Arsenic Methylation Research Articles

Assessment of the effects of organic vs. inorganic arsenic and mercury in Caenorhabditis elegans

Exposures to mercury and arsenic are known to pose significant threats to human health. Effects specific to organic vs. inorganic forms of these toxic elements are less understood however, especially for organic dimethylarsinic acid (DMA), which has recently been detected in pups of rodent dams orally exposed to inorganic sodium (meta)arsenite (NaAsO2). Caenorhabditis elegans is a small animal alternative toxicity model. To fill data gaps on the effects of DMA relative to NaAsO2, C. elegans were exposed to these two compounds alongside more thoroughly researched inorganic mercury chloride (HgCl2) and organic methylmercury chloride (meHgCl). For timing of developmental milestone acquisition in C. elegans, meHgCl was 2 to 4-fold more toxic than HgCl2, and NaAsO2 was 20-fold more toxic than DMA, ranking the four compounds meHgCl > HgCl2 > NaAsO2 ≫ DMA for developmental toxicity. Methylmercury induced significant decreases in population locomotor activity levels in developing C. elegans. DMA was also associated with developmental hypoactivity, but at >100-fold higher concentrations than meHgCl. Transcriptional alterations in native genes were observed in wild type C. elegans adults exposed to concentrations equitoxic for developmental delay in juveniles. Both forms of arsenic induced genes involved in immune defense and oxidative stress response, while the two mercury species induced proportionally more genes involved in transcriptional regulation. A transgenic bioreporter for activation of conserved proteosome specific unfolded protein response was strongly activated by NaAsO2, but not DMA at tested concentrations. HgCl2 and meHgCl had opposite effects on a bioreporter for unfolded protein response in the endoplasmic reticulum. Presented experiments indicating low toxicity for DMA in C. elegans are consistent with human epidemiologic data correlating higher arsenic methylation capacity with resistance to arsenic toxicity. This work contributes to the understanding of the accuracy and fit-for-use categories for C. elegans toxicity screening and its usefulness to prioritize compounds of concern for further testing.

Variation in Arsenic metabolism in schistosomiasis associated bladder pathology in a rural community, Eggua, Ogun State, Nigeria

Exposure to toxic inorganic Arsenic (iAs) in areas endemic for urogenital schistosomiasis may confer increased risk for bladder cancer. The severity of the adverse effects of iAs however depends on its metabolism, which is highly variable among individuals. Genetic polymorphism in Arsenic (+3) Methyl Transferase enzyme, accounts significantly for these variations. To investigate the relationship of AS3MT gene polymorphisms and Arsenic metabolism to schistosomiasis and/or associated bladder pathology, 119 individualsfrom Eggua in southwest Nigeria were recruited for this study. Screening for schistosomiasis and bladder pathology was done by microscopy and ultrasonography respectively. Wagtech Digital Arsenator was used to assess total urinary arsenic concentrations and thus determine the level of arsenic exposure. The single nucleotide polymorphism AS3MT/Met287Thr T>C (rs11191439) was genotyped using Alelle-Specific PCR. Of the participants who tested positive for schistosomiasis, 33.3% exhibited bladder pathology. Total urinary arsenic concentration in 80% of the participants was above the WHO limit of 0.05mg/L. The Met287Thr allelic distribution conformed to the Hardy-Weinberg equilibrium (X2= 0.161, P> 0.05). Observed allelic frequencies were 0.96 and 0.04 for wild-type T and mutant C alleles respectively. There was no significant relationship between AS3MT SNP, arsenic concentrations and schistosomiasis associated bladder pathology. In conclusion, the community is highly exposed to arsenic, although with a possible genetic advantage of increased AS3MT catalytic activity. However, we see the need for urgent intervention as inter-individual differences in arsenic metabolism may influence the bladder pathology status of individuals in the community. And although urogenital schistosomiasis is waning in Eggua, it is not known what synergy the infection and high arsenic exposure may wield on bladder pathology.

Arsenic Biotransformation: It is a complex process

Arsenic Biotransformation: It is a complex process

Polymorphisms of the AS3MT gene are associated with arsenic methylation capacity and damage to the P21 gene in arsenic trioxide plant workers.

Epidemiological evidence suggests that the metabolic profiles of each individual exposed to arsenic (As) are related to the risk of cancer, coronary heart disease, and diabetes. The arsenite methyltransferase (AS3MT) gene plays a key role in As metabolism. Several single nucleotide polymorphisms in the AS3MT gene may affect both enzyme activity and gene transcription. AS3MT polymorphisms are associated with the proportions of monomethylarsenic acid (MMA) and dimethylarsenic acid (DMA) in urine as well as the incidence of cancer. P21 protein is a cyclin-dependent kinase inhibitor. Mutations of the P21 gene have been found in cancer patients. In our study, we investigate whether polymorphisms of the AS3MT gene alter As methylation capacity and adversely affect the P21 gene in arsenic trioxide plant workers. The DNA damage was examined by the quantitative polymerase chain reaction. Restriction fragment length polymorphism was used to analyze the genotype of the AS3MT gene. The results showed that DNA damage in P21 gene fragments was greater in those individuals exposed to high levels of As. There was a strong positive correlation between the DNA damage to P21 gene fragments and the percentage of MMA in urine. However, DNA damage in P21 gene fragments was negatively associated with the percentage of DMA in urine (%uDMA), primary methylation index (PMI), and secondary methylation index. We found that subjects with the rs7085104 GG or GA allele were associated with higher %uDMA and PMI and less DNA damage. The subjects with the rs11191454 GG+GA or GA allele were also associated with higher %uDMA and PMI and less DNA damage. Our results suggest that rs1191454 and rs7085104 in the AS3MT gene affect the As-induced DNA damage by altering individual metabolic efficiency.

Nickel (Ni) may have influenced on the MMA(V) reductase and DMA(V) reductase activities for inorg-As biotransformation process in humans

Trace elements (As, Se, Zn, Co, Cu, Pb, Cd, Ni, Mn, and Hg) were analyzed in blood of arsenic exposed people in Mexico by using ICP-MS to know the influence of trace elements on the MMA(V) and DMA(V) reductase activities for inorganic arsenic biotransformation process. The correlations between MMA(V) reductase and DMA(V) reductase activities in blood of both females and males were very weak (F, r= +0.06 and M, r= -0.03, respectively). The activities of MMA(V) and DMA(V) reductase were also not depended on ages of those population (r= -0.05 and r= -0.11, respectively). In this study, there were no significant differences of the MMA(V) reductase and DMA(V) reductase activities in bloods of females and males. Nickel concentrations in blood were positively and negatively correlated with MMA(V) and DMA(V) reductase activities in blood of both females and males, respectively. These correlations were statistically significant for females. In conclusion of this study suggest that Ni may have influenced for biotransformation process of inorganic arsenic (inorg-As) in humans and it could enhance arsenic methylation, decrease urinary MMA, and increase urinary DMA. Abbreviation: SAM, S-adenosyl-L-methionine; SAHC, S-adenosyl-L-homocysteine

Cover crops and residual herbicides reduce selection pressure for Palmer amaranth resistance to dicamba‐applied postemergence in cotton

AbstractThe most widely planted cotton (Gossypium hirsutum L.) and soybean [Glycine max (L.) Merr.] varieties in the United States are resistant to the herbicide dicamba. Measures to reduce selection pressure for dicamba‐resistant weeds is paramount. Four studies evaluated strategies to reduce selection pressure for Palmer amaranth (Amaranthus palmeri S. Watson) resistance to dicamba applied postemergence (POST) in cotton. A split‐plot arrangement consisted of conventional tillage or cereal rye (Secale cereale L.) cover crop as the whole plot. The subplot included four herbicide systems: no herbicide, 3 POSTs, fomesafen plus diuron applied pre‐emergence (PRE) followed by (fb) 3 POSTs, and PRE fb 2 POSTs fb diuron plus monosodium methyl arsenate applied lay‐by post‐directed (LPD). The POST herbicide applications were glyphosate plus dicamba. The cover crop reduced Palmer amaranth density 75, 70, and 54% at the time of POST 1, POST 2, and POST 3 application, respectively. Pre‐emergence herbicides fb POST applications reduced Palmer amaranth densities 99, 99, and 96% at the aforementioned application timings, respectively. Cover crop plus PRE herbicides provided similar reductions. Cumulative for the season, Palmer amaranth exposure to dicamba was reduced 65% by the cover crop, 98% by both PRE herbicides and cover crop plus PRE herbicides compared to 3 POST applications. An LPD application reduced Palmer amaranth exposure to dicamba by 38,319 plants ha–1 compared to a third POST. Cotton stand was higher in conventional systems when soil temperatures were 30–37 °C during emergence; however, stand in the cover crop was greater when soil temperatures were 40–43 °C. Yields were reduced 14% in a total POST herbicide program, and were improved 14% in a cover crop. A cereal rye cover crop and residual PRE herbicides had the biggest impact on reducing selection pressure for Palmer amaranth resistance to dicamba while also improving yield.

Food Chain Arsenic: Additional body burden on health of arsenic

Introduction
 
 
 Arsenic: The king of poisons, the poisons of kings, and the bane of investigators1. The IARC2 has classified arsenic as a group 1 human carcinogen. Chronic exposure to inorganic arsenic can cause cancerous2-5 and non-cancerous health hazards6,7 in humans. Arsenic can get entry into the human body via drinking water, eating food, inhaling dust, and/or ingesting soil.
 
 In arsenic affected areas of West Bengal-India and Bangladesh huge quantity of arsenic is falling on agricultural land. A study in West Bengal-India reported that in a 201 km2 area of the Deganga block in the arsenic-affected district of North 24-Parganas, 6.4 tons of arsenic is falling on agricultural land in one year from 3200 contaminated tube wells for agricultural irrigation8. They expect tons of arsenic is coming with underground water in the arsenic affected areas of West Bengal-India and Bangladesh and falling on irrigated land. Thus, it is expected arsenic is entering the food chain.
 
 
 
 
 
 Figure. Using tube well water for agricultural irrigation.
 
 Rice and vegetable are the staple food for poor villagers of West Bengal, India and Bangladesh. This is true for the villagers in Kolsur gram-panchayet (G.P.) in Deganga block of North 24-Parganas district, West Bengal-India, where a group of researchers studied for arsenic in soil, rice, and vegetables from fields cultivated with arsenic contaminated water. From the results of total arsenic (drinking water + rice + vegetables + Pantavat + water added for food preparation) body burden to North Kolsur villagers [1185.0 µg for per adult per day and 653.2 µg for per child (around 10 years) per day], as the amount of arsenic coming from rice, vegetables, and water added for Pantavat and food preparation is 485 µg i.e., 41% of total for adult and 253.2 µg i.e., 38.8% for child and from rice and vegetable 285 µg i.e., 24% of total for adult and 153.2 µg i.e., 23.4% for child9-11. Their findings show most of the arsenic coming from food is inorganic in nature10. They reported that 95% and 5% of the arsenic are inorganic arsenic and methylated arsenic in rice, and 96% and 4% are inorganic arsenic and methylated arsenic in vegetables, respectively10.
 
 According to WHO12 1.0 µg of inorganic arsenic per day may give rise to skin effects within a few years.
 It has been estimated that based upon the current U.S. Environmental Protection Agency (EPA) standard of 50 µg/L, the lifetime risk of dying from cancer of the liver, lung, kidney, or bladder, from drinking 1 liter per day of water could be as high as 13 per 1000 persons13. Using the same methods, the risk estimate for 500 µgL of arsenic in drinking water would be 13 per 100 persons14. In its latest document on arsenic in drinking water, the U.S. National Research Council (NRC) concluded that exposure to 50 µg/L could easily result in a combined cancer risk15 of 1 in 100. Comparing to the WHO, EPA, and NRC document with arsenic burden to Kolsur villagers from water and food it appears that Kolsur villagers’ risk of suffering from arsenical skin effect and cancer is there. Compared to worldwide arsenic consumption from food, it appears Kolsur villagers are also consuming high amount of inorganic arsenic from food and vegetables. Kolsur village is an example of many such villages in West Bengal-India and Bangladesh.
 Furthermore, products from arsenic irrigated water- soil system rich in arsenic are also coming to common marketplace far away from contaminated areas and even people who are not drinking arsenic contaminated water may get arsenic from food products produced from contaminated fields. In West Bengal-India and Bangladesh rice, vegetables, and other products are coming to cities (including Kolkata in West Bengal-India and Dhaka in Bangladesh) from villages and possibility that city people consuming arsenic contaminated products from contaminated areas cannot be ruled out.

Provision of folic acid for reducing arsenic toxicity in arsenic-exposed children and adults.

Provision of folic acid for reducing arsenic toxicity in arsenic-exposed children and adults.

Prenatal arsenic exposure, arsenic methylation efficiency, and neuropsychological development among preschool children in a Spanish birth cohort

BackgroundPrenatal arsenic (As) exposure could negatively affect child neuropsychological development, but the current evidence is inconclusive. ObjectivesTo explore the relationship between prenatal urinary total As (TAs) concentrations, the As species and the methylation efficiency, and child neuropsychological development in a Spanish birth cohort. We also studied the effect modification produced by sex and several nutrients and elements. Materials and methodsStudy subjects were 807 mother–child pairs participating in the INMA (Childhood and Environment) Project. Urinary TAs and its metabolites, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), inorganic As (iAs) and arsenobetaine were measured in the first trimester of pregnancy. Methylation efficiency was determined through the percentages of the metabolites and using principal component analysis. Children's neuropsychological development was assessed at the age of 4–5 years using the McCarthy Scales of Children's Abilities (MSCA). Multivariable linear regression models were built to assess the association between TAs, the As species and the maternal methylation efficiency, and the neuropsychological scores. We explored effect modification by sex, iron status, maternal nutrients status (serum manganese and selenium, and urinary zinc), and maternal vitamins intake (folate, and vitamins B12 and B6). ResultsThe geometric mean (95%CI) of ∑As (sum of DMA, MMA and iAs) was 7.78 (7.41, 8.17) μg/g creatinine. MMA concentrations were inversely associated with the scores for the general, verbal, quantitative, memory, executive function and working memory scales (i.e. β [CI95%] = −1.37 [-2.33, −0.41] for the general scale). An inverse association between %MMA and the memory scores was found. Children whose mothers had lower manganese, zinc and ferritin concentrations obtained lower scores on several MSCA scales with decreasing As methylation efficiency. DiscussionAn inverse association was observed between MMA concentrations and children's neuropsychological development. Maternal levels of manganese, zinc and ferritin affected the association between As methylation efficiency and MSCA scores.

Effect of rainwater oxidants on As volatilization in the soil-rice system

Rainwater contains multiple oxidants, such as hydrogen peroxide (H2O2) and perchlorate (ClO4−). The aim of the study was to investigate the rainwater of trace H2O2 and ClO4− affected on the arsenic (As) methylation and volatilization in the rice paddy of As contamination (arsenite (As(III)) and roxarsone (Rox)). Heavy rainfall monitoring and simulation experiments were applied in this study. The result showed that the H2O2 and ClO4− of heavy rainfall in 2017 was 5.3–51.6 μmol/L and ND - 6.1 μg/L respectively. Because of the differences in chemical properties, H2O2 and ClO4− affected As methylation and volatilization of paddy soil in different ways. H2O2 performed a temporary effect on As volatilization, which was mainly in the 1st-hour and restored to the controls condition finally. However, ClO4− showed a persistent inhibition on As volatilization which decreased 32 %–69 % in the whole test. In general, the trend of volatilization was following the order: CK ≈ H2O2 > ClO4−. The oxidants (H2O2 and ClO4−) also could decrease As(III) in 37 %–44 % and increased As(V) in 24 %–272 %. In addition, planting rice in As contamination soil could enhance As volatilization by 36 %–334 %. These suggested that planting wetland plants on As-contaminated soil probably become a potential way to increase As volatilization.

Enhanced water decontamination from methylated arsenic by utilizing ultra-small hydrated zirconium oxides encapsulated inside gel-type anion exchanger

Methylated arsenic species, including monomethyl arsenate (MMA) and dimethyl arsenate (DMA), are frequently detected in natural waters due to the biochemical methylation of arsenic and various human activities. The presence of MMA/DMA may cause excess total arsenic (>10 μg/L) in drinking water, yet the efficient removal of methylated arsenic still remains challenging. Herein, we reported the utilization of a recently developed nanocomposite HZO@N201 for selective removal of MMA and DMA from water. HZO@N201 contains the gel-type anion exchanger N201, i.e., quaternary ammoniated poly(styrene-co-divinylbenzene) beads, as the host, and the embedded sub-5 nm hydrated zirconium oxide (HZO) for specific adsorption. In comparison with the commercially available nanocomposite HZO@D201, which was prepared through in-situ growth of HZO inside the macroporous anion exchanger D201, the adsorption capacities of HZO@N201 toward MMA and DMA ascended by ∼ 1.9 and ∼ 2.2 times, respectively, mainly benefitting from the sub-5 nm nature of HZO@N201. The competing anions including sulfate, chloride and bicarbonate exerted negligible impact on the removal efficiency toward MMA/DMA, due to inner-sphere complex formation between HZO NPs and MMA/DMA, as verified by SEM-EDS and XPS Zr 3d analysis. The exhausted HZO@N201 was fully regenerated by alkaline treatment for cyclic utilization without obvious efficiency loss. In fixed-bed experiments, HZO@N201 column was able to successively produce ∼ 4000 and ∼ 160 bed volume (BV) clean water from the feeding solutions containing MMA and DMA, while the values for HZO@D201 column were merely ∼ 1600 BV and ∼ 70 BV, respectively.

Arsenic Secondary Methylation Capacity Is Inversely Associated with Arsenic Exposure-Related Muscle Mass Reduction.

Skeletal muscle mass reduction has been implicated in insulin resistance (IR) that promotes cardiometabolic diseases. We have previously reported that arsenic exposure increases IR concomitantly with the reduction of skeletal muscle mass among individuals exposed to arsenic. The arsenic methylation capacity is linked to the susceptibility to some arsenic exposure-related diseases. However, it remains unknown whether the arsenic methylation capacity affects the arsenic-induced reduction of muscle mass and elevation of IR. Therefore, this study examined the associations between the arsenic methylation status and skeletal muscle mass measures with regard to IR by recruiting 437 participants from low- and high-arsenic exposure areas in Bangladesh. The subjects’ skeletal muscle mass was estimated by their lean body mass (LBM) and serum creatinine levels. Subjects’ drinking water arsenic concentrations were positively associated with total urinary arsenic concentrations and the percentages of MMA, as well as inversely associated with the percentages of DMA and the secondary methylation index (SMI). Subjects’ LBM and serum creatinine levels were positively associated with the percentage of DMA and SMI, as well as inversely associated with the percentage of MMA. HOMA-IR showed an inverse association with SMI, with a confounding effect of sex. Our results suggest that reduced secondary methylation capacity is involved in the arsenic-induced skeletal muscle loss that may be implicated in arsenic-induced IR and cardiometabolic diseases.

Arsenic Methylation and Body Composition among Pregnant Women in Rural Northern Bangladesh: The Pregnancy, Arsenic, and Immune Response (PAIR) Study

BACKGROUND AND AIM: Arsenic methylation—the conversion of inorganic arsenic (iAs) to less toxic monomethyl (MMA) and dimethyl (DMA) species—could modify the developmental and reproductive toxicity of this metalloid. However, variability in arsenic methylation among pregnant women remains poorly understood. Arsenic methylation efficiency—the percentage of urinary arsenic methylated to DMA (DMA%)—is positively associated with body mass index (BMI) in pregnant women, but BMI is an ambiguous measure of body composition. We estimated arsenic methylation by body fat percentage as well as BMI in pregnant women in Bangladesh. METHODS: We collected spot urine samples from pregnant women (n=784) in gestational weeks 11-17 and measured weight, height, and subscapular and triceps skinfolds. Urinary arsenic was speciated by HPLC-ICPMS. Arsenic metabolism was assessed by urinary iAs, MMA, and DMA, which were specific gravity-corrected, divided by their sum (∑As), and multiplied by 100 (iAs%, MMA%, and DMA%). Body fat (%) was estimated using Siri’s equation with body density estimated from skinfolds. We fit linear models of iAs%, MMA%, or DMA% by body fat or BMI (kg/m2), adjusting for ln ∑As (µg/L), age (years), and gestational week. RESULTS:In complete cases (n=771), median (IQR) iAs%, MMA%, DMA%, and ∑As were 12.1% (5.8%), 6.6% (3.0%), 81.0% (7.5%), and 33.3 µg/L (37.2 µg/L). Median (IQR) body fat and BMI were 28.4% (9.1%) and 21 kg/m2 (4.4 kg/m2), and were highly correlated (Spearman’s rho=0.83). Before adjustment, body fat was negatively associated with iAs% (beta per IQR-unit increase: -1.00, 95%CI: -1.50,-0.50) and MMA% (-0.65, 95%CI: -0.90,-0.39) and positively associated with DMA% (1.65, 95%CI: 1.00,2.30). BMI was negatively associated with iAs% (beta per IQR-unit increase: -0.85, 95%CI: -1.29,-0.41) and MMA% (-0.69, 95%CI: -0.91,-0.47) and positively associated with DMA% (1.54, 95%CI: 0.98,2.10). After adjustment, results were similar. CONCLUSIONS:Arsenic methylation efficiency was positively associated with body fat and BMI among pregnant women in Bangladesh. KEYWORDS: Biomarkers of exposure, Chemical exposures, Female, Heavy metals, Obesity and metabolic disorders, Pregnancy outcomes

The Effect of Manure Application on Arsenic Mobilization and Methylation in Different Paddy Soils.

Organic matter plays an important rolein controlling arsenic(As) release and transformation in soil, however, little is known about the effect of manure application on As behavior in soils with different As contents. In this study, waterlogged incubations using various As-contaminated paddy soils with manure amendment were conducted to investigate how manure application influence As mobilization and methylation in different paddy soils. The results indicated that manure application increased As release in paddy soils with high As (> 30mgkg-1) contents. Moreover, our findings also showed that manure application increased the relative abundance of arsM-harboring Euryacheota and Planctomycetes at the phylum level and arsM-harbouring Methanocellaceae, Anaerolinea and Bellinea at genus level, thereby promoting As methylation. These results provide important insights for the significant variation in As mobilization and methylation in paddy soils amended with manure. Moreover, our results suggest that serious consideration should be given to the manure application in As-contaminated paddy soil.

The relatively higher concentrations of trace elements to arsenic may have influenced on methylation process of inorg- As in humans

The relatively higher concentrations of trace elements to arsenic may have influenced on methylation process of inorg- As in humans

Arsenic exposure promotes the emergence of cardiovascular diseases

A large number of studies conducted in the past decade 2010-2020 refer to the impact of arsenic (As) exposure on cardiovascular risk factors. The arsenic effect on humans is complex and mainly depends on the varying individual susceptibilities, its numerous toxic expressions and the variation in arsenic metabolism between individuals. In this review we present relevant data from studies which document the association of arsenic exposure with various biomarkers, the effect of several genome polymorphisms on arsenic methylation and the underling molecular mechanisms influencing the cardiovascular pathology. The corresponding results provide strong evidence that high and moderate-high As intake induce oxidative stress, inflammation and vessel endothelial dysfunction that are associated with increased risk for cardiovascular diseases (CVDs) and in particular hypertension, myocardial infarction, carotid intima-media thickness and stroke, ventricular arrhythmias and peripheral arterial disease. In addition, As exposure during pregnancy implies risks for blood pressure abnormalities among infants and increased mortality rates from acute myocardial infarction during early adulthood. Low water As concentrations are associated with increased systolic, diastolic and pulse pressure, coronary heart disease and incident stroke. For very low As concentrations the relevant studies are few. They predict a risk for myocardial infarction, stroke and ischemic stroke and incident CVD,but they are not in agreement regarding the risk magnitude.

Roxarsone transformation and its impacts on soil enzyme activity in paddy soils: A new insight into water flooding effects

The aromatic arsenical roxarsone (ROX) has been used as feed additive for decades worldwide. The past or present application of animal manure containing ROX in paddy fields results in arsenic (As) accumulation in rice grain. However, the degradation and transformation mechanisms of ROX in paddy soil which determine As bioavailability and uptake by rice are still unclear. The current study investigated the variation of As speciation and soil enzyme activities in ROX-treated soils under flooded and non-flooded conditions for six months. Our results showed that 70.2% of ROX persisted in non-flooded paddy soils after 180 d while ROX degraded completely within 7 d in flooded soils. The rapid degradation of ROX under flooded conditions owed to the enhanced biotic transformation that was caused by the low Eh and the predominant presence of Clostridium spp. and Bacillus spp. ROX was not only transformed to As(III) and As(V) in non-flooded soils but also to 3-amino-4-hydroxyphenylarsonic acid and methyl arsenicals in flooded soils. The degradation products significantly inhibited soil enzyme activities for 7–30 d, but the inhibition effects disappeared after 90 d due to the sorption of transformed As products to amorphous Fe oxides. This study provides new insights into the flooding effect on ROX fate in paddy fields, which is important for the management of animal waste and risk control on polluted sites.

Effect of renal impairment on arsenic accumulation, methylation capacity, and safety in acute promyelocytic leukemia (APL) patients treated with arsenic trioxide

ABSTRACT Background: Arsenic trioxide (ATO) was successfully applied to treat acute promyelocytic leukemia (APL). Methods: Inorganic arsenic (iAs), monomethylarsonic acid (MMAV) and dimethyarsinic acid (DMAV) in plasma of 143 APL patients with different renal function were determined. Arsenic methylation capacity was evaluated by iAs%, MMAV%, DMAV%, primary methylation index (PMI, MMAV/iAs), and secondary methylated index (SMI, DMAV/MMAV). Arsenic accumulation with administration frequency were explored. Moreover, safety assessments were performed. Results: Compared with normal renal function, MMAV and DMAV concentrations increased 1.5–4 fold in moderate and severe renal impairment groups, iAs increased 1.3–1.7 fold. APL patients with renal impairment showed lower iAs%, but higher DMAV% and PMI in plasma than those with normal renal function (P < 0.05). MMAV, DMAV, and tAs apparently accumulated with administration frequency in moderate and severe renal dysfunction groups. The incidence of QTc interval prolongation and liver injury increased with the increasing severity of renal impairment. Conclusion: Renal dysfunction may increase exposure to arsenic and arsenic accumulation and affect methylation capacity, then the clinical safety in APL patients treated with ATO. Arsenic-level monitoring and dosing regimen adjustment should be considered in APL patients with moderate and severe renal dysfunction.

Selenium (Se) as well as mercury (Hg) may influence the methylation and toxicity of inorganic arsenic, but further research is needed with combination of Inorg-arsenic, Se, and Hg

Selenium (Se) as well as mercury (Hg) may influence the methylation and toxicity of inorganic arsenic, but further research is needed with combination of Inorg-arsenic, Se, and Hg

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