Soil redox status governs within-field spatial variation in microbial arsenic methylation and rice straighthead disease.

Microbial arsenic (As) methylation in paddy soil produces mainly dimethylarsenate (DMA), which can cause physiological straighthead disease in rice. The disease is often highly patchy in the field, but the reasons remain unknown. We investigated within-field spatial variations in straighthead disease severity, As species in rice husks and in soil porewater, microbial composition and abundance of arsM gene encoding arsenite S-adenosylmethionine methyltransferase in two paddy fields. The spatial pattern of disease severity matched those of soil redox potential, arsM gene abundance, porewater DMA concentration, and husk DMA concentration in both fields. Structural equation modelling identified soil redox potential as the key factor affecting arsM gene abundance, consequently impacting porewater DMA and husk DMA concentrations. Core amplicon variants that correlated positively with husk DMA concentration belonged mainly to the phyla of Chloroflexi, Bacillota, Acidobacteriota, Actinobacteriota, and Myxococcota. Meta-omics analyses of soil samples from the disease and non-disease patches identified 5129 arsM gene sequences, with 71% being transcribed. The arsM-carrying hosts were diverse and dominated by anaerobic bacteria. Between 96 and 115 arsM sequences were significantly more expressed in the soil samples from the disease than from the non-disease patch, which were distributed across 18 phyla, especially Acidobacteriota, Bacteroidota, Verrucomicrobiota, Chloroflexota, Pseudomonadota, and Actinomycetota. This study demonstrates that even a small variation in soil redox potential within the anoxic range can cause a large variation in the abundance of As-methylating microorganisms, thus resulting in within-field variation in rice straighthead disease. Raising soil redox potential could be an effective way to prevent straighthead disease.

Associations of arsenic exposure and arsenic metabolism with the risk of non-alcoholic fatty liver disease.

Growing evidences supported that arsenic exposure contributes to non-alcoholic fatty liver disease (NAFLD) risk, but findings were still inconsistent. Additionally, once absorbed, arsenic is methylated into monomethyl and dimethyl arsenicals. However, no studies investigated the association of arsenic metabolism with NAFLD. Our objectives were to evaluate the associations of arsenic exposure and arsenic metabolism with NAFLD prevalence. We conducted a case-control study with 1790 participants derived from Dongfeng-Tongji cohort and measured arsenic species (arsenite, arsenate, monomethylarsonate [MMA], dimethylarsinate [DMA], and arsenobetaine) in urine. Arsenic exposure (∑As) was defined as the sum of inorganic arsenic (iAs), MMA, and DMA. Arsenic metabolism was evaluated as the proportions of inorganic-related species (iAs%, MMA%, and DMA%) and methylation efficiency ratios (primary methylation index [PMI], secondary methylation index [SMI]). NAFLD was diagnosed by liver ultrasound. Logistic regression was used to evaluate the associations. The median of ∑As was 13.24 µg/g creatinine. The ∑As showed positive and nonlinear association with moderate/severe NAFLD (OR: per log-SD = 1.33, 95% CI: [1.03,1.71]; Pfor nonlinearity = 0.021). The iAs% (OR: per SD = 1.16, 95% CI: [1.03,1.30]) and SMI (OR: per log-SD = 1.16, 95% CI: [1.03,1.31]) showed positive while MMA% (OR: per SD = 0.80, 95% CI: [0.70,0.91]) and PMI (OR: per log-SD = 0.86, 95% CI: [0.77,0.96]) showed inverse associations with NAFLD. Moreover, the ORs (95% CI) of NAFLD for each 5% increase in iAs% was 1.36 (1.17,1.58) when MMA% decreased and 1.07 (1.01,1.13) when DMA% decreased; and for each 5% increase in MMA%, it was 0.74 (0.63,0.86) and 0.79 (0.69,0.91) when iAs% and DMA% decreased, respectively. The results suggest that inorganic arsenic exposure is positively associated with NAFLD risk and arsenic methylation efficiency plays a role in the NAFLD. The findings provide clues to explore potential interventions for the prevention of NAFLD. Prospective studies are needed to validate our findings.

Dimethylmonothioarsinic acid (DMMTAV) differentially modulates the expression of AHR-regulated cytochrome P450 1A enzymes in vivo and in vitro.

Dimethylmonothioarsinic acid (DMMTAV), a pentavalent thio-arsenic derivative, has been found in bodily fluids and tissues including urine, liver, kidney homogenates, plasma, and red blood cells. Although DMMTAV is a minor metabolite in humans and animals, its substantial toxicity raises concerns about potential carcinogenic effects. This toxicity could be attributed to arsenicals' ability to regulate cytochrome P450 1 A (CYP1A) enzymes, pivotal in procarcinogen activation or detoxification. The current study investigates DMMTAV's impact on CYP1A1/2 expression, individually and in conjunction with its inducer, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). C57BL/6 mice were intraperitoneally injected with 6 mg/kg DMMTAV, alone or with 15 µg/kg TCDD, for 6 and 24 h. Similarly, Hepa-1c1c7 cells were exposed to DMMTAV (0.5, 1, and 2 µM) with or without 1 nM TCDD for 6 and 24 h. DMMTAV hindered TCDD-induced elevation of Cyp1a1 mRNA, both in vivo (at 6 h) and in vitro, associated with reduced CYP1A regulatory element activation. Interestingly, in C57BL/6 mice, DMMTAV boosted TCDD-induced CYP1A1/2 protein and activity, unlike Hepa-1c1c7 cells where it suppressed both. DMMTAV co-exposure increased TCDD-induced Cyp1a2 mRNA. While Cyp1a1 mRNA stability remained unchanged, DMMTAV negatively affected protein stability, indicated by shortened half-life. Baseline levels of CYP1A1/2 mRNA, protein, and catalytic activities showed no significant alterations in DMMTAV-treated C57BL/6 mice and Hepa-1c1c7 cells. Taken together, these findings indicate, for the first time, that DMMTAV differentially modulates the TCDD-mediated induction of AHR-regulated enzymes in both liver of C57BL/6 mice and murine Hepa-1c1c7 cells suggesting that thio-arsenic pentavalent metabolites are extremely reactive and could play a role in the toxicity of arsenic.

Disturbed nutrient accumulation and cell wall metabolism in panicles are responsible for rice straighthead disease.

Rice straighthead disease substantially reduces crop yield, posing a significant threat to global food security. Dimethylarsinic acid (DMA) is the causal agent of straighthead disease and is highly toxic to the reproductive tissue of rice. However, the precise physiological mechanism underlying DMA toxicity remains unknown. In this study, six rice varieties with varying susceptibility to straighthead were utilized to investigate the growth performance and element distribution in rice panicles under DMA stress through pot experiments, as well as to explore the physiological response to DMA using transcriptomic methods. The findings demonstrate significant variations in both DMA accumulation and straighthead sensitivity among cultivars. The susceptible varieties exhibited higher DMA accumulation indices and displayed typical symptoms of straighthead disease, including erect panicles, deformed rachides and husks, and reduced seed setting rate and grain yield when compared to the resistant varieties. Moreover, DMA addition promoted mineral nutrients to accumulate in rachides and husks but less in grains. DMA showed preferential accumulation in rice grains with a distribution pattern similar to that of Copper (Cu) and zinc (Zn) within the panicle. Transcriptome analyses underscored the substantial impact of DMA on gene expression related to mineral metabolism. Notably, DMA addition significantly up-regulated the expression of pectin methylesterase, pectin lyase, polygalacturonase, and exogalacturonase genes in Nanjingxiangzhan, while these genes were down-regulated or weakly expressed in Ruanhuayou 1179. The alteration of pectin metabolic pathways induced by DMA may lead to abnormality of cell wall assembly and modification, thereby resulting in deformed rice panicles.

Translocation, enzymatic reduction and toxicity of dimethylarsenate in rice.

Dimethylarsenate [DMAs(V)] can be produced by some soil microorganisms through methylation of inorganic arsenic (As), especially in anoxic paddy soils. DMAs(V) is more phytotoxic than inorganic As and can cause the physiological disorder straighthead disease in rice. Rice cultivars vary widely in the resistance to DMAs(V), but the mechanism remains elusive. Here, we investigated the differences in DMAs(V) uptake, translocation, and reduction to dimethylarsenite [DMAs(III)], as well as the effects on the metabolome, between two rice cultivars Mars and Zhe733. We found that Mars was 11-times more resistant to DMAs(V) than Zhe733. Mars accumulated more DMAs(V) in the roots, whereas Zhe733 translocated more DMAs(V) to the shoots and reduced more DMAs(V) to DMAs(III). DMAs(III) was more toxic than DMAs(V). Using heterologous expression and in vitro enzyme assays, we showed that the glutathione-S-transferases OsGSTU17 and OsGSTU50 were able to reduce DMAs(V) to DMAs(III). The expression levels of OsGSTU17 and OsGSTU50 were higher in the shoot of Zhe733 compared to Mars. Metabolomic analysis in rice shoots showed that glutathione (GSH) metabolism was perturbed by DMAs(V) toxicity in Zhe733. Application of exogenous GSH significantly alleviated the toxicity of DMAs(V) in Zhe733. Taken together, the results suggest that Mars is more resistant to DMAs(V) than Zhe733 because of a lower root-to-shoot translocation and a smaller capacity to reduce DMAs(V) to DMAs(III).

Biodilution of Organic Species of Arsenic in Freshwater Food Webs.

Arsenic can accumulate in freshwater biota, sometimes reaching potentially harmful levels. However, the toxicity of arsenic strongly depends on which arsenic species are present. Although organic species are considered less harmful than inorganic ones, they have not been extensively studied in freshwater environments, and drivers of variation in arsenic speciation among sites and taxa remain unclear. We assessed concentrations of two organic arsenic species, arsenobetaine (AsB) and dimethylarsinic acid (DMA), in fish and invertebrates from three lakes near Sudbury, Ontario, Canada-a region with widespread mining impacts. Both AsB and DMA were detected in most samples (n = 212), varying across a wide range of concentrations (<0.001-30.144 and <0.006-5.262 mg/kg dry wt, respectively). The lake with the most severe mining impacts typically had the highest concentrations (designated by square brackets []) of AsB and DMA. In contrast, the percentage of total arsenic made up by AsB (%AsB) and DMA (%DMA) did not vary significantly between lakes. Arsenic speciation in fish muscle varied with fish size, selenium concentrations, and trophic elevation (inferred from nitrogen stable isotope ratios δ15N), but relationships with dietary carbon source (inferred from carbon stable isotope ratios δ13C) were more varied. Within all three lake food webs, [AsB] and [DMA] typically underwent biodilution, decreasing with trophic elevation (i.e., δ15N). Although the aforementioned factors explained some variation in arsenic speciation, there remains considerable unexplained variation. Further studies on arsenic speciation in freshwater biota should target a wider diversity of taxa to better understand drivers of variation in arsenic speciation. In addition, research emphasizing the percentage of inorganic arsenic and other organic arsenic species is needed to improve environmental and human health risk assessments. Environ Toxicol Chem 2024;43:833-846. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

In Planta Arsenic Thiolation in Rice and Arabidopsis thaliana.

Inorganic and methylated thioarsenates have recently been reported to form in paddy soil pore waters and accumulate in rice grains. Among them, dimethylmonothioarsenate (DMMTA) is particularly relevant because of its high cytotoxicity and potential misidentification as nonregulated dimethylarsenate (DMA). Studying DMMTA uptake and flag leaf, grain, and husk accumulation in rice plants during grain filling, substantial dethiolation to DMA was observed with only 8.0 ± 0.1, 9.1 ± 0.6, and 1.4 ± 0.2% DMMTA remaining, respectively. More surprisingly, similar shares of DMMTA were observed in control experiments with DMA, indicating in planta DMA thiolation. Exposure of different rice seedling varieties to not only DMA but also to arsenite and monomethylarsenate (MMA) revealed in planta thiolation as a common process in rice. Up to 35 ± 7% DMA thiolation was further observed in the shoots and roots of the model plant Arabidopsis thaliana. Parameters determining the ratio and kinetics of thiolation versus dethiolation are unknown, yet, but less DMA thiolation in glutathione-deficient mutants compared to wild-type plants suggested glutathione concentration as one potential parameter. Our results demonstrate that pore water is not the only source for thioarsenates in rice grains and that especially the currently nonregulated DMA needs to be monitored as a potential precursor of DMMTA formation inside rice plants.

Genetic Susceptibility to Neurotoxicity Related to Prenatal Inorganic Arsenic Exposure in Young Spanish Children.

We explored the influence of child and maternal single nucleotide polymorphisms (SNPs) in genes related to neurological function and arsenic metabolism (i.e., ABCA1, ABCB1, PON1, CYP3A, BDNF, GSTP1, MT2A, and APOE as well as AS3MT) on the association between prenatal arsenic (As) exposure and methylation efficiency and neuropsychological development in 4-5-year-old children. Participants were 549 mother-child pairs from the INMA (Environment and Childhood) Spanish Project. We measured inorganic arsenic (iAs) and the metabolites monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in urine samples collected during pregnancy. Neuropsychological development was assessed at the age of 4-5 years using the McCarthy Scales of Children's Abilities (MSCA). Several SNPs were determined in maternal and child DNA; AS3MT and APOE haplotypes were inferred. The median ∑As (sum of iAs, DMA, and MMA) was 7.08 µg/g creatinine. Statistically significant interactions for children's APOE haplotype were observed. Specifically, ε4-carrier children had consistently lower MSCA scores in several scales with increasing ∑As and MMA concentrations. These results provide evidence regarding the neurotoxic effects of early life exposure to As, observing that the APOE ε4 allele could make children more vulnerable to this exposure.

The crucial elements for lettuce (Lactuca sativa L.) growth under DMA stress and the linkage with DMA behavior: A new application of ionome.

Dimethylarsinic acid (DMA) is one of the common arsenic (As) species present in soil and is more toxic to plants than others. Identifying the crucial elements for plant growth under DMA stress is essential to enhance plant tolerance to DMA. Herein, we provided for the first time an ionome-based approach to address this issue. The phenotype, As species and concentrations of 11 essential elements in lettuce tissues were monitored under exposures of 0.1, 0.5, 1, 2, 5 mg L-1 DMA in hydroponic culture for 32 days. Lettuces remained normal (no significant difference in phenotype from the control) under 0.1-2 mg L-1 DMA stress, and were inhibited with fresh weights of leaf and root under 5 mg L-1 DMA stress. Integrating the difference in ionome profiles between the two growth states (normal and inhibited) and the responses of the individual element, Mg and S were clarified as the most possible candidates for the crucial elements for lettuce growth under DMA stress. Under 5 mg L-1 DMA stress, the accumulation of Mg and S declined, yet their BCF values were significantly increased, which was consistent with the change in BCF of DMA. Based on the physiological functions of Mg and S and the toxicity of DMA, it could be inferred that the enhanced transfer of Mg and S to leaves should be induced by the potential damage caused by the increased DMA accumulation in leaves, and would result in a shortage of both elements in roots as well as the growth inhibition.

Methylotrophic methanogens and bacteria synergistically demethylate dimethylarsenate in paddy soil and alleviate rice straighthead disease.

Microorganisms play a key role in arsenic (As) biogeochemistry, transforming As species between inorganic and organic forms and different oxidation states. Microbial As methylation is enhanced in anoxic paddy soil, producing primarily dimethylarsenic (DMAs), which can cause rice straighthead disease and large yield losses. DMAs can also be demethylated in paddy soil, but the microorganisms driving this process remain unclear. In this study, we showed that the enrichment culture of methylotrophic methanogens from paddy soil demethylated pentavalent DMAs(V) efficiently. DMAs(V) was reduced to DMAs(III) before demethylation. 16S rRNA gene diversity and metagenomic analysis showed that Methanomassiliicoccus dominated in the enrichment culture, with Methanosarcina and Methanoculleus also being present. We isolated Methanomassiliicoccus luminyensis CZDD1 and Methanosarcina mazei CZ1 from the enrichment culture; the former could partially demethylate trivalent DMAs(III) but not DMAs(V) and the latter could demethylate neither. Addition of strain CZDD1 to the enrichment culture greatly accelerated DMAs(V) demethylation. Demethylation of DMAs(V) in the enrichment culture was suppressed by ampicillin, suggesting the involvement of bacteria. We isolated three anaerobic bacterial strains including Clostridium from the enrichment culture, which could produce hydrogen and reduce DMAs(V) to DMAs(III). Furthermore, augmentation of the Methanomassiliicoccus-Clostridium coculture to a paddy soil decreased DMAs accumulation by rice and alleviated straighthead disease. The results reveal a synergistic relationship whereby anaerobic bacteria reduce DMAs(V) to DMAs(III) for demethylation by Methanomassiliicoccus and also produce hydrogen to promote the growth of Methanomassiliicoccus; enhancing their populations in paddy soil can help alleviate rice straighthead disease.

Dimethylarsinic acid induces bladder carcinogenesis via the amphiregulin pathway.

Dimethylarsinic acid (DMA) is a major metabolite in the urine of humans and rats exposed to inorganic arsenicals, and is reported to induce rat bladder carcinogenesis. In the present study, we focused on early pathways of carcinogenesis triggered by DMA that were also active in tumors. RNA expression in the bladder urothelium of rats treated with 0 and 200 ppm DMA in the drinking water for 4 weeks and in bladder tumors of rats treated with 200 ppm DMA for 2 years was initially examined using microarray analysis and Ingenuity Pathway Analysis (IPA). Expression of 160 genes was altered in both the urothelium of rats treated for 4 weeks with DMA and in DMA-induced tumors. IPA associated 36 of these genes with liver tumor diseases. IPA identified the amphiregulin (Areg)-regulated pathway as a Top Regulator Effects Network. Therefore, we focused on Areg and 6 of its target genes: cyclin A2, centromere protein F, marker of proliferation Ki-67, protein regulator of cytokinesis 1, ribonucleotide reductase M2, and topoisomerase II alpha. We confirmed high mRNA expression of Areg and its 6 target genes in both the urothelium of rats treated for 4 weeks with DMA and in DMA-induced tumors. RNA interference of human amphiregulin (AREG) expression in human urinary bladder cell lines T24 and UMUC3 decreased expression of AREG and its 6 target genes and decreased cell proliferation. These data suggest that Areg has an important role in DMA-induced rat bladder carcinogenesis.

Determination of Arsenic Species in Edible Insects by LC-ICP-MS.

BACKGROUND: Edible insects may contain arsenic. Analysis of arsenic species is necessary in order to accurately assess arsenic exposure. OBJECTIVE: An analytical method was validated and used to determine and quantitate arsenic species in edible insects. METHODS: Arsenic species were extracted from edible insects by heating at 100°C in 0.3 mol/L nitric acid. The concentration of arsenic species was then determined by LC-inductively coupled plasma-mass spectrometry (LC-ICP-MS) using an octadecylsilane (ODS) column with a mobile phase containing an ion-pair reagent. RESULTS: The LOD (0.007-0.012 mg/kg), LOQ (0.021-0.038 mg/kg), repeatability (1.2-3.2%), intermediate precision (2.8-4.5%), and trueness (recoveries 97-102% based on spiked samples) of the proposed method were satisfactory for inorganic arsenic, dimethylarsinic acid (DMA), and arsenobetaine (AB) in edible insects. Total arsenic was detected in all samples obtained in Japan (Asian forest scorpion, diving beetles, giant water bug, grasshoppers, June beetles, mole crickets, male rhino beetle, female rhino beetle, sago worms, and silkworm pupae) and consisted of mostly inorganic arsenic. Beetles in particular showed relatively high levels. CONCLUSION: Arsenic content varies among edible insect species. Feed control is important, as arsenic concentrations in edible insects may be feed dependent. HIGHLIGHTS: Arsenic species in edible insects were analyzed by LC-ICP-MS using an ODS column with a mobile phase containing an ion-pair reagent. Inorganic arsenic was detected in most samples, with concentrations ranging from <0.04 to 29.3 mg/kg.

Influence of genetic polymorphisms on arsenic methylation efficiency during pregnancy: Evidence from a Spanish birth cohort.

BACKGROUND: Inorganic arsenic (iAs) is a widespread toxic metalloid. It is well-known that iAs metabolism and its toxicity are mediated by polymorphisms in AS3MT and other genes. However, studies during pregnancy are scarce. We aimed to examine the role of genetic polymorphisms in AS3MT, GSTO2, N6AMT1, MTHFR, MTR, FTCD, CBS, and FOLH1 in iAs methylation efficiency during pregnancy. METHODS: The study included 541 pregnant participants from the INMA (Environment and Childhood) Spanish cohort. Using high-performance liquid chromatography coupled to inductively coupled plasma-tandem mass, we measured arsenic (iAs and the metabolites monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)) in urine samples collected during the first trimester. iAs methylation efficiency was determined based on relative concentrations of the As metabolites in urine (%MMA, %DMA, and %iAs). Thirty-two single nucleotide polymorphisms (SNPs) in nine genes were determined in maternal DNA; AS3MT haplotypes were inferred. We assessed the association between genotypes/haplotypes and maternal As methylation efficiency using multivariate linear regression models. RESULTS: The median %MMA and %DMA were 5.3 %, and 89 %, respectively. Ancestral alleles of AS3MT SNPs (rs3740393, rs3740390, rs11191453, and rs11191454) were significantly associated with higher %MMA, %iAs, and lower %DMA. Pregnant participants with zero copies of the GGCTTCAC AS3MT haplotype presented a higher %MMA. Statistically significant associations were also found for the FOLH1 SNP rs202676 (ß 0.89 95%CI: 0.24, 1.55 for carriers of the G allele vs. the A allele). CONCLUSIONS: Our study shows that ancestral alleles in AS3MT polymorphisms were associated with lower As methylation efficiency in early pregnancy and suggests that FOLH1 also plays a role in As methylation efficiency. These results support the hypothesis that As metabolism is multigenic, being a key element for identifying susceptible populations.

Multigenerational effects of co-exposure to dimethylarsinic acid and polystyrene microplastics on the nematode Caenorhabditis elegans.

In the current study, we assessed the impact of DMA (dimethylarsinic acid) and MPs (microplastics) interactions in C. elegans over the course of five generations. We found that the redox state of the organisms changed over generations as a result of exposure to both pollutants. From the third generation onward, exposure to MPs reduced GST activity, indicating reduced detoxifying abilities of these organisms. Additionally, dimethylarsinic exposure decreased the growth of organisms in the second, fourth, and fifth generations. In comparison to isolated pollutants, the cumulative effects of co-exposure to DMA and MPs seem to have been more harmful to the organisms, as demonstrated by correlation analysis. These findings demonstrate that DMA, despite being considered less hazardous than its inorganic equivalents, can still have toxic effects on species at low concentrations and the presence of MPs, can worsen these effects.

Prenatal arsenic exposure, arsenic metabolism and neurocognitive development of 2-year-old children in low-arsenic areas.

BACKGROUND: There is limited evidence on the effects of arsenic species and metabolic capacity on child neurodevelopment, particularly at low levels. Further, little is known about the critical window of exposure. OBJECTIVE: To estimate the associations of arsenic exposure and arsenic metabolism in different pregnancy periods with neurodevelopment of two-year-old children. METHODS: Concentrations of arsenobetaine (AsB), arsenite, arsenate, monomethyl arsenic acid (MMA), and dimethyl arsenic acid (DMA) in urine samples collected in three trimesters from 1006 mothers were measured using HPLC - ICPMS. Inorganic arsenic (iAs) was calculated as the sum of arsenite and arsenate. Total arsenic (tAs) was calculated as the sum of iAs, MMA and DMA. Child neurodevelopment was assessed with the Bayley Scales of Infant Development. RESULTS: The geometric mean (GM) of SG-adjusted tAs in the first, second, third trimester was 16.37, 12.94, 13.04 µg/L, respectively. The mental development index (MDI) score was inversely associated with iAs and tAs. Compared to the 1st quartile, the MDI score decreased 0.43 (95%CI: -4.22, 3.36) for the 2nd, 6.50 (95%CI: -11.73, -1.27) for the 3rd, 5.42 (95%CI: -10.74, -0.10) for the 4th quartiles of iAs, and decreased 4.03 (95%CI: -7.90, -0.15) in the 4th quartile of tAs. In trimester-specific models, negative associations of DMA [-1.94 (95%CI: -3.18, -0.71)] and tAs [-1.61 (95%CI: -3.02, -0.20)] with the psychomotor development index (PDI) were only observed in 1st trimester. CONCLUSIONS: Our study found inverse associations between prenatal arsenic exposure, especially in early pregnancy, and neurodevelopment of children at two years old, even at low exposure levels.

Decreasing arsenic in rice: Interactions of soil sulfate amendment and water management.

Accumulation of inorganic arsenic (iAs) and dimethylarsenate (DMA) in rice threatens human health and rice yield, respectively. We studied the yet unclear interactions of soil sulfate amendment and water management for decreasing As accumulation in rice grain in a pot experiment. We show that soil sulfate amendment (+200 mg S/kg soil) decreased grain iAs by 44% without clearly increasing grain DMA under intermittent flooding from booting stage to maturation. Under continuous flooding during this period, sulfate amendment decreased grain iAs only by 25% but increased grain DMA by 68%. The mechanisms of sulfate amendment effects on grain iAs were not explained by porewater composition or in-planta As sequestration but were allocated to the rhizosphere. Grain iAs closely correlated with As in the root iron-plaque (r = 0.92) which was effectively decreased by sulfate amendment and may have acted as an iAs source for rice uptake. Although both sulfate amendment and intermittent flooding substantially increased porewater DMA concentrations, it was the continuous flooding, irrespective of sulfate amendment, that resulted in rice straighthead disease with 47-55% less yield and 258-320% more DMA in grains than intermittent flooding. This study suggests that combining soil sulfate amendment and intermittent flooding can help to secure the quantity and quality of rice produced in As-affected areas. Our results also imply the key role of rhizosphere processes in controlling both iAs and DMA accumulation in rice which should be elucidated in the future.

Associations of arsenic exposure with liver injury in US adults: NHANES 2003-2018.

Arsenic is a natural element with complex toxicity. Long-term exposure to arsenic can cause a variety of health damage. In recent years, there are some studies on arsenic exposure and liver injury. But few of them tried to measure the quantitative relationship between arsenic exposure and indicators of liver injury in adult. Therefore, this study aimed to elucidate the relationship between them. This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) in 2003-2018. Arsenic exposure was assessed using total urinary arsenic and dimethylarsenate acid (DMA). We selected alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total protein (TP), ALT/AST, total bilirubin (TBIL), and albumin (ALB) as markers of liver injury. Multiple linear regression was used to explore the relationship between urinary arsenic concentrations and these markers of liver function injury. In addition, six covariables (age, sex, smoker, alcohol user, BMI, diabetes) were further analyzed in subgroups. A total of 13,420 adults were included in the analysis. The multivariate linear regression analyses showed that urinary DMA was positively correlated with ALT (ß 0.135, 95%CI 0.090, 0.180, p < 0.001), AST (ß 0.053, 95%CI 0.014, 0.092, p < 0.01), ALT/AST (ß 0.052, 95%CI 0.030, 0.074, p < 0.001), TBIL (ß 0.061, 95%CI 0.034, 0.089, p < 0.001), and GGT (ß 0.178, 95%CI 0.110, 0.246, p < 0.001). Similar results were observed for total urinary arsenic, suggesting a positive association with AST (ß 0.048, 95%CI 0.016, 0.081, p < 0.01), ALT (ß 0.090, 95%CI 0.049, 0.132, p < 0.001), and TBIL (ß 0.062, 95%CI 0.037, 0.088, p < 0.001). In subgroup analysis, sex and smoker showed significant differences between subgroups. Our results demonstrate a positive association between urinary arsenic exposure and liver injury in adults. Sex and smokers may be related to arsenic pathogenicity.

Arsenic metabolism, N6AMT1 and AS3MT single nucleotide polymorphisms, and their interaction on gestational diabetes mellitus in Chinese pregnant women.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in N6AMT1 and AS3MT are associated with arsenic (As) metabolism, and efficient As methylation capacity has been associated with diabetes. However, little is known about the gene-As interaction on gestational diabetes mellitus (GDM). OBJECTIVE: This study aimed to explore the individual and combined effects of N6AMT1 and AS3MT SNPs with As metabolism on GDM. METHODS: A cross-sectional study was performed among 385 Chinese pregnant women (86 GDM and 299 Non-GDM). Four SNPs in N6AMT1 (rs1997605 and rs1003671) and AS3MT (rs1046778 and rs11191453) were genotyped. Urinary inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were determined, and the percentages of As species (iAs%, MMA%, and DMA%) were calculated to assess the efficiency of As metabolism. RESULTS: Pregnant women with N6AMT1 rs1997605 AA genotype had lower iAs% (B: 2.11; 95% CI: 4.08, -0.13) and MMA% (B: 0.21; 95% CI: 0.39, -0.04) than pregnant women with GG genotype. The AS3MT rs1046778 and rs11191453 C alleles were negatively associated with iAs% and MMA% but positively associated with DMA%. Higher urinary MMA% was significantly associated with a lower risk of GDM (OR: 0.54; 95% CI: 0.30, 0.97). The A allele in N6AMT1 rs1997605 (OR: 0.46; 95% CI: 0.26, 0.79) was associated with a decreased risk of GDM. The additive interactions between N6AMT1 rs1997605 GG genotypes and lower iAs% (AP: 0.50; 95% CI: 0.01, 0.99) or higher DMA% (AP: 0.52; 95% CI: 0.04, 0.99) were statistically significant. Similar additive interactions were also found between N6AMT1 rs1003671 GG genotypes and lower iAs% or higher DMA%. CONCLUSIONS: Genetic variants in N6AMT1 and efficient As metabolism (indicated by lower iAs% and higher DMA%) can interact to influence GDM occurrence synergistically in Chinese pregnant women.

How do different arsenic species affect the joint toxicity of perfluorooctanoic acid and arsenic to earthworm Eisenia fetida: A multi-biomarker approach.

Perfluorooctanoic acid (PFOA) and arsenic are widely distributed pollutants and can coexist in the environment. However, no study has been reported about the effects of different arsenic species on the joint toxicity of arsenic and PFOA to soil invertebrates. In this study, four arsenic species were selected, including arsenite (As(III)), arsenate (As(V)), monomethylarsonate (MMA), and dimethylarsinate (DMA). Earthworms Eisenia fetida were exposed to soils spiked with sublethal concentrations of PFOA, different arsenic species, and their binary mixtures for 56 days. The bioaccumulation and biotransformation of pollutants, as well as eight biomarkers in organisms, were assayed. The results indicated that the coexistence of PFOA and different arsenic species in soils could enhance the bioavailability of arsenic species while reducing the bioavailability of PFOA, and inhibit the arsenic biotransformation process in earthworms. Responses of most biomarkers in joint treatments of PFOA and As(III)/As(V) showed more significant variations compared with those in single treatments, indicating higher toxicity to the earthworms. The Integrated Biomarker Response (IBR) index was used to integrate the multi-biomarker responses, and the results also exhibited enhanced toxic effects in combined treatments of inorganic arsenic and PFOA. In comparison, both the biomarker variations and IBR values were lower in joint treatments of PFOA and MMA/DMA. Then the toxic interactions in the binary mixture systems were characterized by using a combined method of IBR and Effect Addition Index. The results revealed that the toxic interactions of the PFOA/arsenic mixture in earthworms depended on the different species of arsenic. The combined exposure of PFOA with inorganic arsenic led to a synergistic interaction, while that with organic arsenic resulted in an antagonistic response. Overall, this study provides new insights into the assessment of the joint toxicity of perfluoroalkyl substances and arsenic in soil ecosystems.

Arsenic exposure and prevalence of human papillomavirus in the US male population.

Arsenic is a known carcinogen and is naturally available in earth's crust. Inorganic arsenic is an environmental pollutant with immunosuppressive properties. Human papillomavirus (HPV) is considered one of the most common sexually transmitted diseases in the United States. HPV is linked to several types of cancers in males, including oral, anal, and penile cancer. However, limited information is available on the effect of arsenic on HPV in males. The purpose of this study was to examine the association of urinary arsenic species (speciated and total) and the prevalence of HPV infection in the male population. HPV prevalence in males was analyzed using the 2013-2014 and 2015-2016 National Health and Nutrition Examination Survey (NHANES) dataset. Logistic regression analysis was used to examine associations of seven types of urinary arsenic species (arsenous acid, arsenic acid, arsenobetaine, arsenocholine, dimethylarsinic acid (DMA), monomethylarsonic acid (MMA), total arsenic acid) with HPV risk for male participants aged 18-59 years (N = 1516). Demographic characteristics were included in the logistic regression model for each arsenic variable. All statistical analyses were conducted by using the software R (version 4.2.0). Increasing DMA was positively associated with the prevalence of low-risk HPV (odds ratio (OR): 1.075, 95% confidence interval (CI): 1.025, 1.128) in addition to the sum of total toxic arsenic species (TUA1) including arsenous acid, arsenic acid, DMA, and MMA (OR: 1.068, 95% CI: 1.022, 1.116). High-risk HPV strains were found to be positively associated with arsenic acid (OR: 1.806, 95% CI: 1.134, 2.876) and total arsenic minus the sum of the two organic arsenic species arsenobetaine and arsenocholine (TUA2) at quartile 3 (Q3) level (OR: 1.523, 95% CI: 1.102, 2.103). The logistic regression models also showed that race and marital status were significant factors related to high-risk HPV. Our study reported that DMA and TUA1 are associated with low-risk HPV and arsenic acid is associated with high-risk HPV infections in males. Future research is required to confirm or refute this finding.