Bengal in India. Millions of people in many districts of Bangladesh are drinking ground water with arsenic concentrations above acceptable levels (0.05 mg/l) and many of them have already been diagnosed with poisoning symptoms. That is why, in this research an attempt has been made to find the relation between arsenic levels and urinary iodine, radioiodine uptake, thyroid stimulating hormone (TSH) and free thyroxin (FT4) levels in Bangladeshi population. Another purpose has also been made to find the impacts of arsenic level on simple diffuse goiters. This is a case-control analytic study. The study was carried out at the Institute of Nuclear Medicine and Ultrasound, in collaboration with the thyroid out patient department of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. From our analytical results it has been found that, only the variable radioiodine uptake at 24 hours play significant role for reducing the arsenic level. Also, it has been found that iodine deficiency is not only the factor of causing simple diffuse goiter, but arsenic level is also one of the most important factors of causing simple diffuse goiter in Bangladeshi population. DOI: http://dx.doi.org/10.3329/dujps.v10i1.10010 DUJPS 2011; 10(1): 13-20

Associations between microRNA (miR-21, 126, 155 and 221), albuminuria and heavy metals in Hong Kong Chinese adolescents

Background and aimPathogenetic mechanisms underlying albuminuria are not completely understood. Heavy metals might lead to atherosclerosis and kidney damage. miR-21, 126, 155 and 221 regulated endothelial function and might contribute to the development of albuminuria. To date, no clinical trial has explored the relationship between miRNAs, microalbuminuria and heavy metals in human. In this study, we aimed to examine the association between microalbuminuria, miRNAs and heavy metals in adolescents. Materials and methodsFrom a cross-sectional, population-recruited study, we identified 60 school children aged 12–19years with microalbuminuria (defined as spot urine albumin–creatinine ratio >3.5mg/mmol). We compared the urine heavy metals (arsenic, mercury, cadmium and lead) and miRNAs levels (miR-21,126, 155 and 221) with another 60 age-and sex-matched normoalbuminuric adolescents as control. ResultsMean age of the study cohort was 15.5±2.1years. 43% were boys. Among the four miRNAs tested, only miR-21 was associated with microalbuminuria (p=0.02). Urinary arsenic and lead levels had a negative association with both miR-21 and miR-221. No significant association was found between heavy metals examined and microalbuminuria. ConclusionThe results of our study suggest an association between microalbuminuria, miR-21 and heavy metals (arsenic and lead). This might imply that miR-21 is involved in the pathogenetic mechanisms linking heavy metals exposure and albuminuria.

Korea National Survey for Environmental Pollutants in the Human Body 2008: Heavy metals in the blood or urine of the Korean population

Recently, there have been several nationwide episodes involving imported toys contaminated with toxic metals and environmental hormones. In addition, cadmium intoxication has occurred due to soil contamination with cadmium from abandoned metal mines. To investigate the distribution, extent and factors influencing the levels of toxic metals in the blood or urine of the Korean general population over twenty years of age, we studied the blood or urine concentrations of heavy metals in a representative sample of 5087 Koreans in 2008. Multiple biological substrates were collected from each participant to determine the most suitable samples for an environmental health survey system. Information regarding exposure conditions of all subjects was collected by questionnaire-based interviews. The geometric means of the blood lead, mercury and manganese levels were 19.1, 3.23 and 10.8 μg/L, respectively. The geometric means of urinary arsenic and cadmium concentrations were 43.5 and 0.65 μg/L, respectively. Blood mercury and urinary arsenic levels in the Korean general population were significantly higher than in European and American populations. The higher levels of blood mercury and urinary arsenic could be explained by the greater seafood consumption among the Korean population. This biomonitoring study of blood or urine heavy metals in the Korean general population provides important reference data stratified by demographic and lifestyle factors that will be useful for the ongoing surveillance of environmental exposure of Koreans to toxic metals.

Elevated risk of hypertension induced by arsenic exposure in Taiwanese rural residents: possible effects of manganese superoxide dismutase (MnSOD) and 8-oxoguanine DNA glycosylase (OGG1) genes

Heavy metals, including arsenic and lead, may lead to cellular oxidative damage that is linked to hypertension. Manganese superoxide dismutase (MnSOD) is a scavenger of reactive oxygen species, and 8-oxoguanine DNA glycosylase (OGG1) is the major glycosylase that repairs DNA lesions. Interestingly, whether there is an elevated risk of hypertension with arsenic or lead exposure in individuals with genetic variations in MnSOD or OGG1 has not yet been investigated. Questionnaires were administered to 240 Taiwanese rural residents. Blood pressure and biochemical indicators were assessed in each subject. Urinary levels of arsenic and lead were measured with atomic absorption spectrometry; and MnSOD and OGG1 genotypes were identified via polymerase chain reaction. There was a dose-response relationship between urinary arsenic levels and risk of hypertension (P = 0.021, test for trend). However, there was no association between urinary lead levels and hypertension risk. Individuals with high urinary arsenic levels and the MnSOD Val-Ala/Ala-Ala genotypes had a greater risk of hypertension than those with low urinary arsenic levels and the MnSOD Val-Val genotype (odds ratio [OR] = 4.2, 95% confidence interval [CI] = 1.7-10.3). Subjects with a high urinary arsenic level and the OGG1 Cys-Cys genotype also had a greater risk of hypertension than those with a low urinary arsenic level and the OGG1 Ser-Ser/Ser-Cys genotypes (OR = 3.4, 95% CI = 1.1-10.7). Thus, both MnSOD and OGG1 genotypes may be prone to an increased risk of hypertension associated with arsenic exposure.

Heavy Metals Exposure and Hearing Loss in US Adolescents

Hearing loss is common and, in young persons, can compromise social development and educational achievement. Exposure to heavy metals has been proposed as an important risk factor for hearing loss. We evaluated the cross-sectional associations between blood lead, blood mercury, and urinary cadmium and arsenic levels and audiometrically determined hearing loss in participants aged 12 to 19 years in the 2005-2008 National Health and Nutrition Examination Survey after accounting for the complex survey design. There were 2535 individuals available for analysis of blood lead and mercury levels, 878 for urinary cadmium levels, and 875 for urinary arsenic levels. Multivariate logistic regression was used to calculate adjusted odds ratios (ORs) and 95% CIs. A blood lead level greater than or equal to 2 μg/dL (to convert to micromoles per liter, multiply by 0.0483) compared with less than 1 μg/dL was associated with increased odds of high-frequency hearing loss (OR, 2.22; 95% CI, 1.39-3.56). Individuals in the highest quartile of urinary cadmium levels had significantly higher odds of low-frequency hearing loss than those in the lowest quartile (OR, 3.08; 95% CI, 1.02-9.25). There was no overall association between quartiles of blood mercury or urinary arsenic levels and hearing loss. Blood lead levels well below the current recommended action level are associated with substantially increased odds of high-frequency hearing loss.

Urinary inorganic arsenic in residents living in close proximity to a nickel and copper smelter in Ontario, Canada.

The current study determines whether internal exposure to inorganic arsenic for residents living in close proximity to an operating smelter is any different from that for residents living in a similar community without anthropogenic sources of inorganic arsenic. Furthermore, the study examines factors that may contribute to internal inorganic arsenic exposure in these populations. A cross-sectional study was used to determine whether recent internal exposure to inorganic arsenic for residents living in close proximity to an operating smelter with known elevated soil arsenic content is any different from exposure for residents living in a similar socio-demographic community without point sources of arsenic. Personal information was collected from participants during in-home interviews, and first morning void urine samples were obtained to assess recent internal exposure to arsenic. The mean concentration of urinary inorganic arsenic of residents living in the exposed community was 7.11 ug/L (Standard deviation (SD) 4.53, N = 368) and in the non-exposed community was 7.19 ug/L (SD 5.63, N = 321). The difference in urinary inorganic concentration was not statistically significant (p = 0.83). Regression analysis showed that age and sex were significant predictors of internal exposure, with males and younger age groups having higher exposure levels. Based on analyses of data collected, the results did not demonstrate a statistically significant difference in recent internal exposure to inorganic arsenic between the community with and the one without industrial or other point sources of environmental arsenic contamination. However, individual characteristics such as age and sex are important contributors to urinary inorganic arsenic levels.

폐금속 광산지역 토양 중 중금속 농도와 주민의 혈액 및 요중 중금속 농도와의 관련성

Objectives: This study was conducted in order to examine the relationship between heavy metal concentrations in the soil and the level of heavy metals in the blood or urine of 216 local residents living near abandoned metal mines. Methods: Residents around abandoned metal mines were interviewed about their dietary habits, including seafood consumption, medical history, cigarette smoking, and drug history. Metal concentrations in the soil were determined by atomic absorption spectrophotometer (AA-7000, Shimadzu, Japan). Lead (Pb) and cadmium (Cd) contents in the blood or urine were analyzed by GF-AAS (AA-6800, Shimadzu). Mercury (Hg) contents in the blood were determined by means of a mercury analyzer (SP-3DS, NIC). Arsenic (As) content in the soil and urine were measured by a HG-AAS (hydride vapor generation-atomic absorption spectrophotometer). Results: The heavy metal concentrations in the soil showed a log normal distribution and the geometric means of the four villages were 8.61 mg/kg for Pb, 0.19 mg/kg for Cd, 1.81 mg/kg for As and 0.035 mg/kg for Hg. The heavy metal levels of the 216 local residents showed a regular distribution for Pb, Cd, Hg in the blood and As in the urine. The arithmetic means were 3.37 <TEX>${\mu}g$</TEX>/dl for Pb, 3.07 <TEX>${\mu}g$</TEX>/l for Cd and 2.32 <TEX>${\mu}g$</TEX>/l for Hg, 10.41 <TEX>${\mu}g$</TEX>/l for As, respectively. Conclusions: As a result of multi-variate analysis for the affecting factors on the bodily heavy metal concentrations, gender and concentration in the soil (each, p<0.01) for blood lead levels; gender and smoking status (each, p<0.01) for blood cadmium levels; gender (p<0.01) for urine arsenic levels; gender, age and concentration in the soil (p<0.01) for blood mercury levels were shown to be the affecting factors.

A medical geology study of an arsenic-contaminated area in Kouhsorkh, NE Iran

High concentrations of arsenic were determined in sediments from the Kouhsorkh area, Khorasan province, NE Iran. The main rock formations in the area consist of Tertiary volcanic rocks as Tuffaceous sandstone, polymictic conglomerate and andesite. Furthermore, some As-Sb-Au mineralization occurred in this area. Concentrations of arsenic in sediments were determined to range between 4.2 and 268.2 ppm, exceeding US EPA (2004) limits. It seems that young volcanic activity is one of the most important factors for arsenic contamination in this area. The first stage of this medical geology study was done at 2 villages in the Kouhsorkh area in which the arsenic concentration in water is high. People in this residential area suffer from skin diseases including hyperpigmentation, hypopigmentation, keratosis on head, hands, and feet. The 24-h urine specimens were tested for arsenic, the level of total arsenic in urine were determined to range between 13.66 and 75.92 μg/l day, exceeding permissible limits from 5 to 40 μg/day. More systematic studies are needed to determine the link between As exposure and its related diseases.

The polymorphisms of P53 codon 72 and MDM2 SNP309 and renal cell carcinoma risk in a low arsenic exposure area

Our recent study demonstrated the increased risk of renal cell carcinoma (RCC) associated with high urinary total arsenic levels among people living in a low arsenic exposure area. Genomic instability is important in arsenic carcinogenesis. This study evaluated the relationship between the polymorphisms of p53, p21, and MDM2, which plays a role in gene stability, and the arsenic-related RCC risk. Here, we found that p53 Pro/Pro genotype and MDM2 SNP309 GG genotype significantly increased RCC risk compared to the p53 Arg/Arg genotype and MDM2 SNP309 TT genotype. RCC patients with the p53Arg/Arg genotype had a signicantly low percentage of inorganic arsenic, a low percentage of monomethylarsonic acid (MMA), and a high percentage of dimethylarsinic acid (DMA), which indicates efcient arsenic methylation capacity. Subjects with the p53 Arg/Pro + Pro/Pro genotype or MDM2 SNP309 TG+GG genotype, in conjunction with high urinary total arsenic (≥14.02μg/L), had a signicantly higher RCC risk than those with the p53 Arg/Arg or MDM2 SNP309 TT genotypes and low urinary total arsenic. Taken together, this is the first study to show that a variant genotype of p53 Arg72Pro or MDM2 SNP309 may modify the arsenic-related RCC risk even in a non-obvious arsenic exposure area.

URINARY LEVELS OF ARSENIC, LEAD AND MERCURY AMONG CHILDREN AND NEUROBEHAVIOURAL TOXICITY: AN EXPLORATORY STUDY

Background: Diet and living near to chemical/metal industries are a potential source of environmental exposure to metals such as lead, mercury and arsenic, which are recognized causes of neurological disorders in children. Our objective was to explore the relationship between urinary levels of arsenic, lead and mercury, and neurobehavioral performance (subclinical effect) in children aged 9-11. Methods: Spot urine samples were obtained from 79 children recruited from cities representative of five different environmental scenarios in Andalusia (Spain): 14 from urban/residential, 34 from urban/industrialized, 7 from mining, 14 from rural, and 10 from rural/industrialized. Neurobehavioral performance was satisfactorily assessed in 37 boys and 36 girls by the Behavioral Assessment and Research System (BARS) using Spanish instructions. Multielemental ICP-MS was used to quantify urinary levels of arsenic, lead and mercury. General linear models were used including age, gender, social class, global physical activity, and shore fish consumption as covariates, plus the exposure variable (log transformed urinary levels of each metal separately) to predict each of 14 neurobehavioral outcome variables. Results: Higher levels of mercury were associated with a worse performance of the Alternate Hand Finger Tapping (AHFT) test (measures “coordination”) (p=0.03), of the Digit Span Forward test (measuring “attention”) (p=0.08) and of the Errors on Simple Reaction test (measures “response speed”) (p=0.02); and with better performance of the Continuous Performance Hit Latency test (measures “attention”) (p=0.001). Children with higher arsenic levels scored better on the Continuous Performance False Alarm Latency test (p=0.08), and tended to score worse on the AHFT test (p=0.10). No statistically significant associations were observed for urinary lead, although children with higher levels tended to perform better with the AHFT test (p=0.09), and worse with the Continuous Performance Correct Rejections test (p=0.15). Conclusions: Our results suggest that urinary levels of mercury are related with poorer neurobehavioral performance among children.

THE ROLE OF GENDER IN INORGANIC ARSENIC INDUCED OXIDATIVE STRESS AMONG BANGLADESHI POPULATION EXPOSED TO HIGH ARSENIC THROUGH DRINKING WATER

Background: Arsenic acts as a carcinogen may be due to oxidative stress induction through the generation of reactive oxygen species (ROS). Gender disparity has been reported in many arsenic-exposure related diseases like cardiovascular diseases, hypertension, liver diseases, as well as skin lesions or cancers. However, no study had been reported about gender disparity in arsenic induced oxidative stress in Bangladeshi arsenic-exposed population. Objective: The objectives of the study are to examine the levels of urinary 8-OHdG and F2α –isoprostane, two established oxidative stress biomarkers, in relation to the urinary arsenic within Bangladeshi arsenic-exposed men and women. Methods: Data were obtained from 219 healthy participants, aged 18-45 years, from two communities of southern-west part of Bangladesh in August 2009. One hundred four participants were participated from high arsenic-contaminated area and other 115 participants from arsenic free area. Results: Urinary arsenic was positively associated with oxidative biomarkers-namely 8-OHdG and F2α-isoprostane (r=0.59, p&lt;0.001 and r=0.43, p&lt;0.001, respectively). The exposed group showed higher urinary arsenic (Geometric mean 166 µg/g Cr 95% CI 102.8-230.9) than the non-exposed group (Geometric mean 54 µg/g Cr, 95% CI 38.8-70.9). Higher 8-OHdG level was found in As-exposed group (Geometric mean 8.4 ng/mg Cr, 95% CI 2.5-14.2 vs Geometric mean 6.5 ng/mg Cr, 95% CI 3.9-9.6) than in non-exposed group, but result was different for F2α-isoprostane (Geometric mean 5.5 ng/mg Cr, 95% CI 4.1-6.9 vs Geometric mean 7.0 ng/mg Cr, 95% CI 2.8-11.2). Among arsenic-exposed subjects urinary arsenic and 8-OHdG levels were significantly lower (p&lt;0.05) in women than men. In case of F2α-isoprostane, women have higher values than men within the non-exposed group, but no sex difference was found in As-exposed group. Conclusions: The results suggest that oxidative DNA damage and lipid peroxidation were associated with arsenic exposure, which were sex-dependent to some extent.

COMMUNITY PARTICIPATION TO LOWER ARSENIC EXPOSURE MORE EFFECTIVELY IN BANGLADESH

Background/Aims: Millions of villagers in Bangladesh drink groundwater containing elevated levels of arsenic from their own well water even though arsenic safe water is often available within short walking distance. Well water arsenic testing has been shown to reduce arsenic exposure; however there have been no studies looking at the effectiveness of having a local villager conduct the well testing program. Methods: We conducted a cluster-based randomized controlled trial(RCT) of 1000 households in 20 villages to investigate the impact of having a local person present within a village in comparison to an outside person conducting water arsenic testing and arsenic education in Singair,Bangladesh. Six months after the intervention the rate of well switching and the change in urinary arsenic from baseline was determined. This is the first RCT of arsenic education conducted in Bangladesh using a biological outcome indicator. Results: The trained arsenic testers were able to convince 58% of study households with unsafe wells to switch to alternative drinking water sources. Although we did not find a statistically significant difference between the local and outside tester villages, this overall rate is more than twice the rate of well switching observed in areas that only received well testing from the nationwide Bangladesh Arsenic Mitigation Water Supply Project(BAMWSP). Furthermore the urinary arsenic levels of all study participants with unsafe wells that switched to safe drinking water sources(&lt;50µg As/L) dropped from an average of 215µg As/g creatinine at baseline to 133µg As/g creatinine at follow-up, a 38% reduction in average urinary arsenic content. Those with unsafe wells that did not switch had an average urinary arsenic of 235µg As/g creatinine at follow-up. Conclusions: The success of this intervention demonstrates that training upazila level staff to provide arsenic testing and education is an effective means of reducing arsenic exposure in villages in Bangladesh.

Study of the DNMT3B variant genotype among Iranian sporadic breast cancer in compare with normal individuals

Our previous study showed that high urinary total arsenic levels were associated with higher odds ratio (OR) for renal cell carcinoma (RCC). Single nucleotide polymorphisms (SNPs) of DNA methyltransferases (DNMTs) might influence DNMT enzyme activity associated with tumorigenesis. In this study, we investigated the association of five SNPs from DNMT1 (rs8101626 and rs2228611), DNMT3A (rs34048824 and rs1550117), and DNMT3B (rs1569686) with the risk of clear cell renal cell carcinoma (ccRCC). We also examined the combined effects of DNMT genotypes and urinary arsenic levels on ccRCC risk. We conducted a hospital-based case-control study, which included 293 subjects with ccRCC and 293 age- and gender-matched controls. The urinary arsenic species were determined by a high performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Genotypes were investigated using polymerase chain reaction and restriction fragment length polymorphism analyses. We observed that the DNMT1 rs8101626 G/G genotype was significantly associated with reduced odds ratio (OR) of ccRCC [OR = 0.38, 95% confidence interval (CI) 0.14–0.99]. Subjects with concurrent DNMT1 rs8101626 A/A + A/G and DNMT3A rs34048824 T/T + T/C genotypes had significantly higher OR for ccRCC [OR = 2.88, 95% CI 1.44–5.77]. Participants with the high-risk genotype of DNMT1 rs8101626 and DNMT3A rs34048824 with concurrently high urinary total arsenic levels had even higher OR of ccRCC in a dose-response manner. This is the first study to evaluate variant DNMT1 rs8101626 and DNMT3A rs34048824 genotypes that modify the arsenic-related ccRCC risk in a geographic area without significant arsenic exposure in Taiwan.

Exposure assessment to heavy metals in general population in an area at high environmental risk through biological monitoring

ObjectivesIn areas at high environmental risk, a major issue is the correct assessment of the exposure of general population to industrial pollutants. The objectives were: to evaluate the exposure to...

Altered gene expression by low-dose arsenic exposure in humans and cultured cardiomyocytes: assessment by real-time PCR arrays.

Chronic arsenic exposure results in higher risk of skin, lung, and bladder cancer, as well as cardiovascular disease and diabetes. The purpose of this study was to investigate the effects on expression of selected genes in the blood lymphocytes from 159 people exposed chronically to arsenic in their drinking water using a novel RT-PCR TaqMan low-density array (TLDA). We found that expression of tumor necrosis factor-α (TNF-α), which activates both inflammation and NF-κB-dependent survival pathways, was strongly associated with water and urinary arsenic levels. Expression of KCNA5, which encodes a potassium ion channel protein, was positively associated with water and toe nail arsenic levels. Expression of 2 and 11 genes were positively associated with nail and urinary arsenic, respectively. Because arsenic exposure has been reported to be associated with long QT intervals and vascular disease in humans, we also used this TLDA for analysis of gene expression in human cardiomyocytes exposed to arsenic in vitro. Expression of the ion-channel genes CACNA1, KCNH2, KCNQ1 and KCNE1 were down-regulated by 1-μM arsenic. Alteration of some common pathways, including those involved in oxidative stress, inflammatory signaling, and ion-channel function, may underlay the seemingly disparate array of arsenic-associated diseases, such as cancer, cardiovascular disease, and diabetes.

Effects of low-level arsenic exposure on urinary N-acetyl-β-D-glucosaminidase activity

This study was aimed to evaluate whether renal tubular function is impaired by exposure to relatively low concentrations of arsenic. Mean urinary arsenic concentrations and N-acetyl-β-D-glucosaminidase (NAG) activities were compared among 365 and 502 Korean men and women, respectively, in relation to gender, smoking, alcohol consumption, and recent seafood consumption. The study subjects were divided into 4 groups according to urinary NAG activity and seafood consumption prior to urine sampling, and the correlation between arsenic concentration and urinary NAG activity was tested for each group. The mean urinary arsenic level was higher in women, non-smokers, and non-drinkers in comparison to men, smokers, and drinkers, respectively. Individuals who consumed seafood within 3 days prior to urine sampling showed a higher mean urinary arsenic level than those who did not. The correlation between urinary arsenic concentration and NAG activity in urine was significant only in subjects who did not consume seafood within 3 days prior to urine sampling and whose urinary NAG activity was 7.44 U/g creatinine (75th percentile) or higher. The urinary arsenic concentration was a significant determinant of urinary NAG activity in subjects with NAG activity higher than 7.44 U/g creatinine and especially in those who had not consumed seafood recently. These facts suggest that a relatively low-level exposure to inorganic arsenic produces renal tubular damage in humans.