Interconnected soil iron and arsenic speciation effects on arsenic bioaccessibility and bioavailability: a scoping review.

Extensive research has examined arsenic (As) bioavailability in contaminated soils and is routinely assessed using in vitro bioaccessibility (IVBA) assays. Analysis of differences in bioaccessibility measurements across IVBA assays and phases is expected to provide valuable insights into geochemical mechanisms controlling soil As bioaccessibility and bioavailability. Soil iron (Fe) content and As speciation are expected to significantly influence IVBA gastric and intestinal phases due to fluctuations in precipitation-dissolution chemistry and sorption reactivity as pH and assay chemical complexity changes. The aim of this review was to examine these relationships by 1) conducting a meta-analysis (n = 47 soils) determining the influence of total Fe on As bioaccessibility measurements and 5 IVBA assays and 2) investigating the effect of As speciation on gastric/intestinal phase IVBA and in vitro-in vivo correlations. Our findings indicate that soil Fe content and As speciation heterogeneity are important in elucidating variability of bioaccessibility measurements across IVBA assays and gastrointestinal phases. Greater focus on coupled As speciation and Fe precipitation chemistry may (1) improve our understanding of soil geochemical factors and assay constituents that influence As in vitro-in vivo correlations and (2) resolve variability in the precision of oral relative bioavailability (RBA) estimated using IVBA assays for soils possessing heterogenous As speciation and Fe composition.

Bioavailability and health risk of toxic heavy metals (As, Hg, Pb and Cd) in urban soils: A Monte Carlo simulation approach.

Toxic heavy metals pollution in urban soil has become a major global issue due to its adverse effects on the environment and human health. In this paper, 26 soil samples were analyzed to assess the speciation, bioavailability and human health risk of Arsenic (As), Mercury (Hg), Lead (Pb) and Cadmium (Cd) in urban soils of a heavy industrial city in NE China by using a Monte Carlo simulation approach. The results showed that As, Hg, Pb and Cd concentrations in the soil all exceed the corresponding background value of study area. Mercury displays the highest value of geo-accumulation index (Igeo), followed by Cd, Pb and As. The pollution load index (PLI) value (>2) indicates a moderate pollution level in the study area. The chemical speciation of HMs mainly exists in residual fraction except Cd. The probabilistic health risk assessment demonstrated that the mean values of Total Carcinogenic Risk (TCR) and Hazard Index (HI) calculated with total concentration are at the unacceptable level, with a higher risk to children than adults. However, the mean values calculated with bioavailable fraction are all within the acceptable level. The mean value of TCR and HI obtained by bioavailable fraction is about 96% and 95% lower than that obtained by total concentration, respectively. Thus, this study suggested that the bioavailable fraction of HMs is a more reliable parameter for health risk assessment, while the total concentration of HMs can overestimate the true risk. The results of this study provide some insight into the speciation, bioavailability and health risks of toxic heavy metals in urban soils in those heavy industrial cities.

Augmented EPR effect post IRFA to enhance the therapeutic efficacy of arsenic loaded ZIF-8 nanoparticles on residual HCC progression.

BACKGROUND: Insufficient radiofrequency ablation (IRFA) can promote the local recurrence and distal metastasis of residual hepatocellular carcinoma (HCC), which makes clinical treatment extremely challenging. In this study, the malignant transition of residual tumors after IRFA was explored. Then, arsenic-loaded zeolitic imidazolate framework-8 nanoparticles (As@ZIF-8 NPs) were constructed, and their therapeutic effect on residual tumors was studied. RESULTS: Our data showed that IRFA can dramatically promote the proliferation, induce the metastasis, activate the epithelial-mesenchymal transition (EMT) and accelerate the angiogenesis of residual tumors. Interestingly, we found, for the first time, that extensive angiogenesis after IRFA can augment the enhanced permeability and retention (EPR) effect and enhance the enrichment of ZIF-8 nanocarriers in residual tumors. Encouraged by this unique finding, we successfully prepared As@ZIF-8 NPs with good biocompatibility and confirmed that they were more effective than free arsenic trioxide (ATO) in sublethal heat-induced cell proliferation suppression, apoptosis induction, cell migration and invasion inhibition, and EMT reversal in vitro. Furthermore, compared with free ATO, As@ZIF-8 NPs exhibited remarkably increased therapeutic effects by repressing residual tumor growth and metastasis in vivo. CONCLUSIONS: This work provides a new paradigm for the treatment of residual HCC after IRFA.

Evaluating the mouse model for estimation of arsenic bioavailability: Comparison of estimates of absolute bioavailability of inorganic arsenic in mouse, humans, and other species.

Accurate assessment of adverse health effects attributable to ingestion of inorganic arsenic (As) present in contaminated soils requires determination of the internal dose of metal provided by ingested soil. This calculation requires estimation of the oral bioavailability of soil-borne (As). Animal models to assess the bioavailability of soil (As) are frequently used as surrogates for determination of this variable in humans. A mouse assay has been widely applied to estimate the bioavailability of As in soils at sites impacted by mining, smelting, and pesticides. In the mouse assay, the relative bioavailability (RBA) of soil (As) is determined as the ratio of the fraction of the ingested arsenic dose excreted in urine after consumption of diets containing a test soil or the soluble reference compound, sodium arsenate. The aim of the current study was to compare (As) bioavailability measured in the mouse assay with reported estimates in humans. Here, a pharmacokinetic model based on excretion of arsenic in urine and feces was used to estimate the absolute bioavailability (ABA) of As in mice that received an oral dose of sodium arsenate. Based upon this analysis, in mice that consumed diet amended with sodium arsenate, the ABA was 85%. This estimate of arsenic ABA for the mouse is comparable to estimates in humans who consumed (As) in drinking water and diet, and to estimates of ABA in monkeys and swine exposed to sodium arsenate. The concordance of estimates for ABA in mice and humans provides further support for use of the mouse model in human health risk assessment. Sodium arsenate ABA also provides a basis for estimating soil arsenic ABA from RBA estimates obtained in the mouse model.

The simpler, the better: oral arsenic for acute promyelocytic leukemia.

Arsenic trioxide and all-trans retinoic acid have become the frontline treatments for patients with acute promyelocytic leukemia (APL). Despite the long wait for an oral arsenic drug, a commercially available agent, realgar-indigo naturalis formula (RIF), was not launched in China until 2009. Since then, over 5000 APL patients have been treated with oral RIF in China. Oral arsenic not only shows a clinical efficacy comparable to that of IV formulations but also displays a better safety profile, improved quality of life, and lower medical costs for patients. The promising results promote incorporating an outpatient postremission therapy model into clinical practice for both low-risk and high-risk APL patients in China. In this review, we discuss the evolution of oral arsenic RIF in the treatment of APL, with a special focus on how to address the related complications during induction therapy.

Exogenous melatonin regulates endogenous phytohormone homeostasis and thiol-mediated detoxification in two indica rice cultivars under arsenic stress.

KEY MESSAGE: Melatonin enhanced arsenic (As) tolerance by inhibiting As bioaccumulation, modulating the expression of As transporters and phytohormone homeostasis, leading to efficient utilization of thiol machinery for sequestration and detoxification of this toxic metalloid. The present study was aimed at investigating the influence of exogenous melatonin on the regulation of endogenous plant growth regulators and their cumulative effects on metal(loid)-binding ligands in two contrasting indica rice cultivars, viz., Khitish (arsenic sensitive) and Muktashri (arsenic tolerant) under arsenic stress. Melatonin supplementation ameliorated arsenic-induced perturbations by triggering endogenous levels of gibberellic acid and melatonin, via up-regulating the expression of key biosynthetic genes like GA3ox, TDC, SNAT and ASMT. The endogenous abscisic acid content was also enhanced upon melatonin treatment by induced expression of the key anabolic gene, NCED3 and concomitant suppression of ABA8ox1. Enhanced melatonin content induced accumulation of higher polyamines (spermidine and spermine), together with up-regulation of SPDS and SPMS in Khitish, thereby modulating stress condition. On the contrary, melatonin escalated putrescine and spermidine levels in Muktashri, via enhanced expression of ADC and SAMDC. The role of melatonin appeared to be more prominent in Khitish, as evident from better utilization of thiol components like cysteine, GSH, non-protein thiols and phytochelatins, with higher GSH/GSSG ratio, despite down-regulated expression of corresponding thiol-metabolic genes (OsMT2 and OsPCS1) to deal with arsenic toxicity. The extent of arsenic bioaccumulation, which was magnified several folds, particularly in Khitish, was decreased upon melatonin application. Overall, our observation highlighted the fact that melatonin enhanced arsenic tolerance by inhibiting arsenic bioaccumulation, via modulating the expression levels of selected arsenic transporters (OsNramp1, OsPT2, OsPT8, OsLsi1) and controlling endogenous phytohormone homeostasis, leading to efficient utilization of thiol machinery for sequestration and detoxification of this toxic metalloid.

An interlaboratory evaluation of the variability in arsenic and lead relative bioavailability when assessed using a mouse bioassay.

Animal bioassays have been developed to estimate oral relative bioavailability (RBA) of metals in soil, dust, or food for accurate health risk assessment. However, the comparability in RBA estimates from different labs remains largely unclear. Using 12 soil and soil-like standard reference materials (SRMs), this study investigated variability in lead (Pb) and arsenic (As) RBA estimates employing a mouse bioassay in 3 labs at Nanjing University, University of Jinan, and Shandong Normal University. Two performances of the bioassay at Nanjing University in 2019 and 2020 showed reproducible Pb and As RBA estimates, but increasing the number of mouse replicates in 2020 produced more precise RBA measurements. Although there were inter-lab variations in diet consumption rate and metal accumulation in mouse liver and kidneys following SRM ingestion due to differences in diet composition, bioassays at 3 labs in 2019 yielded overall similar Pb and As RBA estimates for the 12 SRMs with strong linear correlations between each 2 of the 3 labs for Pb (R2 = 0.95-0.98 and slope = 0.85-1.02) and As RBA outcomes (R2 = 0.46-0.86 and slope = 0.56-0.79). The consistency in RBA estimates was attributed to the relative nature of the final bioavailability outcome, which might overcome the inter-lab variation in diet consumption and metal uptake in mice. These results increased the confidence of use of mouse bioassays in bioavailability studies.

Contrasted tolerance of Agrostis capillaris metallicolous and non-metallicolous ecotypes in the context of a mining technosol amended by biochar, compost and iron sulfate.

Metal(loid) contamination of soil, resulting from the mining activities, is a major issue worldwide, due to its negative effects on the environment and health. Therefore, these contaminated soils need to be remediated. One realistic method is the assisted phytostabilization, which aims at establishing a vegetation cover on the soil that will reduce metal(loid) bioavailability and spreading through the prevention of wind erosion and water leaching. In addition, amendments are applied to improve soil conditions and ameliorate plant growth. In this goal, biochar and compost showed good results in terms of amelioration of soil fertility and reduction in lead bioavailability. However, they usually have a negative effect on arsenic. On the contrary, iron sulfate showed capacity to reduce arsenic mobility through interaction with its iron hydroxides. Finally, the choice of the appropriate plant species is crucial for the success of assisted phytostabilization. One good option is to use endemic species, adapted to the metal(loid) stress, with a fast growth and large shoot and root systems. The aims of this study were to (1) evaluate the effects of applying biochar, compost and iron sulfate, alone or combined, to a former mine soil on the soil properties and Agrostis capillaris growth, and (2) assess the difference between two Agrostis capillaris ecotypes, an endemic metallicolous ecotype and a non-metallicolous ecotype. Results of the mesocosm experiment showed that amendment application improved soil properties, i.e., reduced soil acidity, increased nutrient availability and lower metal(loid) stress, the best being the combination biochar-compost-iron sulfate. These ameliorations allowed a better plant growth. Finally, the metallicolous ecotype performed better in terms of growth than the non-metallicolous one and could thus be used in an assisted phytostabilization process on the former mine site.

The bioavailability of arsenic species in rice.

Rice is the principal food in many countries for billions of people and one of the most consumed cereals in the world. The rice plant has the ability to bioaccumulate essential and toxic trace elements such as arsenic. The toxicity of the elements depends not only on their concentration but also on their chemical form and their bioavailability. The inorganic forms of arsenic are more toxic than the organic forms and the toxicity increases with decreasing oxidation states. The consumers of rice in Europe who are the most exposed to inorganic arsenic are children under three, thorough diet (rice-based food). Recently, the European Commission established the maximum levels of inorganic arsenic in foodstuffs. This regulation establishes a maximum level of inorganic arsenic of 100 µg kg-1 in rice destined for the production of food for infants and young children. In order to know the relation between the As ingested and the arsenic absorbed, studies of bioavailability are necessary. We proposed an in vitro digestion method with dialysis to estimate this relation. Furthermore, a bioavailability study of As species in rice was performed in order to know if a change in As species occurred during the gastrointestinal digestion process. Arsenic species were determined in rice and in the dialysate fraction by high-performance liquid chromatography coupled to inductively coupled plasma mass spectrometry (HPLC-ICP-MS). The proposed method has been applied to different rice samples acquired in the local Spanish market. Graphical abstract.

Arsenic exposure: A public health problem leading to several cancers.

Arsenic, a metalloid and naturally occurring element, is one of the most abundant elements in the earth's crust. Water is contaminated by arsenic through natural sources (underground water, minerals and geothermal processes) and anthropogenic sources such as mining, industrial processes, and the production and use of pesticides. Humans are exposed to arsenic mainly by drinking contaminated water, and secondarily through inhalation and skin contact. Arsenic exposure is associated with the development of vascular disease, including stroke, ischemic heart disease and peripheral vascular disease. Also, arsenic increases the risk of tumors of bladder, lungs, kidneys and liver, according to the International Agency for Research on Cancer and the Food and Drug Administration. Once ingested, an estimated 70-90% of inorganic arsenic is absorbed by the gastrointestinal tract and widely distributed through the blood to different organs, primarily to the liver, kidneys, lungs and bladder and secondarily to muscle and nerve tissue. Arsenic accumulates in the organs, especially in the liver. Its excretion mostly takes place through urination. The toxicokinetics of arsenic depends on the duration of exposure, pathway of ingestion, physicochemical characteristics of the compound, and affected biological species. The present review outlines of arsenic toxic effects focusing on different cancer types whit highest prevalence's by exposure to this metalloid and signaling pathways of carcinogenesis.

Environmental exposure of arsenic and fluoride and their combined toxicity: A recent update.

Environmental exposure to arsenic (As) and fluoride (F) in the recent year has been increased because of excessive use of naturally contaminated ground water. Surface water is also regularly contaminated with these elements in various industrial areas. Arsenicosis and fluorosis upon individual exposure of As and F are reported in many studies. A syndrome of endemic As poisoning and fluorosis occurs during concurrent exposure of As and F. Previous reports showed synergistic, antagonistic and independent effects of these two compounds, although few recent reports also revealed antagonistic effects after co-exposure. Interaction during intestinal absorption and influence of F on As metabolism might be the cause of antagonism. The synergism/antagonism is thought to depend on the dose and duration of the co-exposure. However, the detailed mechanism is still not fully understood and needs further studies. Removal technologies of As and F from contaminated water is available but removal of such contaminants from food is yet to be developed. Antioxidants are useful to mitigate the toxic effects of As and F. This review focused on the effect of co-exposure, amelioration as well as removal techniques of As and F.

A rice glutaredoxin regulate the expression of aquaporin genes and modulate root responses to provide arsenic tolerance.

Rice is the most consumed food crop and essential determinant in global food security program. Currently, arsenic (As) accumulation in rice is a critical concern in terms of both crop productivity and grain quality; therefore, it is an urgent need to reduce As accumulation. Here, we selected a glutaredoxin (OsGrx_C7) gene that plays an essential role in AsIII tolerance in rice. To explore the mechanism, we raised OsGrx_C7 overexpression (OE) rice lines, which showed improved plant AsIII tolerance and lowered its accumulation in grains. Arsenic accumulation in husk, unpolished, and polished rice reduced by ca. 65%, 67%, and 85%, respectively, in OE lines, compared to wild-type (WT) plants. To know the rationale, expression of AsIII transporters (aquaporins) in root and shoot tissues were examined, and revealed that OsGrx_C7 regulates the expression of these genes, which ultimately reduces root to shoot AsIII translocation. Additionally, OsGrx_C7 improves root growth by regulating the expression of oxidative stress-induced root expansion related genes, promote root growth and plant health. Overall, current study suggested that AsIII induced OsGrx_C7 markedly enhanced tolerance to AsIII with reduced accumulation in grains by regulating root expansion and controlling root to shoot As transport by altered expression of AsIII aquaporins.

Consequences of trace metal cocktail exposure in zebra finch (Taeniopygia guttata) and effect of calcium supplementation.

Trace metal elements are significant stressors in urban areas. Their harmful effects on physiological parameters are demonstrated, but current laboratory studies are not representative of wild chronic exposure to a trace metal cocktail. Calcium can reduce the accumulation and toxicity of several metals, but soil acidification in cities leads to a decrease in bioavailability of this element. The objective of this study was to investigate the accumulation and toxicity of a trace metal cocktail representative of urban exposure on passerine birds, and test the importance of calcium availability on these toxic effects. We exposed zebra finches (Taeniopygia guttata) to a cocktail of seven metals and one metalloid in drinking water, with or without calcium supplementation. We monitored the concentration of metals in the blood and feathers, and their effects on oxidative status and telomere length. The metal cocktail led to higher concentration of all elements in the feathers, and of arsenic and lead in the blood. Birds with a higher concentration of cadmium, arsenic and lead in the feathers had shorter telomeres, but no impact of the cocktail was detected on oxidative status. Birds of the 'calcium' group and the 'calcium and metal' group accumulated higher concentrations of zinc, chromium and nickel in feathers. The 'calcium and metal' group also accumulated lower concentrations of arsenic and lead in feathers compared to the 'metal' group. Our results suggest that chronic exposure to a cocktail of metals at low concentrations has deleterious effects on birds, which can be limited through calcium intake.

Assessment of the risk associated with mining-derived arsenic inputs in a lagoon system.

Southern Mediterranean lagoons are considered among the systems most vulnerable to anthropogenic activities. In its present condition, the Mar Menor lagoon in south-eastern Spain must be considered as degraded as a result of the pressures to which its shoreline is exposed. These include the transport of arsenic from nearby mining areas, linked to soluble or particulate run-off following rainfall events and flooding. This work studies the solubility and bioavailability of arsenic in the soils of watercourses that drain into the Mar Menor, using nine single chemical extractions with different reagents. The values obtained for As, as well as for Fe and Mn, throw light on the interactions of these metals with As and predict future behaviour patterns for different scenarios. The mineral composition is seen to significantly influence the mobility of the studied elements and shows the relation between the soils and materials of mining origin. It has been suggested that the sediments deposited in the in the watercourses or "ramblas" that transport these materials may act as foci of dispersion.

Pteridophytes in phytoremediation.

Soil contamination by heavy metals and metalloids is a serious problem which needs to be addressed. There are several methods for removal of contaminants, but they are costly, while the method of phytoremediation is eco-friendly and cost-effective. Pteridophytes have been found to remediate heavy metal-contaminated soil. Pteridophytes are non-flowering plant that reproduces by spores. Pteris vittata has been reported as the first fern plant to hyperaccumulate arsenic. The Pteris species belongs to the order Pteridales. Other ferns that are known phytoremediators are, for example, Nephrolepis cordifolia and Hypolepis muelleri (identified as phytostabilisers of Cu, Pb, Zn and Ni); similarly Pteris umbrosa and Pteris cretica accumulate arsenic in leaves. So, pteridophytes have a number of species that accumulate contaminants. Many of them have been identified, while various other are being explored. The present review article describes the phytoremediation potential of pteridophytes plants and suggests as a potential asset for phytoremediation programs.

Heavy metal assimilation in maize (Zea mays L.) plants growing near mine tailings.

Mining is one of the main economic activities in Mexico, and Hidalgo State is one of the main areas; however, this activity produces wastes, such as mine tailings, that are disposed in deposits and may be dispersed on the soils (e.g., agricultural soils). In this study, the concentrations of As and heavy metals in maize plants cultivated in a greenhouse in two soils influenced by tailings were evaluated. Plants were grown for 165 days in the soils (one of them more polluted due to a closer distance to the tailings) and one control soil close to the study zone. Plants' growth was evaluated, and after harvesting, they were divided in six parts: root, stalk, plant leaves, cob sheath, corncob and grains. Plants showed depressed development: small height, slow growth and physiological cob immaturity. Assimilation of As and heavy metals by plants was influenced by the concentration of the contaminants but also by the availability of nutrients. Important concentrations of the metals were recorded in the harvestable parts (grain, stalk and cob sheath). The order of accumulation was Zn > Fe > Pb > As > Cd. Cadmium was not detected in grains, but a maximum concentration of As at 1.02 mg/kg and Pb at 3.9 mg/kg was measured in the dry grain. These As and Pb concentrations do not comply with CODEX Alimentarius standards for maize, which states that the cob must be free of heavy metals. In addition, Pb also exceeds the limits established by the Mexican NOM-247-SSA1-2008 regulation.

Arsenic in the rock-soil-plant system and related health risk in a magmatic-metamorphic belt, West of Iran.

Following earlier reports of water contamination and arsenic (As) toxicity symptoms in residents of Kurdistan Province, As was determined in rock, soil and plant samples to investigate its fate from rock to crops and its potential effects on human health. Total As content ranged from 4.9 to 10,000 mg/kg, 7.7-430 mg/kg and < 0.05-25,079 µg/kg (dry weight) in rock, soil and plant samples, respectively. The Qorveh-Bijar region data indicated that magmatic differentiation has enriched late magmatic fluids in As. High rare earth elements concentration, dissociation coefficient, and positive Eu anomaly in volcanic rocks, indicated the prevalence of intermediate to felsic composition. The highest As concentration was measured in travertine. In soil, As average level in Qorveh and Bijar was 48.5 and 107 mg/kg, respectively. Higher pollution index and geoaccumulation index (Igeo) were also calculated for Bijar County. The As concentration in crop samples was greater than the recommended maximum permissible concentration for foodstuff. Mann-Whitney U test revealed significant differences between As concentration in different plant species and no difference between plants in Bijar and Qorveh. Also, alfalfa displayed the highest biological accumulation coefficient among the investigated plants. The calculated chronic daily intake of As in Bijar County was higher than the recommended levels for wheat and barley grains. Moreover, the hazard quotient (HQ) and incremental lifetime cancer risk assessments revealed high non-cancer (HQ > 1 for both adults and children) and cancer (particularly for barley in Bijar) risks for inhabitants via consumption of As contaminated crops cultivated in the study area.

Differential distribution of and similar biochemical responses to different species of arsenic and antimony in Vetiveria zizanioides.

Vetiver grass (Vetiveria zizanioides L. Nash) has a great application potential to the phytoremediation of heavy metals pollution. However, few studies explored the bioavailability and distribution of different speciations of As and Sb in V. zizanioides. This study aimed to clarify the allocation and accumulation of two inorganic species arsenic (As(III) and As(V)) and antimony (Sb(III) and Sb(V)) in V. zizanioides, to understand the self-defense mechanisms of V. zizanioides to these metal(loids) elements. Thus, an experiment was conducted under greenhouse conditions to identify distribution of As and Sb in plant roots and shoots. Antioxidant enzymes (superoxide dismutase, SOD) and changes of subcellular structures were tested to evaluate metal(loids) tolerance capacities of V. zizanioides. This study demonstrated that V. zizanioides had higher capacity to accumulate Sb than As. For Sb absorption, Sb(III) content is significantly higher than Sb(V) in tissues of V. zizanioides under all concentration levels, despite the oxidation of Sb(III) on the nutrient solution surface. Additional Sb was mainly accumulated in plant roots due to Sb immobilization by transforming it into precipitates. As was more easily transferred to aerial tissues and had low accumulation rates, probably due to its restricted uptake rather than restricted transport. In many cases, two inorganic species of As and Sb showed almost same biotoxicity to V. zizanioides estimated from its biomass, SOD activity, and MDA content as well as functional groups. In summary, the results of this study provide new insights into understanding allocation, accumulation and phytotoxicity effects of arsenic and antimony in V. zizanioides. Schematic diagram of distribution of and biochemical responses to As(III), As(V), Sb(III), and Sb(V) in tissue of V. zizanioides.

Comparative transcriptome profiling reveals the reprogramming of gene networks under arsenic stress in Indian mustard.

Arsenic is a widespread toxic metalloid that is classified as a class I carcinogen known to cause adverse health effects in humans. In the present study, we investigated arsenic accumulation potential and comparative gene expression in Indian mustard. The amount of arsenic accumulated in shoots varied in the range of 15.99-1138.70 mg/kg on a dry weight basis among five cultivars. Comparative expression analysis revealed 10 870 significantly differentially expressed genes mostly belonging to response to stress, metabolic processes, signal transduction, transporter activity, and transcription regulator activity to be up-regulated, while most of the genes involved in photosynthesis, developmental processes, and cell growth were found to be down-regulated in arsenic-treated tissues. Further, pathway analysis using the KEGG Automated Annotation server (KAAS) revealed a large-scale reprogramming of genes involved in genetic and environmental information processing pathways. Top pathways with maximum KEGG orthology hits included carbon metabolism (2.5%), biosynthesis of amino acids (2.1%), plant hormone signal transduction (1.4%), and glutathione metabolism (0.6%). A transcriptomic investigation to understand the arsenic accumulation and detoxification in Indian mustard will not only help to improve its phytoremediation efficiency but also add to the control measures required to check bioaccumulation of arsenic in the food chain.

Differential metabolism of inorganic arsenic in mice from genetically diverse Collaborative Cross strains.

Mice have been frequently used to study the adverse effects of inorganic arsenic (iAs) exposure in laboratory settings. Like humans, mice metabolize iAs to monomethyl-As (MAs) and dimethyl-As (DMAs) metabolites. However, mice metabolize iAs more efficiently than humans, which may explain why some of the effects of iAs reported in humans have been difficult to reproduce in mice. In the present study, we searched for mouse strains in which iAs metabolism resembles that in humans. We examined iAs metabolism in male mice from 12 genetically diverse Collaborative Cross (CC) strains that were exposed to arsenite in drinking water (0.1 or 50 ppm) for 2 weeks. Concentrations of iAs and its metabolites were measured in urine and livers. Significant differences in total As concentration and in proportions of total As represented by iAs, MAs, and DMAs were observed between the strains. These differences were more pronounced in livers, particularly in mice exposed to 50 ppm iAs. In livers, large variations among the strains were found in percentage of iAs (15-48%), MAs (11-29%), and DMAs (29-66%). In contrast, DMAs represented 96-99% of total As in urine in all strains regardless of exposure. Notably, the percentages of As species in urine did not correlate with total As concentration in liver, suggesting that the urinary profiles were not representative of the internal exposure. In livers of mice exposed to 50 ppm, but not to 0.1 ppm iAs, As3mt expression correlated with percent of iAs and DMAs. No correlations were found between As3mt expression and the proportions of As species in urine regardless of exposure level. Although we did not find yet a CC strain in which proportions of As species in urine would match those reported in humans (typically 10-30% iAs, 10-20% MAs, 60-70% DMAs), CC strains characterized by low %DMAs in livers after exposure to 50 ppm iAs (suggesting inefficient iAs methylation) could be better models for studies aiming to reproduce effects of iAs described in humans.