Arsenic Methylation Research Articles

Regulation of transgelin and GST-pi proteins in the tissues of hamsters exposed to sodium arsenite

Regulation of transgelin and GST-pi proteins in the tissues of hamsters exposed to sodium arsenite

Essential hypertension in patients exposed to high-arsenic exposed areas in western China: Genetic susceptibility and urinary arsenic metabolism characteristics

ObjectiveTo clarify the urinary arsenic metabolism characteristics in individuals with essential hypertension and to analyze the relationship between lipid metabolism gene polymorphisms and susceptibility to essential hypertension in individuals in high-arsenic areas in western China. MethodsA case-control study was conducted and involved individuals exposed to high arsenic levels (in this study, the arsenic content in the pressurized well water was 0–510.2 μg/L, and that in the mechanical well water was 167 μg/L) in two adjacent high-arsenic areas in Shanxi Province and the Inner Mongolia Autonomous Region, China. A total of 699 samples were collected, including 192 case samples (patients with hypertension) and 507 control samples (no hypertension). Blood pressure measurement data obtained from an epidemiological survey were used to determine whether the subjects had hypertension, and a logistic regression model was used to analyze the association between lipid metabolism gene polymorphisms and hypertension susceptibility. Blood and urine samples were collected based on epidemiological methods, single nucleotide polymorphisms (SNPs) were genotyped using a SNPscan™ multiple SNP typing kit, and urinary arsenic concentrations were determined using the hydride generation atomic fluorescence method (HG-AFS). ResultsADIPOQ/rs266729 was the dominant genetic model [(GC + GG) vs CC = 0.686:1, 95 % CI = 0.478−0.983], and FABP2/rs1799883 was the recessive genetic model [TT vs (CC + TC) = 1.690:1, 95 % CI = 1.014–2.816]. The distribution of the urinary arsenic secondary methylation ratio (SMR) [dimethylated arsenic (DMA)/monomethylated arsenic (MMA)] was different between hypertensive patients and controls. ConclusionADIPOQ/rs266729 and FABP2/rs1799883 polymorphisms affect susceptibility to essential hypertension in individuals exposed to high levels of arsenic; there was a clear difference in the urinary arsenic metabolism pattern between hypertensive patients and controls.

Regulation of arsenic methylation: identification of the transcriptional region of the human AS3MT gene.

The human enzyme As(III) S-adenosylmethionine methyltransferase (AS3MT) catalyzes arsenic biotransformations and is considered to contribute to arsenic-related diseases. AS3MT is expressed in various tissues and cell types including liver, brain, adrenal gland, and peripheral blood mononuclear cells but not in human keratinocytes, urothelial, or brain microvascular endothelial cells. This indicates that AS3MT expression is regulated in a tissue/cell type-specific manner, but the mechanism of transcriptional regulation of expression of the AS3MT gene is not known. In this study, we define the DNA sequence of the core promoter region of the human AS3MT gene. We identify a GC box in the promoter to which the stress-related transcription factor Sp1 binds, indicating involvement of regulatory elements in AS3MT gene expression.

Arsenic bioaccumulation in the soil fauna alters its gut microbiome and microbial arsenic biotransformation capacity

The biotransformation of arsenic mediated by microorganisms plays an important role in the arsenic biogeochemical cycle. However, the fate and biotransformation of arsenic in different soil fauna gut microbiota are largely unknown. Herein the effects of arsenic contamination on five types of soil fauna were compared by examining variations in arsenic bioaccumulation, gut microbiota, and arsenic biotransformation genes (ABGs). Significant difference was observed in the arsenic bioaccumulation across several fauna body tissues, and Metaphire californica had the highest arsenic bioaccumulation, with a value of 107 ± 1.41 mg kg−1. Arsenic exposure significantly altered overall patterns of ABGs; however, dominant genes involved in arsenic redox and other genes involved in arsenic methylation and demethylation were not significantly changed across animals. Except for M. californica, the abundance of ABGs in other animal guts firstly increased and then decreased with increasing arsenic concentrations. In addition, exposure of soil fauna to arsenic led to shifts in the unique gut-associated bacterial community, but the magnitude of these changes varied significantly across ecological groups of soil fauna. A good correlation between the gut bacterial communities and ABG profiles was observed, suggesting that gut microbiota plays important roles in the biotransformation of arsenic. Overall, these results provide a universal profiling of a microbial community capable of arsenic biotransformation in different fauna guts. Considering the global distribution of soil fauna in the terrestrial ecosystem, this finding broadens our understanding of the hidden role of soil fauna in the arsenic bioaccumulation and biogeochemical cycle.

Effect of atmospheric H2O2 on arsenic methylation and volatilization from rice plants and paddy soil

Studies focusing on arsenic methylation and volatilization in paddy soil, aiming to limit bioaccumulation of arsenic (As) in rice grains, have attracted global attention. In this study, we explored three aspects of these topics. First, rainwater and trace H2O2 were compared for their influence on the arsenic methylation and volatilization of paddy soil in different rice growth stages. Second, the arsenic accumulation in different parts of rice was affected by rainwater and trace H2O2. Third, we determined whether rice fields were affected by rainwater and trace H2O2. The result showed that the rainwater or trace H2O2 irrigation caused As(III) to significantly decrease and As(V) to significantly increase in soil. A similar consequence occurred in the filling stage and mature stage of rice. The arsenic volatilization rates of the rainwater and trace H2O2 irrigation were significantly higher than the control, and the arsenic volatilization of rainwater irrigation was the highest (51.0 μg m−2 d−1) in the filling stage. Compared to the control, the total arsenic and iAs of treatments decreased by 14–41% and 12–32% respectively. Finally, we found that rainwater and trace H2O2 irrigation likely increased rice fields.

Arsenic methylation – Lessons from three decades of research

Between 1990 and 2020, our understanding of the significance of arsenic biomethylation changed in remarkable ways. At the beginning of this period, the conversion of inorganic arsenic into mono- and di-methylated metabolites was viewed primarily as a process that altered the kinetic behavior of arsenic. By increasing the rate of clearance of arsenic, the formation of methylated metabolites reduced exposure to this toxin; that is, methylation was detoxification. By 2020, it was clear that at least some of the toxic effects associated with As exposure depended on formation of methylated metabolites containing trivalent arsenic. Because the trivalent oxidation state of arsenic is associated with increased potency as a cytotoxin and clastogen, these findings were consistent with methylation-related changes in the dynamic behavior of arsenic. That is, methylation was activation. Our current understanding of the role of methylation as a modifier of kinetic and dynamic behaviors of arsenic is the product of research at molecular, cellular, organismic, and population levels. This information provides a basis for refining our estimates of risk associated with long term exposure to inorganic arsenic in environmental media, food, and water. This report summarizes the growth of our knowledge of enzymatically catalyzed methylation of arsenic over this period and considers the prospects for new discoveries.

Nutrition, one-carbon metabolism and arsenic methylation

Exposure to arsenic (As) is a major public health concern globally. Inorganic As (InAs) undergoes hepatic methylation to form monomethyl (MMAs)- and dimethyl (DMAs)-arsenical species, facilitating urinary As elimination. MMAsIII is considerably more toxic than either InAsIII or DMAsV, and a higher proportion of MMAs in urine has been associated with risk for a wide range of adverse health outcomes. Efficiency of As methylation differs substantially between species, between individuals, and across populations. One-carbon metabolism (OCM) is a biochemical pathway that provides methyl groups for the methylation of As, and is influenced by folate and other micronutrients, such as vitamin B12, choline, betaine and creatine. A growing body of evidence has demonstrated that OCM-related micronutrients play a critical role in As methylation. This review will summarize observational epidemiological studies, interventions, and relevant experimental evidence examining the role that OCM-related micronutrients have on As methylation, toxicity of As, and risk for associated adverse health-related outcomes. There is fairly robust evidence supporting the impact of folate on As methylation, and some evidence from case-control studies indicating that folate nutritional status influences risk for As-induced skin lesions and bladder cancer. However, the potential for folate to be protective for other As-related health outcomes, and the potential beneficial effects of other OCM-related micronutrients on As methylation and risk for health outcomes are less well studied and warrant additional research.

Monomethylated arsenic was the Major methylated arsenic in Red blood cells of acute promyelocytic leukemia patients treated with arsenic trioxide

BackgroundArsenic trioxide (ATO) has been successfully applied in the treatment of acute promyelocytic leukemia (APL). Arsenic metabolites including inorganic arsenic and methylated arsenic could lead to different toxicity and curative effect. This study aims to establish a method to determine arsenic species in red blood cells (RBCs), clarify the distribution characteristics of arsenic species in RBCs. MethodsSteady state blood samples were collected from 97 APL patients. H2O2 and HClO4 were used to release the hemoglobin bounding arsenic and precipitate protein. Arsenite (iAsIII), arsenate (iAsV), monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV) in plasma and RBCs were detected by HPLC-HG-AFS. Free and bound arsenic species in RBCs were separated by 30 kDa molecular mass cutoff filters and determined to evaluate hemoglobin binding capacity of different arsenic species. ResultsThe method was validated with accuracy ranged from 84.75% to 104.13%. Arsenic species in RBCs followed the trend iAs > MMA > DMA (p < 0.01), while the concentration of DMA was significantly higher than iAs and MMA in plasma (p < 0.01). The correlation between iAs concentration in plasma and corresponding RBCs arsenic level was weak. And the concentrations of DMA and MMA in plasma were moderately positive correlated with those in RBCs. Hemoglobin-binding ratios of iAs, MMA and DMA were all over 70 %. ConclusionsIn this study, we provided a reliable method to determine arsenic species in RBCs of APL patients treated with ATO by HPLC-HG-AFS. It was confirmed that the concentration of DMA is the highest in plasma, while MMA is the most predominant methylated arsenic in RBCs. High affinity of MMA with human Hb was responsible for the accumulation of arsenic in RBCs of APL patients.

Paracyclops chiltoni inhabiting water highly contaminated with arsenic: Water chemistry, population structure, and arsenic distribution within the organism

We investigated population structure and arsenic bioaccumulation and distribution in zooplankton inhabiting highly contaminated freshwater with arsenic. We collected water and zooplankton samples over a 4 year period, determined environmental temperature as well as water temperature, pH, electrical conductivity (EC), total dissolved solids (TDS), oxidation-reduction potential (ORP), dissolved oxygen (DO), major cations and anions and total arsenic concentration. We identified zooplankton species and determined their abundance, length, sex ratios, and arsenic bioaccumulation and distribution in exposed organisms. At the study site, an extremophile, Paracyclops chiltoni, was found to survive in an environment with high concentration of arsenic, sulfate and fluoride in freshwater as a well-adapted organism. Results showed that the average arsenic concentration in freshwater was 53.64 ± 10.58 mg/L. Exposed organisms of Paracyclops chiltoni showed arsenic accumulation (up to 9.6 ± 5.4 mgAs/kg) in its body, likely in the digestive tract as well as typical abundance and length, which showed a relationship to environmental temperature and oxic conditions in freshwater. Metallotolerant copepods might help to better understand if arsenic methylation processes occur in freshwater aquatic organisms.

Arsenic Exposure, Arsenic Metabolism, and Glycemia: Results from a Clinical Population in New York City.

Little information is available regarding the glycemic effects of inorganic arsenic (iAs) exposure in urban populations. We evaluated the association of total arsenic and the relative proportions of arsenic metabolites in urine with glycemia as measured by glycated blood hemoglobin (HbA1c) among 45 participants with prediabetes (HbA1c ≥ 5.7–6.4%), 65 with diabetes (HbA1c ≥ 6.5%), and 36 controls (HbA1c < 5.7%) recruited from an academic medical center in New York City. Each 10% increase in the proportion of urinary dimethylarsinic acid (DMA%) was associated with an odds ratio (OR) of 0.59 (95% confidence interval (CI): 0.28–1.26) for prediabetes, 0.46 (0.22–0.94) for diabetes, and 0.51 (0.26–0.99) for prediabetes and diabetes combined. Each 10% increase in the proportion of urinary monomethylarsonic acid (MMA%) was associated with a 1.13% (0.39, 1.88) increase in HbA1c. In contrast, each 10% increase in DMA% was associated with a 0.76% (0.24, 1.29) decrease in HbA1c. There was no evidence of an association of total urinary arsenic with prediabetes, diabetes, or HbA1c. These data suggest that a lower arsenic methylation capacity indicated by higher MMA% and lower DMA% in urine is associated with worse glycemic control and diabetes. Prospective, longitudinal studies are needed to evaluate the glycemic effects of low-level iAs exposure in urban populations.

Rare, Protein-Altering Variants in AS3MT and Arsenic Metabolism Efficiency: A Multi-Population Association Study.

Background:Common genetic variation in the arsenic methyltransferase (AS3MT) gene region is known to be associated with arsenic metabolism efficiency (AME), measured as the percentage of dimethylarsinic acid (DMA%) in the urine. Rare, protein-altering variants in AS3MT could have even larger effects on AME, but their contribution to AME has not been investigated.Objectives:We estimated the impact of rare, protein-coding variation in AS3MT on AME using a multi-population approach to facilitate the discovery of population-specific and shared causal rare variants.Methods:We generated targeted DNA sequencing data for the coding regions of AS3MT for three arsenic-exposed cohorts with existing data on arsenic species measured in urine: Health Effects of Arsenic Longitudinal Study (HEALS, ), Strong Heart Study (SHS, ), and New Hampshire Skin Cancer Study (NHSCS, ). We assessed the collective effects of rare (allele frequency ), protein-altering AS3MT variants on DMA%, using multiple approaches, including a test of the association between rare allele carrier status (yes/no) and DMA% using linear regression (adjusted for common variants in 10q24.32 region, age, sex, and population structure).Results:We identified 23 carriers of rare-protein-altering AS3MT variant across all cohorts (13 in HEALS and 5 in both SHS and NHSCS), including 6 carriers of predicted loss-of-function variants. DMA% was 6–10% lower in carriers compared with noncarriers in HEALS [ (95% CI: , )], SHS [ (95% CI: , )], and NHSCS [ (95% CI: , )]. In meta-analyses across cohorts, DMA% was 8.7% lower in carriers [ (95% CI: , )].Discussion:Rare, protein-altering variants in AS3MT were associated with lower mean DMA%, an indicator of reduced AME. Although a small percentage of the population (0.5–0.7%) carry these variants, they are associated with a 6–10% decrease in DMA% that is consistent across multiple ancestral and environmental backgrounds. https://doi.org/10.1289/EHP8152

The level of exposure affects the arsenic urinary methylation profile of a population of children

Differences in the As methylation capacity of Argentine children, exposed to different levels of As in drinking water were evaluated, considering the gender and the presence of the As3MT T860C gene polymorphism. Inorganic As (%IAs), monomethylated As (%MMA) and dimethylated As (%DMA), primary methylation index (PMI) and secondary methylation index (SMI) were evaluated and represented the As methylation capacity. Urinary As ranged from 18 to 5106 µg/g creatinine. Comparisons were performed between lowest and highest quartiles of urinary As. The level of exposure was positively related to urinary %MMA and negatively to %DMA and to SMI. Considering the presence of the As3MT T860C polymorphism, the level of exposure increased %MMA, and decreased %DMA and the SMI in carriers of the T/T genotype. SMI OR for T/T carriers was 10.61 (95% CI: 2.16–52.16, p: 0.0036). Regarding the gender, the level of exposure increased %MMA, and decreased %DMA and the SMI in girls and boys. SMI OR for girls was 8.71 (95% CI: 1.48–51.08, p: 0.0165) and for boys, OR: 18.15 (95% CI: 2.03–162.35, p: 0.0095). It was possible to identify the level of exposure as a factor that can modify the influence that other factors have on the methylation of As.

Dietary intake and urinary excretion of methylated arsenicals of Japanese adults consuming marine foods and rice

ABSTRACT Dietary intake and urinary excretion of monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and arsenobetaine (AsB) were measured in 150 adult Japanese subjects. Duplicate diet (DD) samples and first void of urine on the next morning of DD sampling day were collected and analysed for arsenic species with liquid chromatography-ICP mass spectrometry. Median (min-max) intakes of MMA, DMA and AsB were <2.3 (<2.3-<2.3), 4.57 (<2.3–24.3), and 13.6 (<2.4–231) μg As/day, respectively, and median urinary concentrations were 1.90 (<0.37–26.), 21.9 (<0.27–141) and 19.6 (<0.37–1063) ng As/mg creatinine, respectively. Interrelationships between intake levels and urinary concentrations were mostly significant with positive coefficients indicating mutual association due to co-exposure, metabolism and/or dietary habit. Urinary concentrations and intake levels of AsB were also positively correlated confirming the applicability of urine analysis as biomarker of exposure. The present descriptive results provide with essential piece of information in assessing health risk of methylated arsenicals for population who consume marine products and rice.

Urinary arsenic species and methylation efficiency during pregnancy: Concentrations and associated factors in Spanish pregnant women

BackgroundArsenic (As) is considered to be toxic for humans, the main routes of exposure being through drinking water and the diet. Once ingested, inorganic arsenic can be methylated sequentially to monomethyl and dimethyl arsenicals. Several factors can affect both As exposure and methylation efficiency. ObjectivesTo describe the urinary concentrations of the different As species and evaluate the methylation efficiency during pregnancy, as well as their associated factors in a birth cohort of pregnant Spanish women. MethodsParticipants in this cross-sectional study were 1017 pregnant women from two areas of Spain who had taken part in the INMA (Environment and Childhood) project (2003–2008). Total As (organic and inorganic compounds) and its main metabolites (monomethylarsonic acid, [MMA], dimethylarsinic acid, [DMA], inorganic As [iAs]) and arsenobetaine [AB]) were measured in urine samples collected during the first trimester. Sociodemographic and dietary information was collected through questionnaires. Multivariate linear regression models were used to explore the association between As species concentrations and covariates. Arsenic methylation efficiency was determined through the percentages of the metabolites and using As methylation phenotypes, obtained from principal component analysis. ResultsMedian urine concentrations were 33.0, 21.6, 6.5, 0.35 and 0.33 μg/g creatinine for total As, AB, DMA, MMA and iAs, respectively. Daily consumption of rice and seafood during the first trimester of pregnancy were positively associated with the concentration of As species (i.e., β [CI95%] = 0.36 [0.09, 0.64] for rice and iAs, and 1.06 [0.68, 1.44] for seafood and AB). TAs, AB and iAs concentrations, and DMA and MMA concentrations were associated with legume and vegetable consumption, respectively. The medians of the percentage of As metabolites were 89.7 for %DMA, 5.1 for %MMA and 4.7 for %iAs. Non-smoker women and those with higher body mass index presented a higher methylation efficiency (denoted by a higher %DMA and lower %MMA). DiscussionCertain dietary, lifestyle, and environmental factors were observed to have an influence on both As species concentrations and methylation efficiency in our population. Further birth cohort studies in low exposure areas are necessary to improve knowledge about arsenic exposure, especially to inorganic forms, and its potential health impact during childhood.

Importance of monitoring arsenic methylation metabolism in acute promyelocytic leukemia patients receiving the treatment of arsenic trioxide

BackgroundArsenic trioxide [ATO, inorganic arsenite (iAsIII) in solution] plays an important role in the treatment of acute promyelocytic leukemia (APL). However, the long-term adverse effects (AEs) and the retention of arsenic among APL patients are rarely reported. In this study, we focused on arsenic methylation metabolism and its relationship with chronic hepatic toxicity, as we previously reported, among APL patients who had finished the treatment of ATO.MethodsA total of 112 de novo APL patients who had completed the ATO-containing treatment were enrolled in the study. Arsenic species [iAsIII, inorganic arsenate (iAsV), and their organic metabolites, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)] in patients’ plasma, urine, hair and nails were detected by high-performance liquid chromatography combined with inductively coupled plasma mass spectrometry (HPLC-ICP-MS). Eighteen single nucleotide polymorphisms (SNPs) of the arsenic (+ 3 oxidative state) methylation transferase (AS3MT) gene, which was known as the main catalyzer for arsenic methylation, were tested with the polymerase chain reaction method.ResultsThe study showed the metabolic pattern of arsenic in APL patients undergoing and after the treatment of ATO, in terms of total arsenic (TAs) and four species of arsenic. TAs decreased to normal after 6 months since cessation of ATO. But the arsenic speciation demonstrated significantly higher portion of iAsIII in patient’s urine (40.08% vs. 1.94%, P < 0.001), hair (29.25% vs. 13.29%, P = 0.002) and nails (30.21% vs. 13.64%, P = 0.003) than the healthy controls’, indicating a decreased capacity of arsenic methylation metabolism after the treatment of ATO. Urine primary methylation index (PMI) was significantly lower in patients with both chronic liver dysfunction (0.14 vs. 0.28, P = 0.047) and hepatic steatosis (0.19 vs. 0.3, P = 0.027), suggesting that insufficient methylation of arsenic might be related to chronic liver disorders. Two SNPs (A9749G and A27215G) of the AS3MT gene were associated with impaired urine secondary methylation index (SMI).ConclusionsThe long-term follow-up of arsenic speciation indicated a decreased arsenic methylation metabolism and a probable relationship with chronic hepatic disorders among APL patients after the cessation of ATO. Urine PMI could be a monitoring index for chronic AEs of ATO, and the SNPs of AS3MT gene should be considered when determining the dosage of ATO.

Association between body mass index and arsenic methylation in three studies of Bangladeshi adults and adolescents

BackgroundWater-borne arsenic (As) exposure is a global health problem. Once ingested, inorganic As (iAs) is methylated to mono-methyl (MMA) and dimethyl (DMA) arsenicals via one-carbon metabolism (OCM). People with higher relative percentage of MMA (MMA%) in urine (inefficient As methylation), have been shown to have a higher risk of cardiovascular disease and several cancers but appear to have a lower risk of diabetes and obesity in populations from the US, Mexico, and Taiwan. It is unknown if this opposite pattern with obesity is present in Bangladesh, a country with lower adiposity and higher As exposure in drinking water. ObjectiveTo characterize the association between body mass index (BMI) and As methylation in Bangladeshi adults and adolescents participating in the Folic Acid and Creatine Trial (FACT); Folate and Oxidative Stress (FOX) study; and Metals, Arsenic, and Nutrition in Adolescents Study (MANAS). MethodsArsenic species (iAs, MMA, DMA) were measured in urine and blood. Height and weight were measured to calculate BMI. The associations between concurrent BMI with urine and blood As species were analyzed using linear regression models, adjusting for nutrients involved in OCM such as choline. In FACT, we also evaluated the prospective association between weight change and As species. ResultsMean BMIs were 19.2/20.4, 19.8/21.0, and 17.7/18.7 kg/m2 in males/females in FACT, FOX, and MANAS, respectively. BMI was associated with As species in female but not in male participants. In females, after adjustment for total urine As, age, and plasma folate, the adjusted mean differences (95% confidence) in urinary MMA% and DMA% for a 5 kg/m2 difference in BMI were −1.21 (−1.96, −0.45) and 2.47 (1.13, 3.81), respectively in FACT, −0.66 (−1.56, 0.25) and 1.43 (−0.23, 3.09) in FOX, and −0.59 (−1.19, 0.02) and 1.58 (−0.15, 3.30) in MANAS. The associations were attenuated after adjustment for choline. Similar associations were observed with blood As species. In FACT, a 1-kg of weight increase over 2 to 10 (mean 5.4) years in males/females was prospectively associated with mean DMA% that was 0.16%/0.19% higher. DiscussionBMI was negatively associated with MMA% and positively associated with %DMA in females but not males in Bangladesh; associations were attenuated after plasma choline adjustment. These findings may be related to the role of body fat on estrogen levels that can influence one-carbon metabolism, e.g. by increasing choline synthesis. Research is needed to determine whether the associations between BMI and As species are causal and their influence on As-related health outcomes.

Urinary total arsenic and arsenic methylation capacity in pregnancy and gestational diabetes mellitus: A case-control study

Previous studies suggest arsenic exposure may increase the risk of gestational diabetes mellitus (GDM). However, prior assessments of total arsenic concentrations have not distinguished between toxic and nontoxic species. Our study aimed to investigate the relationships between inorganic arsenic exposure, arsenic methylation capacity, and GDM.Sixty-four cases of GDM and 237 controls were analyzed for urinary concentrations of inorganic arsenic species and their metabolites (arsenite (As3), arsenate (As5), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)), and organic forms of arsenic. Inorganic arsenic exposure was defined as the sum of inorganic and methylated arsenic species (iSumAs). Methylation capacity indices were calculated as the percentage of inorganic arsenic species [iAs% = (As3 + As5)/iSumAs, MMA% = MMA/iSumAs, and DMA% = DMA/iSumAs]. Multivariable logistic regression was performed to evaluate the association between inorganic arsenic exposure, methylation capacity indices, and GDM.We did not observe evidence of a positive association between iSumAs and GDM. However, women with GDM had an increased odds of inefficient methylation capacity when comparing the highest and lowest tertiles of iAs% (adjusted odds ratio (aOR) = 1.48, 95% CI 0.58–3.77) and MMA% (aOR = 1.95 (95% CI 0.81–4.70) and a reduced odds of efficient methylation capacity as indicated by DMA% (aOR = 0.62 (95% CI 0.25–1.52), though the confidence intervals included the null value.While the observed associations with arsenic methylation indices were imprecise and warrant cautious interpretation, the direction and magnitude of the relative measures reflected a pattern of lower detoxification of inorganic arsenic exposures among women with GDM.

Diverse genetic backgrounds play a prominent role in the metabolic phenotype of CC021/Unc and CC027/GeniUNC mice exposed to inorganic arsenic

Arsenic methyltransferase (AS3MT) is the key enzyme in the pathway for the methylation of inorganic arsenic (iAs), a potent human carcinogen and diabetogen. AS3MT converts iAs to mono- and dimethylated arsenic species (MAs, DMAs) that are excreted mainly in urine. Polymorphisms in AS3MT is a key genetic factor affecting iAs metabolism and toxicity. The present study examined the role of As3mt polymorphisms in the susceptibility to the diabetogenic effects of iAs exposure using two Collaborative Cross mouse strains, CC021/Unc and CC027/GeniUnc, carrying different As3mt haplotypes. Male mice from the two strains were exposed to iAs in drinking water (0, 0.1 or 50 ppm) for 11 weeks. Blood glucose and plasma insulin levels were measured after 6-h fasting and 15 min after i.p. injection of glucose. Body composition was determined using magnetic resonance imaging. To asses iAs metabolism, the concentrations of iAs, MAs and DMAs were measured in urine. The results show that CC021 mice, both iAs-exposed and controls, had higher body fat percentage, lower fasting blood glucose, higher fasting plasma insulin, and were more insulin resistant than their CC027 counterparts. iAs exposure had a minor effect on diabetes indicators and only in CC027 mice. Blood glucose levels 15 min after glucose injection were significantly higher in CC027 mice exposed to 0.1 ppm iAs than in control mice. No significant differences were found in the concentrations or proportions of arsenic species in urine of CC021 and CC027 mice at the same exposure level. These results suggest that the differences in As3mt haplotypes did not affect the profiles of iAs or its metabolites in mouse urine. The major differences in diabetes indicators were associated with the genetic backgrounds of CC021 and CC027 mice. The effects of iAs exposure, while minor, were genotype- and dose-dependent.

Nutrition, one-carbon metabolism and arsenic methylation in Bangladeshi adolescents

BackgroundOver 57 million people in Bangladesh are chronically exposed to arsenic-contaminated drinking water. Ingested inorganic arsenic (InAs) undergoes hepatic methylation generating monomethyl- (MMAs) and dimethyl- (DMAs) arsenic species in a process that facilitates urinary As (uAs) elimination. One-carbon metabolism (OCM), a biochemical pathway that is influenced by folate and vitamin B12, facilitates the methylation of As. OCM also supports nucleotide and amino acid synthesis, particularly during periods of rapid growth such as adolescence. While folate supplementation increases As methylation and lowers blood As (bAs) in adults, little data is available for adolescents. ObjectivesTo examine the associations between OCM-related micronutrients and As methylation in Bangladeshi adolescents chronically exposed to As-contaminated drinking water. MethodsWe conducted a cross-sectional study of 679 Bangladeshi adolescents, including 320 boys and 359 girls aged 14–16 years. Nutritional status was assessed by red blood cell (RBC) folate, plasma folate, plasma B12 and homocysteine (Hcys). Arsenic-related outcomes included blood arsenic (bAs), urinary arsenic (uAs), and urinary arsenic metabolites expressed as a percentage of total urinary As: %InAs, %MMAs, %DMAs. ResultsBoys had significantly lower B12, higher Hcys, higher bAs, higher uAs, higher %MMAs, and a trend toward lower RBC folate compared to girls. Therefore, regression analyses controlling for water As and BMI were sex stratified. Among girls, RBC folate was inversely associated with bAs, plasma B12 was inversely associated with uAs, and plasma Hcys was inversely associated with %MMA. Among boys, plasma folate was inversely associated with %InAs and positively associated with %DMA, RBC folate was inversely associated with %InAs and positively associated with %MMA, while Hcys was positively associated with %InAs. ConclusionsThese findings suggest that associations between OCM nutritional status, bAs, and distribution of As metabolites in adolescents are similar to previously reported observations in adults and in children. The As methylation findings are statistically significant among boys but not among girls; this may be related to estrogen which more strongly influences OCM in females. The inverse association between Hcys and %MMA in girls is somewhat unexpected given that Hcys is known to be an indicator of impaired OCM and low folate/B12 in adults. Overall, these results indicate that the associations between OCM-related micronutrients and arsenic methylation in adolescents are generally similar to prior findings in adults, though these associations may differ by sex. Additionally, these findings suggest that more investigation into the role of Hcys in adolescent physiology is needed, perhaps particularly for girls. Additional studies are needed to evaluate the impact of OCM and As methylation on As-related adverse health outcomes (such as cancer and cardiovascular disease) in people exposed to As during adolescence.

Increase in arsenic methylation and volatilization during manure composting with biochar amendment in an aeration bioreactor

Biochar is widely used as an amendment to optimize the composting process. In this study, we firstly investigated the effects of biochar amendment on methylation and volatilization of arsenic (As), and the microbial communities during manure composting. Biochar amendment was found to increase the concentrations of monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) during mesophilic (days 0–10) and early thermophilic (days 11–15) phases, and promote As volatilization during the maturing phase (days 60–80) of composting. In addition, the abundances of As(V) reductase (arsC) and As(III) S-adenosyl-L-methionine methyltransferase (arsM) genes were higher in the biochar treatment than that in the control. Moreover, biochar amendment influenced the microbial communities by promoting As methylation and volatilization via Ensifer and Sphingobium carrying arsC genes, and Rhodopseudomonas and Pseudomonas carrying arsM genes. This study emphasized the considerable role of biochar on methylation and volatilization of As during manure composting and provided an overall characterization of the community compositions of arsC and arsM genes during manure composting. It will broaden our insights in As biogeochemical cycle during manure composting with biochar amendment, which will facilitate the regulation of As during manure composting and its application in agricultural soil.