Urinary Arsenic Levels Research Articles

Environmental doses of arsenic exposure are associated with increased reproductive-age male urinary hormone excretion and in vitro Leydig cell steroidogenesis

Humans are ubiquitously exposed to arsenic from multiple sources, and chronic arsenic exposure may be associated with male reproductive health. Although association regarding arsenic exposure and sex hormone secretion in blood has been reported, sex hormone excretion in urine studies is lacking. Urinary sex hormone excretion has emerged as a complementary strategy to evaluate gonadal function. Herein, we determined the associations between environmental exposure to arsenic and urinary sex hormone elimination and in vitro Leydig cell steroidogenesis. Concentrations of arsenic and testosterone (T), estradiol (E2) and progesterone (P) in repeated urine samples were determined among 451 reproductive-age males. Moreover, an in vitro Leydig cell MLTC-1 steroidogenesis experiment was designed to simulate real-world scenarios of low human exposure. Multivariable linear regression models were used to assess the associations of urinary arsenic levels with urinary hormones. Urinary arsenic concentrations were positively associated with urinary sex hormone (T, E2, and P) levels. An in vitro test further demonstrated that a population-based environmental exposure range (0.01–5 μM) of arsenic induced Leydig cell steroidogenesis potency. Our results indicate that low-dose arsenic exposure exhibits an endocrine disrupting effect by stimulating Leydig cell steroidogenesis and accelerating urinary steroid excretion, which extends previous knowledge of the inverse association of high-dose arsenic exposure with sexual steroid production that is assumed to be anti-androgen.

Association between the polymorphism of three genes involved in the methylation and efflux of arsenic (As3MT, MRP1, and P‐gp) with lung cancer in a Mexican cohort

AbstractLung cancer is the most common neoplasm and the primary cause‐related mortality in developed and in most of nondeveloped countries. Epidemiological studies have demonstrated that even at low arsenic doses, the lungs are one of the main target organs and that chronic arsenic exposure has been associated with an increase in lung cancer development. Among the risk factors for cancer, arsenic methylation efficiency (As3MT) and the clearance of arsenic from cells by two members of the ATP‐binding cassette (ABC) transporter family (multidrug resistance protein 1 [MRP1] and P‐glycoprotein [P‐gp]) play an important role in processing of arsenic and decreasing its intracellular levels. This study aimed to evaluate the association between chronic exposure to arsenic with polymorphism of three proteins involved in arsenic metabolism and efflux of the metalloid in subjects with lung cancer. Polymorphism in As3MT, MRP1, and P‐gp modified the arsenic metabolism increasing significantly the AsV urinary levels. A significant association between MRP1 polymorphisms with an increase in the risk for cancer was found. The high inorganic arsenic urinary levels registered in the studied subjects suggest a reduction in the efficiency of As3MT, MRP1, and P‐gp firstly because of gene polymorphisms and secondarily because of high internal inorganic arsenic levels. MRP1 polymorphism was associated with a twofold increase in the risk of lung cancer.

Arsenic exposure and Measles Antibody Titers in the US Children: NHANES 2003-2004 and 2009-2010.

Background/Aim: Exposure to arsenic during childhood is associated with adverse health problems including cancers and non-cancerous diseases. However, little is known about its effect on vaccine-related humoral immunity in children. In this study, we examined the association between arsenic exposure and measles antibody titers in US children. Methods: The association between urinary arsenic and serum measles antibody levels in the US children aged between 6 and 11 was investigated, based on the National Health and Nutrition Examination Survey (NHANES) 2003-2004 and 2009-2010. The total urinary arsenic level was calculated by summing inorganic arsenic and their metabolites (arsenite, arsenate, methylarsonic acid, and dimethylarsinic acid), and was divided by the level of urinary creatinine. The generalized linear regression was conducted to evaluate the association, adjusted for the cycle, age, race, undergrowth, secondhand smoking, and poverty index ratio. Stratified analyses were conducted by gender and serum folate levels using the median as cutoff (18.7 ng/mL). Results: The level of serum measles antibody titers decreased by 28.1% (95%CI: −44.2%, −12.0%) per tertile increase in the concentration of creatinine-adjusted urinary arsenic among boys with serum folate levels lower than 18.7 ng/ml. However, no associations were observed in boys with high serum folate levels and girls. Conclusion: Our stratified analysis showed the inverse association between arsenic exposure and measles antibody level among boys with lower folate intake. This study will provide the basis for an intervention strategy to protect children’s health from arsenic exposure.

Biomonitoring of metals in inhabitants of Northern Chile: implications of surveillance in areas with historical exposures

Background: The presence of toxic metals in human populations is strongly associated with chronic diseases and should be monitored especially in communities with a history of chronic exposures as occurs in northern Chile.Objective: to establish concentrations and prevalence of exposure to metals in residents of the city of Antofagasta, Chile, and its main risk factors.Methods: a cross-sectional study in Antofagasta was made. The sample (1203 adults) had populational representability at the city level. Sociodemographic information, health status, and sources of exposure to metals were collected in the participants. Urinary Inorganic Arsenic (InAs), Cadmium (Cd), Chromium (Cr) and Mercury (Hg) levels, and Lead (Pb) in blood were measured using NIOSH methodology by Inductively coupled plasma atomic emission spectroscopy (ICP-AES).Results:The sample had an average age of 42.7 years, with an average residence time in the city of 30 years, predominantly women (54.5%), high smoking (51.5%), high occupation rate in mining activities (22.6%).Using cutoff used by the health authorities (35µg /L for urinary InAs, the prevalence was 8% in adults and 12.3% in children. However, 75% of the population has levels below 21.9 µg / L. The main factors associated with high levels of urinary inorganic arsenic in adults were sex (β= 3.12, IC 95% 0.2-6.05 for males) and low schooling (β= 7.1, IC 95% 0.4-14.6 in people having less 8 y of education). People residing more than 500 meters from fixed sources had higher InAs levels. Other metals are below risk levels defined by health authorities.Conclusions It is urgent that in this city all the sources related to InAs must be verified and develop social interventions and environmental health surveillance in order to reduce involuntarily exposure to this metalloid.

Effect of gene-environment interaction (arsenic exposure - PON1 Q192R polymorphism) on cardiovascular disease biomarkers in Mexican population

Cardiovascular diseases (CVDs) are the primary cause of death worldwide. However, little is known about how the interaction between risk factors affects CVDs. Therefore, the aim of this study was to evaluate the effect of the gene-environment interaction (arsenic exposure x PON1 Q192R polymorphism) on serum levels of CVDs biomarkers in Mexican women. Urinary arsenic levels (UAs) ranged from 5.50–145 μg/g creatinine. The allele frequency was 0.38 and 0.62 for the Q and R alleles, respectively. Moreover, significant associations (p<0.05) were detected between UAs and CVDs biomarkers (ADMA, FABP4, and miR-155). Comparable data were found when CVDs biomarkers were evaluated through PON1 genotype, significant (p<0.05) higher serum concentrations of CVDs biomarkers were identified in R allele carriers compared to levels found in Q allele carriers. Besides, a gene-environment interaction was documented. The results of this study we believe should be of significant interest to regulatory authorities worldwide.

Cadmium and Lead Levels in Blood and Arsenic Levels in Urine among Schoolchildren Living in Contaminated Glassworks Areas, Sweden.

The Kingdom of Crystal, an area in southern Sweden famous for its many glassworks, is historically heavily burdened by pollution from this industry. Glass crust containing cadmium (Cd), lead (Pb), and arsenic (As) has been deposited around the area and used as filling. The purpose of this study was to monitor whether the high levels of metals in the contaminated soil were reflected in blood and urine among school children in this area. Blood and urine samples were collected from 87 children in 2017. The levels of cadmium (Cd-B) and lead (Pb-B) found in blood were determined by inductively coupled plasma mass spectrometry (ICP-MS). The speciation of As in urine (As-U) was performed by ion chromatography. The geometric mean of Cd-B and Pb-B among the children were 0.09 μg/L and 9.9 μg/L respectively. The geometric mean of inorganic As (AsIII and AsV) with metabolites in urine was 6.1 μg/L and 6.94 μg/g creatinine. Children in the study area had blood levels of Pb and Cd that correspond to levels generally found in Swedish children. The levels of inorganic As and its metabolites in urine were low and in the same magnitude as other children in Europe and the U.S.

S1065 Arsenic Exposure and Risk of Liver Injury Among U.S. Adults: An Association Modified by Gender

INTRODUCTION: Arsenic has toxic effects on multiple organ systems; however, arsenic toxicity on the liver has not been well explored. Therefore, we examined the association between arsenic exposure and serum ALT, a marker for liver injury and effect modification by gender. METHODS: Individuals >19 years of age from 7 cycles of the National Nutrition and Health Examination Survey (NHANES 2003–16) were included. Associations between serum ALT and creatinine-standardized urinary concentrations of total and 7 arsenic forms were examined. Data were summarized with mean (standard deviation) or frequencies. Urinary arsenic and serum ALT were log-transformed due to right-skewed distributions. We used survey-weighted linear regression without and with adjustments for gender, age, diabetes, hypertension, race, smoking, alcohol use, estimated GFR, and body mass index(BMI). Effect-modification by gender was examined by with an interaction term between gender and arsenic forms. RESULTS: Of the 12,439 participants, 52% were females, 33% hypertensives, 9% were diabetics, 54% were non-smokers, and 68% were whites. The mean age was 48 years. BMI 29 Kg/m2, ALT 26 U/L, and total urinary arsenic 18.4 ug/L. As compared to females, males had significantly higher ALT (30.3 vs 21.9; P < 0.001) and total urinary arsenic levels (19.7 vs 17.3 P = 0.02). In adjusted models, each 10% increase in urinary total arsenic, dimethylarsonic acid, trimethylarsine oxide was associated with 0.1%, 0.4%, and 0.2% increase in serum ALT respectively (all P-values< 0.01); ALT increase with other urinary arsenic forms was not significant. Females had larger increases in ALT than males for 5 arsenic forms; for each 10% increase in arsenous acid, arsenic acid, arsenocholine, monomethylarsonic acid, and dimethylarsenic acid were associated with 0.3%, 0.6%, 0.4%, 0.6%, and 0.4% larger increase in ALT than males (all P < 0.05) (Figure). CONCLUSION: Urinary arsenic levels within an acceptable range (total urinary arsenic< 100ug/L) are associated with a small but significant risk of liver injury as measured by elevation in serum ALT. Females are particularly at a higher risk of liver injury than males. The clinical significance of this liver injury needs examination in longitudinal studies.Figure 1

Breast Cancer Disease and Arsenic: “Geological Behavior (GBR) as Key “

Geology may appear remote from human health. However, rocks are the fundamental building blocks of the Earth’s surface, full of important minerals and chemical elements. Rock weathering and alteration products not only form our soils to support our crops but provide essential elements to build biology. Some heavy metals are carcinogenic, and some only affect the body’s ability to produce red and white cells. In fact, any heavy metal affects any part of the body due to our geological behavior (GBR). For example, a heavy metal may not cause any side effects by contact with the skin, even when swallowed, and may not cause serious harm, but inhaling the vapor of that heavy, toxic metal can cause severe damage to the lungs. Some heavy and quasi metals are more toxic, and some forms of heavy metal compounds are even more dangerous than other forms. Toxic and hazardous heavy metals like arsenic, lead, mercury, zinc, chromium and iron are found in a variety of personal care products, e.g., lipstick, whitening toothpaste, eyeliner and nail color. We use the Anodic Stripping voltammetry (ASV) method for arsenic detection, utilizing the PDV6000 + analyzer (Manufactured B3 Electronics, Perth Australia) configured with a solid gold electrode for total as analyses. Sample Preparation: Spot urine samples were collected from most of the participants from 1 January 2018 to 30 March 2020 after face to face interviews. Women with missing information on adjustment variable(s) were included in the analysis in a separate category for adjustment. Results: Our studies were focus in describing the mean Urinary Arsenic levels (u As) residents of in the central zones of Shiraz, Fasa, Abadeh, Jahrom and Marvdasht to compare the effect of diet such as consuming canned or frozen foods, Consume rice daily, smoking habits and lifestyle on the incidence of Breast. Conclusion: Cancer with arsenic compounds has been reported in many parts of the world. The disease affects all organs of the body, and every year many victims of cancer suffer from severe symptoms and even death. Arsenic compounds are present in the human body and environment in an inorganic and organic form. Inorganic arsenic includes arsenite and arsenic, can also be presented in the environment in the form of methyl (monthly arsenic acid and dimethyl arsenic acid). Arsenic, especially inorganic arsenic, is well absorbed through the gastrointestinal tract rivers (80% -90%) and will be scattered throughout the body. It is often metabolized by methylation and excreted mainly in the urine. Methylation of inorganic arsenic compounds is said to undergo a detoxification process.

Effect of plasma selenium, red blood cell cadmium, total urinary arsenic levels, and eGFR on renal cell carcinoma

High total urinary arsenic concentrations and low estimated glomerular filtration rate (eGFR) increase the risk of renal cell carcinoma (RCC). This study aimed to determine whether other metals or metalloids can affect RCC. A total of 401 patients with RCC and 774 age- and sex-matched controls were recruited between November 2006 and December 2012 in Taiwan. Surgical resection or image-guided biopsy of renal tumors was performed to pathologically verify RCC. High-performance liquid chromatography linked to a hydride generator and atomic absorption spectrometer were used to measure the urinary arsenic species concentrations. Inductively coupled plasma mass spectrometry was used to determine plasma selenium and red blood cell cadmium and lead concentration. Plasma selenium levels were inversely related to RCC, whereas red blood cell cadmium levels were directly related to RCC. The odds ratio (OR) and 95% confidence interval (CI) were 0.14 (95% CI, 0.10–0.20) and 1.33 (95% CI, 1.03–1.72), respectively. A low plasma selenium level tended to interact with high total urinary arsenic levels or with high red blood cell cadmium concentration to increase the OR of RCC. In particular, low eGFR multiplicatively interacted with high red blood cell cadmium concentration to increase the OR of RCC (Pinteraction=0.003). This study was the first to find a significant multiplicative interaction between eGFR and the red blood cell cadmium levels on the increased OR of RCC.

Arsenic in the Pathway to Cardiovascular Diseases: Arsenic May Mediate Lipid Profile in Adults

Abstract Objectives Recent studies indicate arsenic exposure may increase the risk of cardiovascular diseases, but the mechanism of this association is still unknown. This study explores the relationship between urine arsenic levels and serum cholesterol and triglycerides. Our hypothesis is that greater arsenic levels may be associated with dyslipidemia. Methods We used data from a subpopulation (n = 1203, 25 – 65 years of age) of an ongoing cohort study, the China Health and Nutrition Survey, which has collected data from participants on demographics, arsenic levels, lipid profile, and many other variables. We measured arsenic levels from urine samples with inductively coupled plasma mass spectrometry and serum lipid profile with an automated analyzer. With data collected in 2015, we used logistic regressions to analyze cross-sectional associations between arsenic exposure (categorized into three tertiles) and dyslipidemia, controlling for potential confounding variables like age, gender, residence area, occupation, and education level. Results Among this population, the median urine arsenic level was 19.3 µg/L (range 0 – 492.2 µg/L). The prevalence of high total cholesterol (defined as cholesterol ≥200 mg/dL) and high triglycerides (defined as total triglycerides ≥150 mg/dL) was 43.5% and 30.2%, respectively. After adjusting for potential cofounders, the odds ratio and 95% confidence interval was 1.41 (1.05, 1.88) for having high cholesterol, 1.41 (1.01, 1.97) for having high triglycerides and 1.42 (1.03, 1.97) for having low HDL level (defined as ≤40 mg/dL for men or 50 mg/dL for women), among participants in the higher arsenic exposure tertile compared to those in the lower tertile. Conclusions Our findings suggest that arsenic exposure, even in moderate concentrations, is positively associated with dyslipidemia. These results indicate that arsenic-mediated dyslipidemia may be a pathway to cardiovascular diseases. Funding Sources The Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD30880, P2C HD050924); the National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK104371); the National Institutes of Health (NIH); the NIH Fogarty International Center (D43 TW009077); the National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention.

Children exposure to inorganic and organic arsenic metabolites: A cohort study in Northeast Italy

The aim of this study was to provide urinary levels of total arsenic (TAs) and As species as arsenobetaine (AsB), arsenocholine (AsC), inorganic As (i.e., [As(III)+As(V)]), methylarsonic acid (MMA) and dimethylarsinic acid (DMA) in 7 year-old-children (n = 200) enrolled in the Northern Adriatic Cohort II (NACII), a prospective cohort in a coastal area of Northeast Italy. TAs was determined by sector field-inductively coupled plasma mass spectrometry (SF-ICP-MS) and AsB, AsC, As(III), As(V), MMA and DMA by ion chromatography coupled to ICP-MS (IC-ICP-MS). The geometric mean (GM) for TAs was 12.9 μg/L and for [iAs + MMA + DMA] was 4.26 μg/L. The species AsB (GM of 5.09 μg/L) and DMA (GM of 3.20 μg/L) had the greatest percentage contribution to TAs levels; a greater percentage contribution from AsB is seen at TAs >10 μg/L and from DMA at TAs <10 μg/L. Urinary [iAs + MMA] levels were positively associated with [iAs + MMA + DMA] and DMA with AsB levels. Fish, shellfish and crustaceans consumption increased the AsB and TAs levels, while rice intake, mothers’ education level and selenium (Se) concentration influenced the DMA concentration. Children have a high capacity to metabolize and detoxify the iAs because of the higher secondary methylation index (ratio DMA/MMA) with respect to primary methylation index (ratio MMA/iAs). In addition, the median level of [iAs + MMA + DMA] in the whole population of children was lower than the Biomonitoring Equivalent (BE) value for non-cancer endpoints. Also the Margin of Safety (MOS) value based on the population median was greater than 1, thus the exposure to the toxicologically relevant As species was not likely to be of concern.

BIOMONITORING OF A POPULATION RESIDING NEAR TO MINE TAILINGS IN GUANAJUATO, MEXICO

Some metals present in residues coming from mining activities can damage DNA. A preliminary evaluation was carried out to determine the genotoxic effects on a resident population from a mining area in Xichú, Guanajuato, Mexico. Blood lead levels (BLL), and arsenic levels in urine (AsU), were measured as biomarkers of exposure. Hematological damage was evaluated trough hematocrit, hemoglobin and activity of enzyme delta-aminolevulinic dehydratase (δ-ALAD). DNA damage in blood cells was evaluated by comet assay. BLL (7.5 ± 1.2 and 7.9 ± 3.3 μg/dL) and AsU (25.2 ± 15.8 and 18.3 ± 18.4 μg/g creatinine) were found in children and adults, respectively. Of the children and adults, 100 and 91.7 %, respectively had levels of enzyme activity below 20 U/L erythrocytes. Regarding DNA damage, the children showed an Olive tail moment of 5.0 ± 1.6 and a tail length of 40.9 ± 4.9 μm, of similar magnitude than adults (4.6 ± 1.0 and 41.8 ± 5.9 μm, respectively). In conclusion, this preliminary study describes the health risk scenario of population near the mine, nevertheless, more studies are needed in the area.

A case-control study of arsenic exposure with the risk of primary ovarian insufficiency in women.

Arsenic, a well-known toxic metalloid, is ubiquitously existed in environment. Arsenic exposure has been associated with female reproductive health. However, a potential association between arsenic exposure and primary ovarian insufficiency (POI) in women has not been recognized yet. In this case-control study, a total of 169 POI cases and 209 healthy controls were recruited to determine urinary concentrations of arsenic and serum levels of reproductive hormones (follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Mullerian hormone (AMH) and estradiol). The median concentration of urinary arsenic in cases (21.5μg/L, 28.0μg/g for creatinine adjustment) was significantly higher than that of controls (13.8μg/L, 19.3μg/g for creatinine adjustment). Urinary arsenic concentrations were significantly positively associated with the risk of POI (adjusted odds ratio (OR) = 2.66, 95% CI: 1.43-4.95 for the highest vs lowest tertile of arsenic, p = 0.002; p for trend = 0.004). We also assessed the associations between arsenic exposure and reproductive hormones that are important for ovarian functions. FSH and LH levels were positively associated with urinary arsenic, whereas AMH and estradiol levels were negatively correlated with this element. This study provided evidence that arsenic exposure could be the potential risk factor for POI in women.

Polymorphism of nucleotide binding domain-like receptor protein 3 (NLRP3) increases susceptibility of total urinary arsenic to renal cell carcinoma

Our study showed that total urinary arsenic concentrations were positively correlated with renal cell carcinoma (RCC). Chronic inflammation is a key player in the development of RCC. This study explored the association between nucleotide-binding domain-like receptor protein 3 (NLRP3) genotypes and the development of RCC. We also investigated whether any of the NLRP3 genotypes modified the risk between arsenic and RCC. We recruited 350 RCC patients and 700 age-sex matched controls. RCC was confirmed by pathological assessment following surgical resection or image-guided biopsy of a renal tumor. Fifteen sites of NLRP3 gene polymorphisms were identified using the Agena Bioscience MassARRAY platform. The concentrations of the urinary arsenic species were determined by HPLC-HG-AAS. There was a significant dose-dependent association between arsenic and RCC. In addition, six of thirteen NLRP3 alleles, including rs12239046 C, rs10925025 G, rs1539019 C, rs10925026 A, rs10157379 T, and rs12143966 A, had increased odds ratios (ORs) for RCC than other NLRP3 alleles. Among these sites, we found the novel haplotype of five tag-SNPs (C-A-A-A-A) was significantly related to RCC, the OR and 95% confidence interval was 1.44 (1.08–1.92). Furthermore, participants with high total urinary arsenic levels and the NLRP3 rs1539019 C allele had significantly multiplicative and additive interactions for the risk of RCC (p interaction = 0.012). This study is the first to identify the modified effects of NLRP3 risk alleles involved in the association between arsenic and RCC risk in a population with low arsenic exposure.

Urinary Arsenic Species are Detectable in Urban Underserved Hispanic/Latino Populations: A Pilot Study from the Study of Latinos: Nutrition & Physical Activity Assessment Study (SOLNAS).

Background: Hispanics/Latinos represent >15% of the United States (US) population and experience a high burden of cardiovascular disease (CVD) and diabetes. Dietary exposure, particularly to arsenic (As), may be associated with CVD and diabetes in Hispanics/Latinos. Rural populations in the US exposed to As in drinking water have increased risk of diabetes and CVD; however, little is known about the risk among urban populations with low As in water who are mostly exposed to As through food. Methods: To explore the levels of inorganic arsenic exposure (the sum of inorganic and methylated arsenic species in urine, ∑As, corrected by a residual-based method) in persons of Hispanic/Latino origin, we conducted a pilot study quantifying urinary arsenic levels among 45 participants in the Study of Latinos: Nutrition & Physical Activity Assessment Study (SOLNAS). Results: The median (interquartile range) of the urinary arsenic species (µg/L) were as follows: inorganic As 0.6 (0.4, 1.0), monomethylarsonic acid 1.2 (0.7, 1.9), dimethylarsinic acid 7.2 (4.3, 15.3), and ∑As 6.0 (4.3, 10.5). Conclusions: This study adds to the existing evidence that harmful forms of arsenic are present in this group of Hispanics/Latinos.

HOGG1 promoter methylation, hOGG1 genetic variants and their interactions for risk of coal-borne arsenicosis: A case-control study

To identify the effect of hOGG1 methylation, Ser326Cys polymorphism and their interactions on the risk of coal-borne arsenicosis, 113 coal-borne arsenicosis subjects and 55 reference subjects were recruited. Urinary arsenic contents were analyzed with ICP-MS. hOGG1 methylation and Ser326Cys polymorphism was measured by mehtylation-specific PCR and restriction fragment length polymorphism PCR in PBLCs, respectively. The results showed that the prevalence of methylated hOGG1 and variation genotype (326 Ser/Cys & 326 Cys/Cys) were increased with raised levels of urinary arsenic in arsenicosis subjects. Increased prevalence of methylated hOGG1 and variation genotype were associated with raised risk of arsenicosis. Moreover, the results revealed that variant genotype might increase the susceptibility to hOGG1 methylation. The interactions of methylated hOGG1 and variation genotype were also found to contribute to increased risk of arsenicosis. Taken together, hOGG1 hypermethylation, hOGG1 variants and their interactions might be potential biomarkers for evaluating risk of coal-borne arsenicosis.

PBMC gene expression profiles of female Bangladeshi adults chronically exposed to arsenic-contaminated drinking water

Arsenic, a class I human carcinogen, is ubiquitously found throughout the environment and around the globe, posing a great public health concern. Notably, Bangladesh and regions of West Bengal have been found to have high levels (0.5–4600 μg/L) of arsenic drinking water contamination, and approximately 50 million of the world’s 200 million people chronically exposed to arsenic in Bangladesh alone. This study was carried out to examine genome-wide gene expression changes in individuals chronically exposed to arsenic-contaminated drinking water. Our study population includes twenty-nine Bangladeshi female participants with urinary arsenic levels ranging from 22.32 to 1828.12 μg/g creatinine. RNA extracted from peripheral blood mononuclear cells (PBMCs) were evaluated using RNA-Sequencing analysis. Our results indicate that a total of 1,054 genes were significantly associated with increasing urinary arsenic levels (FDR p < 0.05), which include 418 down-regulated and 636 up-regulated genes. Further Ingenuity Pathway Analysis revealed potential target genes (DAPK1, EGR2, APP), microRNAs (miR-155, -338, −210) and pathways (NOTCH signaling pathway) related to arsenic carcinogenesis. The selection of female-only participants provides a homogenous study population since arsenic has significant sex dependent effects, and the wide exposure range provides new insight for key gene expression changes that correlate with increasing urinary arsenic levels.

Exposure to arsenic and lead in children from Salamanca México, effects on telomeric lengthening and mitochondrial DNA.

Levels of urinary arsenic and levels of lead in blood were measured in children attending elementary schools located in an industrial zone in Salamanca, México. Its possible effects using telomere length and mitochondrial DNA copy number as biomarkers of genomic disequilibrium by oxidative stress were studied. Eighty-eight children (6-15years old) were included and urine samples were collected for quantification of arsenic, while lead was measured in blood samples using inductively coupled plasma mass spectrometry (ICP-MS). DNA was isolated from peripheral blood and relative telomere length and the mitochondrial DNA copy number were determined by real-time PCR. The geometric mean of urinary arsenic was 54.16μg/L (11.7-141.1μg/L). Ninety-eight percent of the children were above 15μg/L (biomonitoring equivalent value). With respect to the concentration of lead in blood, the mean was 3.78μg/dL (LOD-22.61), where 24.5% of the participants had equal or above the reference value (5μg/dL; Mexican Official Norm NOM-199-SSA1-2000, 2017). A positive association between urinary arsenic and telomere length was found (β = 0.161; 95% CI: 0.12; 0.301; P = 0.034), while lead blood concentrations were negatively associated with mitochondrial DNA copy number (β = - 0.198; 95% CI: - 2.81; - 0.17; P = 0.019), after adjusting by age, sex, and total white blood cell count. Differences in the mitochondrial DNA content were observed in children with lead blood levels from 2.5μg/dL, (P ≤ 0.001), suggesting an effect at lead exposure levels considered acceptable (< 5μg/dL). In conclusion, children living in an industrial area in Salamanca showed an exposure to arsenic and lead and an impact on telomere length and mitochondrial DNA content associated with arsenic and lead exposure, respectively.

Heavy metal exposure, oxidative stress and semen quality: Exploring associations and mediation effects in reproductive-aged men.

Heavy metal exposure induces oxidative stress, which is critical for adverse male reproductive health. To explore the mediating effect of oxidative stress on the relationship of heavy metal exposure with semen quality. Urinary levels of three oxidative stress markers, semen quality, and urinary arsenic, cadmium and lead were examined among 1020 men. Multivariate linear regression was applied to explore cross-sectional associations, and the role of oxidative stress as mediators was investigated. Quartiles of metals showed significant dose-dependent relationships with increasing levels of 8-hydroxy-2deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA). Significant or suggestive associations were also found between urinary 8-OHdG levels and the percentage of normal sperm morphology (ptrend<0.001), between urinary 8-isoPGF2α levels and total motility (ptrend=0.052), progressive motility (ptrend=0.050) respectively. The mediation analysis showed that about 14.59%, 18.06%, 15.35% or 16.49% of the association between arsenic/cadmium exposure and the decreased total motility/progressive motility was mediated by 8-isoPGF2α, respectively. In addition, about 16.47% of the relationship between lead exposure and the decreased percentage of normal sperm morphology was mediated by 8-OHdG. Our findings suggest that higher urinary arsenic, cadmium and lead levels were associated with increased oxidative stress markers, which also related with altered semen quality. 8-isoPGF2α and 8-OHdG might be the possible mediators of the associations between urinary heavy metals and total motility, progressive motility or the proportion of normal sperm morphology.

Associations between renal functions and exposure of arsenic and polycyclic aromatic hydrocarbon in adults living near a petrochemical complex

BackgroundThe understanding for the impact of petrochemical pollutants exposure on renal functions is limited. ObjectivesOur study examined the associations between renal functions and pollutants exposure in adult residents living in the vicinity of a petrochemical industry. MethodsWe recruited 2069 adult residents near a big petrochemical complex in Taiwan in 2009–2012, and they were categorized into high exposure (HE) and low exposure (LE) groups based on their address to source by 10 km radius. Study subjects were measured the urinary levels of arsenic, cadmium, mercury, thallium, and 1-hydroxypyrene (1-OHP). The estimated glomerular filtration rate (eGFR) was calculated using the Taiwanese Chronic Kidney Disease Epidemiology Collaboration equation, and the chronic kidney disease (CKD) prevalence and risks were defined according to KDIGO 2012 guidelines. Adjusted generalized linear and logistic regression models were applied to evaluate the associations between petrochemical exposure and renal functions. ResultsSubjects in the HE areas had significantly lower eGFR, higher CKD prevalence, and higher levels of urinary arsenic, cadmium, mercury, thallium and 1-OHP. The closer to complex and high exposure group of study subjects were significantly associated with the decrease in eGFR, higher ORs for CKD and high-intermediate risk of CKD. In addition, the study subjects who had two-fold urinary arsenic and 1-OHP levels were significantly with decreased 0.68 and 0.49 ml/min/1.73 m2 of eGFR, respectively. ConclusionsResiding closer and higher arsenic and polycyclic aromatic hydrocarbon exposure were associated with the renal impairment and risks of CKD among the residential population near the petrochemical industry.