Arsenic (As) levels in particulate matter (PM) are routinely monitored in cities of developed countries. Despite advances in the knowledge of its inorganic species in PM in urban areas, organic species are often overlooked with no information on their behaviour in urban parks - areas with increased potential for As biomethylation. Therefore, the aim of this study was to characterize As distribution, bioaccessibility, seasonal variation and speciation (AsIII, AsV, MMA, DMA and TMAO) in PMx-PM10 of an urban park. Two sites with different distance from the road were selected for winter and summer sampling. From the PM samples, we gravimetrically determined PM10 concentrations in the air and via ICP-MS the total As content there. To assess the portion of bioaccessible As, water extractable As content was analysed. Simultaneously, the As species in PM10 water extracts were analysed via coupling of HPLC with ICP-MS method. There was no seasonal difference in PM10 concentration in the park, probably due to the increased summer PM load related to recreational activities in the park and park design. Spatial distribution of total As in PM10 and As fractional distribution in PMx suggested that As mostly didn\'t originate from traffic although highest As content was observed in the fine fraction (PM2.5) related to combustion processes. However, significant winter increase of As (determined by AsIII and AsV) despite the unchanged concentration of PM10 indicated a decisive influence of household heating-related combustion and possibly influence of reduced vegetation density. As present in the PM10 was mostly in bioaccessible form. Seasonal influence of As biomethylation was clearly demonstrated on the TMAO specie during the summer campaign. Except the significant summer TMAO increase, the results also indicated the biomethylation influence on DMA. Therefore, an increased risk of exposure to organic As species in urban parks can be expected during summer.

Targeting overexpressed thioredoxin reductase (TrxR) in cancer cells to induce oxidative stress has been proved to be an effective strategy for cancer therapy. However, the treatment was hindered by the low efficiency and frequent administration of TrxR inhibitors, and hence more potent TrxR inhibitors were urgently needed. Herein, we designed and synthesized a series of TrxR inhibitors based on arsenicals. Among these, compound 1d inhibited the proliferation of a variety of cancer cells at low micromolar concentrations and exhibited low toxicity to normal cells. Importantly, compound 1d induced the accumulation of reactive oxygen species (ROS) by inhibiting the TrxR activity, further causing the collapse of the redox system, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and DNA damage, followed by oxidative stress-induced cell apoptosis. In vivo data showed that, compared with the clinical TrxR inhibitor auranofin (AUR), compound 1d could more effectively eliminate tumors by 90 % at a dose of 1.5 mg/kg without any obvious side effects. These results indicated that compound 1d was a potent TrxR inhibitor against cancer.

Arsenic is a hazardous heavy metalloid that imposes threats to human health globally. It is widely spread throughout the environment in various forms. Arsenic-based compounds are either inorganic compounds (iAs) or organoarsenicals (oAs), where the latter are biotically generated from the former. Exposure to arsenic-based compounds results in varying biochemical derangements in living systems, leading eventually to toxic consequences. One important target for arsenic in biosystems is the network of metabolic enzymes, especially the superfamily of cytochrome P450 enzymes (CYPs) because of their prominent role in both endobiotic and xenobiotic metabolism. Therefore, the alteration of the CYPs by different arsenicals has been actively studied in the last few decades. We have previously summarized the findings of former studies investigating arsenic associated modulation of different CYPs in human experimental models. In this review, we focus on non-human models to get a complete picture about possible CYPs alterations in response to arsenic exposure.

Arsenic is methylated by arsenite (As(III)) S-adenosylmethionine (SAM) methyltransferases (ArsMs). ArsM crystal structures show three domains (an N-terminal SAM binding domain (A domain), a central arsenic binding domain (B domain), and a C-terminal domain of unknown function (C domain)). In this study, we performed a comparative analysis of ArsMs and found a broad diversity in structural domains. The differences in the ArsM structure enable ArsMs to have a range of methylation efficiencies and substrate selectivities. Many small ArsMs with 240-300 amino acid residues have only A and B domains, represented by RpArsM from Rhodopseudomonas palustris. These small ArsMs have higher methylation activity than larger ArsMs with 320-400 residues such as Chlamydomonas reinhardtii CrArsM, which has A, B, and C domains. To examine the role of the C domain, the last 102 residues in CrArsM were deleted. This CrArsM truncation exhibited higher As(III) methylation activity than the wild-type enzyme, suggesting that the C-terminal domain has a role in modulating the rate of catalysis. In addition, the relationship of arsenite efflux systems and methylation was examined. Lower rates of efflux led to higher rates of methylation. Thus, the rate of methylation can be modulated in multiple ways.

Edible seaweed consumption is an essential route of human exposure to complex organoarsenicals, including arsenosugars and arsenosugar phospholipids. However, the effects of gut microbiota on the metabolism and bioavailability of arsenosugars in vivo are unknown. Herein, two nori and two kelp samples with phosphate arsenosugar and sulfonate arsenosugar, respectively, as the predominant arsenic species, were administered to normal mice and gut microbiota-disrupted mice treated with the broad-spectrum antibiotic cefoperazone for 4 weeks. Following exposure, the community structures of the gut microbiota, total arsenic concentrations, and arsenic species in excreta and tissues were analyzed. Total arsenic excreted in feces and urine did not differ significantly between normal and antibiotic-treated mice fed with kelp samples. However, the total urinary arsenic of normal mice fed with nori samples was significantly higher (p < 0.05) (urinary arsenic excretion factor, 34-38 vs 5-7%), and the fecal total arsenic was significantly lower than in antibiotic-treated mice. Arsenic speciation analysis revealed that most phosphate arsenosugars in nori were converted to arsenobetaine (53.5-74.5%) when passing through the gastrointestinal tract, whereas a large portion of sulfonate arsenosugar in kelp was resistant to speciation changes and was excreted in feces intact (64.1-64.5%). Normal mice exhibited greater oral bioavailability of phosphate arsenosugar from nori than sulfonate arsenosugar from kelp (34-38 vs 6-9%). Our work provides insights into organoarsenical metabolism and their bioavailability in the mammalian gut.

Paracoccus denitrificans ArsH is encoded by two identical genes located in two distinct putative arsenic resistance (ars) operons. Escherichia coli-produced recombinant N-His6-ArsH was characterized both structurally and kinetically. The X-ray structure of ArsH revealed a flavodoxin-like domain and motifs for the binding of flavin mononucleotide (FMN) and reduced nicotinamide adenine dinucleotide phosphate (NADPH). The protein catalyzed FMN reduction by NADPH via ternary complex mechanism. At a fixed saturating FMN concentration, it acted as an NADPH-dependent organoarsenic reductase displaying ping-pong kinetics. A 1:1 enzymatic reaction of phenylarsonic acid with the reduced form of FMN (FMNH2) and formation of phenylarsonous acid were observed. Growth experiments with P. denitrificans and E. coli revealed increased toxicity of phenylarsonic acid to cells expressing arsH, which may be related to in vivo conversion of pentavalent As to more toxic trivalent form. ArsH expression was upregulated not only by arsenite, but also by redox-active agents paraquat, tert-butyl hydroperoxide and diamide. A crucial role is played by the homodimeric transcriptional repressor ArsR, which was shown in in vitro experiments to monomerize and release from the DNA-target site. Collectively, our results establish ArsH as responsible for enhancement of organo-As(V) toxicity and demonstrate redox control of ars operon.

Pollution and poisoning with carcinogenic arsenic (As) is of major concern globally. Interestingly, there are ferns that can naturally tolerate remarkably high As concentrations in soils while hyperaccumulating this metalloid in their fronds. Besides Pteris vittata in which As-related traits and molecular determinants have been studied in detail, the As hyperaccumulation status has been attributed also to Pteris cretica. We thus inspected two P. cretica cultivars, Parkerii and Albo-lineata, for As hyperaccumulation traits. The cultivars were grown in soils supplemented with 20, 100, and 250 mg kg-1 of inorganic arsenate (iAsV). Unlike Parkerii, Albo-lineata was confirmed to be As tolerant and hyperaccumulating, with up to 1.3 and 6.4 g As kg-1 dry weight in roots and fronds, respectively, from soils amended with 250 mg iAsV kg-1. As speciation analyses rejected that organoarsenical species and binding with phytochelatins and other proteinaceous ligands would play any significant role in the biology of As in either cultivar. While in Parkerii, the dominating As species, particularly in roots, occurred as iAsV, in Albo-lineata the majority of the root and frond As was apparently converted to iAsIII. Parkerii markedly accumulated iAsIII in its fronds when grown on As spiked soils. Considering the roles iAsV reductase ACR2 and iAsIII transporter ACR3 may have in the handling of iAs, we isolated Albo-lineata PcACR2 and PcACR3 genes closely related to P. vittata PvACR2 and PvACR3. The gene expression analysis in Albo-lineata fronds revealed that the transcription of PcACR2 and PcACR3 was clearly As responsive (up to 6.5- and 45-times increase in transcript levels compared to control soil conditions, respectively). The tolerance and uptake assays in yeasts showed that PcACRs can complement corresponding As-sensitive mutations, indicating that PcACR2 and PcACR3 encode functional proteins that can perform, respectively, iAsV reduction and membrane iAsIII transport tasks in As-hyperaccumulating Albo-lineata.

Sea dumping of chemical warfare (CW) took place worldwide during the 20th century. Submerged CW included metal bombs and casings that have been exposed for 50-100 years of corrosion and are now known to be leaking. Therefore, the arsenic-based chemical warfare agents (CWAs), pose a potential threat to the marine ecosystems. The aim of this research was to support a need for real-data measurements for accurate risk assessments and categorization of threats originating from submerged CWAs. This has been achieved by providing a broad insight into arsenic-based CWAs acute toxicity in aquatic ecosystems. Standard tests were performed to provide a solid foundation for acute aquatic toxicity threshold estimations of CWA: Lewisite, Adamsite, Clark I, phenyldichloroarsine (PDCA), CWA-related compounds: TPA, arsenic trichloride and four arsenic-based CWA degradation products. Despite their low solubility, during the 48 h exposure, all CWA caused highly negative effects on Daphnia magna. PDCA was very toxic with 48 h D. magna LC50 at 0.36 μg × L-1 and Lewisite with EC50 at 3.2 μg × L-1. Concentrations at which no immobilization effects were observed were slightly above the analytical Limits of Detection (LOD) and Quantification (LOQ). More water-soluble CWA degradation products showed no effects at concentrations up to 100 mg × L-1.

Organoarsenicals such as roxarsone (ROX) pose a great threat to the eco-environment and human health. Herein, the degradation of ROX via UV-based advanced oxidation processes (AOPs) including UV/hydrogen peroxide (UV/H2O2), UV/peroxydisulfate (UV/PDS), and UV/peroxymonosulfate (PMS) processes are comparatively investigated. The removal efficiency of ROX in the UV-based AOPs follows the order of UV/H2O2 >UV/PDS>UV/PMS at pH 7.0, while UV/PDS is the most effective process in reducing the total organic carbon (TOC). The second-order rate constants of ROX with hydroxyl radicals (•OH) and sulfate radicals (SO4•-) are determined to be (2.71 ± 0.27)× 109 and (7.68 ± 0.37)× 108 M-1s-1, respectively. The degradation of ROX obeys the pseudo-first-order kinetics model, and the apparent rate constants (k) linearly increase with increasing the oxidants dosage from 0.10 to 1.0 mM. The solution pH (5.0-11.0) exhibits a limited effect on the oxidation of ROX in UV/H2O2 and UV/PDS processes, but a great enhancement is observed at pH 11.0 in UV/PMS process. Humic acid and bicarbonate obviously suppress the photodegradation of ROX. In addition, arsenic in ROX is mainly converted to As(V) in the three UV-based AOPs. Overall, this study provides essential information for the degradation of ROX via the traditional UV-based AOPs.

Up to now, complicated organoarsenicals were mainly identified in marine organisms, suggesting that these organisms play a critical role in arsenic biogeochemical cycling because of low phosphate and relatively high arsenic concentration in the marine environment. However, the response of marine macroalgae to inorganic arsenic remains unknown. In this study, Pyropia haitanensis were exposed to arsenate [As(V)] (0.1, 1, 10, 100 μM) or arsenite [As(III)] (0.1, 1, 10 μM) under laboratory conditions for 3 d. The species of water-soluble arsenic, the total concentration of lipid-soluble and cell residue arsenic of the algae cells was analyzed. As(V) was mainly transformed into oxo-arsenosugar-phosphate, with other arsenic compounds such as monomethylated, As(III), demethylated arsenic and oxo-arsenosugar-glycerol being likely the intermediates of arsenosugar synthesis. When high concentration of As(III) was toxic to P. haitanensis, As(III) entered into the cells and was transformed into less toxic organoarsenicals and As(V). Transcriptome results showed genes involved in DNA replication, mismatch repair, base excision repair, and nucleotide excision repair were up-regulated in the algae cells exposed to 10 μM As(V), and multiple genes involved in glutathione metabolism and photosynthetic were up-regulated by 1 μM As(III). A large number of ABC transporters were down-regulated by As(V) while ten genes related to ABC transporters were up-regulated by As(III), indicating that ABC transporters were involved in transporting As(III) to vacuoles in algae cells. These results indicated that P. haitanensis detoxifies inorganic arsenic via transforming them into organoarsenicals and enhancing the isolation of highly toxic As(III) in vacuoles.