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At least 811 records · Page 45Linked to original sources
PubMed2004

TCLP underestimates leaching of arsenic from solid residuals under landfill conditions.

Recent revision of the arsenic in drinking water standard will cause many utilities to implement removal technologies. Most of the affected utilities are expected to use adsorption onto solid media for arsenic removal. The arsenic-bearing solid residuals (ABSR) from adsorption processes are to be disposed of in nonhazardous landfills. The Toxicity Characteristic Leaching Procedure (TCLP) tests whether a waste is hazardous or nonhazardous; most solid residuals pass the TCLP. However, the TCLP poorly simulates the alkaline pH, low redox potential, biological activity, long retention time, and organic composition of mature landfills. These same conditions are likely to favor mobilization of arsenic from metal oxide sorbents. This study quantifies leaching of arsenic from Activated Alumina (AA) and Granular Ferric Hydroxide (GFH), two sorbents expected to be widely used for arsenic removal. The sorbents were subjected to the TCLP, the Waste Extraction Test (WET), an actual landfill leachate, and two synthetic leachate solutions. Up to tenfold greater arsenic concentration is extracted by an actual landfill leachate than by the TCLP. Equilibrium leachate concentrations are not achieved within 18 h (the TCLP duration) and an N2 headspace and end-over-end tumbling increase the rate of arsenic mobilization. However, tests with actual landfill leachate indicate the WET may also underestimate arsenic mobilization in landfills.

Adsorption↗
PubMed2005

Ineffectiveness and poor reliability of arsenic removal plants in West Bengal, India.

In the recent past, arsenic contamination in groundwater has emerged as an epidemic in different Asian countries, such as Bangladesh, India, and China. Arsenic removal plants (ARP) are one possible option to provide arsenic-safe drinking water. This paper evaluates the efficiency of ARP projects in removing arsenic and iron from raw groundwater, on the basis of our 2-year-long study covering 18 ARPs from 11 manufacturers, both from home and abroad, installed in an arsenic affected area of West Bengal, India, known as the Technology Park Project (TP project). Immediately after installation of ARPs on August 29, 2001, the villagers began using filtered water for drinking and cooking, even though our first analysis on September 13, 2001 found that 10 of 13 ARPs failed to remove arsenic below the WHO provisional guideline value (10 microg/L), while six plants could not achieve the Indian Standard value (50 microg/L). The highest concentration of arsenic in filtered water was observed to be 364 microg/L. Our 2-year study showed that none of the ARPs could maintain arsenic in filtered water below the WHO provisional guideline value and only two could meet the Indian standard value (50 microg/L) throughout. Standard statistical techniques showed that ARPs from the same manufacturers were not equally efficient. Efficiency of the ARPs was evaluated on the basis of point and interval estimates of the proportion of failure. During the study period almost all the ARPs have undergone minor or major modifications to improve their performance, and after our study, 15 (78%) out of 18 ARPs were no longer in use. In this study, we also analyzed urine samples from villagers in the TP project area and found that 82% of the samples contained arsenic above the normal limit.

Arsenic↗
PubMed2004

Arsenic and lead leaching from the waste derived fertilizer ironite.

The toxicity characteristic leaching procedure (TCLP) and the synthetic precipitation leaching procedure (SPLP) were performed on commercially purchased samples of the waste-derived soil amendment marketed as Ironite. Ten samples of the 1-0-0 grade (the most widely available in Florida) were tested. Two samples of the 12-10-10 grade and three samples of the 6-2-1 grade (a liquid version) were tested as well. TCLP leachate concentrations from the 1-0-0 grade samples ranged from 5.0 to 8.0 mg L(-1) for lead and 2.2 to 4.8 mg L(-1) for arsenic. SPLP concentrations from the 1-0-0 samples ranged from 0.62 to 3.1 mg L(-1) for lead and 1.9 to 8.2 mg L(-1) for arsenic. All of the 1-0-0 grade samples exceeded the U.S. hazardous waste toxicity characteristic (TC) limit for lead (5 mg L(-1)), while five of the 10 SPLP samples exceeded the TC limit for arsenic (5 mg L(-1)). The greater arsenic leachability in the SPLP relative to the TCLP was determined to be a result of lower pH conditions in the SPLP. A composite sample of the 1-0-0 grade was found to leach much greater concentrations of both arsenic and lead using California's waste extraction test (WET). Lead leachate concentrations were much lower in the two 12-10-10 samples (0.03 mg L(-1) or less); arsenic concentrations in these leachates (both TCLP and SPLP) exceeded 5 mg L(-1). None of the 6-2-1 samples contained lead or arsenic above TC limits. An experiment performed on the 1-0-0 grade which examined leachability as a function of pH found that at pH values in the range of what is encountered in the human digestive system (pH 4.0 to 1.5) lead leached 2-36% of its initial content, and arsenic leached 1-6% of its initial content. A simple gastric acid leaching experiment found 83 and 37% of the lead and arsenic present to leach, respectively.

Arizona↗
PubMed2005

Bacterial bioassay for rapid and accurate analysis of arsenic in highly variable groundwater samples.

In this study, we report the first ever large-scale environmental validation of a microbial reporter-based test to measure arsenic concentrations in natural water resources. A bioluminescence-producing arsenic-inducible bacterium based on Escherichia coli was used as the reporter organism. Specific protocols were developed with the goal to avoid the negative influence of iron in groundwater on arsenic availability to the bioreporter cells. A total of 194 groundwater samples were collected in the Red River and Mekong River Delta regions of Vietnam and were analyzed both by atomic absorption spectroscopy (AAS) and by the arsenic bioreporter protocol. The bacterial cells performed well at and above arsenic concentrations in groundwater of 7 microg/L, with an almost linearly proportional increase of the bioluminescence signal between 10 and 100 microg As/L (r2 = 0.997). Comparisons between AAS and arsenic bioreporter determinations gave an overall average of 8.0% false negative and 2.4% false positive identifications for the bioreporter prediction at the WHO recommended acceptable arsenic concentration of 10 microg/L, which is far betterthan the performance of chemical field test kits. Because of the ease of the measurement protocol and the low application cost, the microbiological arsenic test has a great potential in large screening campaigns in Asia and in other areas suffering from arsenic pollution in groundwater resources.

Arsenic↗
PubMed2006

Release of arsenic to the environment from CCA-treated wood. 2. Leaching and speciation during disposal.

Wood treated with chromated copper arsenate (CCA) is primarily disposed within construction and demolition (C&D) debris landfills, with wood monofills and municipal solid waste (MSW) landfills as alternative disposal options. This study evaluated the extent and speciation of arsenic leaching from landfills containing CCA-treated wood. In control lysimeters where untreated wood was used, dimethylarsinic acid (DMAA) represented the major arsenic species. The dominant arsenic species differed in the lysimeters containing CCA-treated wood, with As(V) greatest in the monofill and C&D lysimeters and As(III) greatest in the MSW lysimeters. In CCA-containing lysimeters, the organoarsenic species monomethylarsonic acid (MMAA) and DMAAwere virtually absent in the monofill lysimeter and observed in the C&D and MSW lysimeters. Overall arsenic leaching rate varied for the wood monofill (0.69% per meter of water added), C&D (0.36% per m), and MSW (0.84% per m) lysimeters. Utilizing these rates with annual disposal data, a mathematical model was developed to quantify arsenic leaching from CCA-treated wood disposed to Florida landfills. Model findings showed between 20 and 50 t of arsenic (depending on lysimeter type) had leached prior to 2000 with an expected increase between 350 and 830 t by 2040. Groundwater analysis from 21 Florida C&D landfills suspected of accepting CCA-treated wood showed that groundwater at 3 landfills was characterized by elevated arsenic concentrations with only 1 showing impacts from the C&D waste. The slow release of arsenic from disposed treated wood may account for the lack of significant impact to groundwater near most C&D facilities at this time. However, greater impacts are anticipated in the future given that the maximum releases of arsenic are expected by the year 2100.

Arsenates↗
PubMed2006

Modeling the probability of arsenic in groundwater in New England as a tool for exposure assessment.

We developed a process-based model to predict the probability of arsenic exceeding 5 microg/L in drinking water wells in New England bedrock aquifers. The model is being used for exposure assessment in an epidemiologic study of bladder cancer. One important study hypothesis that may explain increased bladder cancer risk is elevated concentrations of inorganic arsenic in drinking water. In eastern New England, 20-30% of private wells exceed the arsenic drinking water standard of 10 micrograms per liter. Our predictive model significantly improves the understanding of factors associated with arsenic contamination in New England. Specific rock types, high arsenic concentrations in stream sediments, geochemical factors related to areas of Pleistocene marine inundation and proximity to intrusive granitic plutons, and hydrologic and landscape variables relating to groundwater residence time increase the probability of arsenic occurrence in groundwater. Previous studies suggest that arsenic in bedrock groundwater may be partly from past arsenical pesticide use. Variables representing historic agricultural inputs do not improve the model, indicating that this source does not significantly contribute to current arsenic concentrations. Due to the complexity of the fractured bedrock aquifers in the region, well depth and related variables also are not significant predictors.

Arsenic↗
PubMed2000

Total and inorganic arsenic in fresh and processed fish products.

Total arsenic and inorganic arsenic contents were determined in 153 samples of seafood products consumed in the Basque Country (Spain): fish (white fish and blue fish), mollusks, crustaceans, and preserved fish. White fish presented higher levels of total arsenic and lower levels of inorganic arsenic than the blue fish, indicating possible differences in the metabolization of inorganic arsenic. For total arsenic, 66% of the samples exceeded the maximum permitted level by the strictest international legislation in seafood products [1 microg g(-)(1), wet weight (ww)]. The levels of inorganic arsenic were considerably lower than the maximum authorized in New Zealand (2 microg g(-)(1), ww), the only country with legislation for inorganic arsenic in fish and fish products. It is recommended that legislation based on levels of inorganic arsenic should be established.

Arsenic↗
PubMed2001

Methylated trivalent arsenic species are genotoxic.

The reactivities of methyloxoarsine (MAs(III)) and iododimethylarsine (DMAs(III)), two methylated trivalent arsenicals, toward supercoiled phiX174 RFI DNA were assessed using a DNA nicking assay. The induction of DNA damage by these compounds in vitro in human peripheral lymphocytes was assessed using a single-cell gel (SCG, "comet") assay. Both methylated trivalent arsenicals were able to nick and/or completely degrade phiX174 DNA in vitro in 2 h incubations at 37 degrees C (pH 7.4) depending on concentration. MAs(III) was effective at nicking phiX174 DNA at 30 mM; however, at 150 microM DMAs(III), nicking could be observed. Exposure of phiX174 DNA to sodium arsenite (iAs(III); from 1 nM up to 300 mM), sodium arsenate (from 1 microM to 1 M), and the pentavalent arsenicals, monomethylarsonic acid (from 1 microM to 3 M) and dimethylarsinic acid (from 0.1 to 300 mM), did not nick or degrade phiX174 DNA under these conditions. In the SCG assay in human lymphocytes, methylated trivalent arsenicals were much more potent than any other arsenicals that were tested. On the basis of the slopes of the concentration-response curve for the tail moment in the SCG assay, MAs(III) and DMAs(III) were 77 and 386 times more potent than iAs(III), respectively. Because methylated trivalent arsenicals were the only arsenic compounds that were observed to damage naked DNA and required no exogenously added enzymatic or chemical activation systems, they are considered here to be direct-acting forms of arsenic that are genotoxic, though they are not, necessarily, the only genotoxic species of arsenic that could exist.

Arsenic↗
PubMed2003

Arsenic methylation and bladder cancer risk in Taiwan.

OBJECTIVE: The mechanism of arsenic detoxification in humans remains unclear. Data are especially lacking for low-level arsenic exposure. We hypothesize that arsenic methylation ability, defined as the ratios of monomethylarsonic acid (MMA(V))/inorganic arsenic (primary arsenic methylation index, PMI) and dimethylarsinic acid (DMA(V))/ MMA(V) (secondary arsenic methylation index, SMI), may modify the association between cumulative arsenic exposure (CAE, mg/L-year) and the risk of bladder cancer. In this study we investigated the relationship among arsenic methylation ability, CAE, and the risk of bladder cancer in a hospital-based case-control study in southwestern Taiwan. METHODS: From January 1996 to December 1999 we identified 49 patients with newly diagnosed cases of bladder cancer at the National Cheng-Kung University (NCKU) Medical Center; controls consisted of 224 fracture and cataract patients selected from the same medical center. The levels of four urinary arsenic species: arsenite (As(III)), arsenate (As(V)), MMA(V), and DMA(V)) were determined in all subjects by using the high-performance liquid chromatography hydride-generation atomic absorption spectrometry (HPLC-HGAAS). CAE was estimated by using published data collected in a survey from 1974 to 1976. RESULTS: Compared to a CAE < or = 2 mg/L-year, CAE > 12 mg/L-year was associated with an increased risk of bladder cancer (multivariate odds ratio (OR) 4.23, 95% confidence interval (CI) 1.12-16.01), in the setting of a low SMI (< or = 4.8). Compared to women, smoking men (OR 6.23, 95% CI 1.88-20.62) and non-smoking men (OR 3.25, 95% CI 0.95-11.06) had higher risks of bladder cancer. Given the same level of PMI, smoking men (OR 9.80, 95% CI 2.40-40.10) and non-smoking men (OR 4.45, 95% CI 1.00-19.84) had a higher risk of bladder cancer when compared to women. With the same level of SMI, both smoking men (OR 6.28, 95% CI 1.76-22.39) and non-smoking men (OR 3.31, 95% CI 0.84-12.97) had a higher risk of bladder cancer when compared to women. CONCLUSIONS: Subjects with low SMI have a substantially increased risk of bladder cancer, especially when combined with high CAE levels.

Aged↗
PubMed2004

Risk assessment on renal dysfunction caused by co-exposure to arsenic and cadmium using benchmark dose calculation in a Chinese population.

Arsenic and cadmium are important inorganic toxicants in the environment. Humans certainly have the potential to be exposed to the mixtures of arsenic and cadmium, but the toxicological interactions of these inorganic mixtures are poorly defined. A general population co-exposed to arsenic and cadmium, was selected in China. The total number of participants was 245, made up of 122 in the arsenic-cadmium polluted area, 123 in the non polluted area. Urinary arsenic (UAs) and cadmium (UCd) were determined by atomic absorption spectrometry as exposure biomarkers and beta2-microglobulin (Ubeta2MG), albumin (UALB), N-acetyl-beta2-glucosaminidase (UNAG) in urine were determined as effect biomarkers. The benchmark dose (BMD) and the lower confidence limit on the benchmark dose (LBMD) were calculated to estimate the critical concentration of UAs and UCd. UAs and UCd concentrations in the polluted area were significantly higher than those in the non polluted area (P < 0.01). The levels of Ubeta2MG, UALB and UNAG in the polluted area were significantly higher than those in the non polluted area (P < 0.01). The BMD/LBMD of UAs and UCd for a 10% level of risk above the background level were estimated as 121.91/102.11 microg/g creatinine and 1.05/0.88 microg/g creatinine. It was suggested that the lower confidence limit of population critical concentration of UAs and UCd for renal dysfunction for 10% excess risk level above the background, which is obtained from LBMD, may need to be kept below 102 and 0.88 microg/g creatinine in order to prevent renal damage in general population co-exposed to arsenic and cadmium. It is indicated that combined effect of arsenic and cadmium were additive effect and/or synergistic effect, and cadmium may potentiate arsenic nephrotoxicity during the long-term and co-exposure to arsenic and cadmium in humans.

Acetylglucosaminidase↗
PubMed2001

Role of metabolism in arsenic toxicity.

In humans, as in most mammalian species, inorganic arsenic is methylated to methylarsonic acid (MMA) and dimethylarsinic acid (DMA) by alternating reduction of pentavalent arsenic to trivalent and addition of a methyl group from S-adenosylmethionine. The methylation of inorganic arsenic may be considered a detoxification mechanism, as the end metabolites, MMA and DMA, are less reactive with tissue constituents, less toxic, and more readily excreted in the urine than is inorganic arsenic, especially the trivalent form (AsIII, arsenite). The latter is highly reactive with tissue components, due to its strong affinity for sulfhydryl groups. Thus, following exposure to AsV the first step in the biotransformation, i.e. the reduction to AsIII, may be considered a bioactivation. Also, reactive intermediate metabolites of high toxicity, mainly MMAIII, may be formed and distributed to tissues. Low levels of MMAIII and DMAIII have been detected in urine of individuals chronically exposed to inorganic arsenic via drinking water. However, the contribution of MMAIIIand DMAIII to the toxicity observed after intake of inorganic arsenic by humans remains to be elucidated. The major route of excretion of arsenic is via the kidneys. Evaluation of the methylation of arsenic is mainly based on the relative amounts of the different metabolites in urine. On average human urine contains 10-30% inorganic arsenic, 10-20% MMA and 60-80% DMA.

Animals↗
PubMed2006

Comparison of health effects between individuals with and without skin lesions in the population exposed to arsenic through drinking water in West Bengal, India.

A study was conducted to explore the effect of arsenic causing conjunctivitis, neuropathy and respiratory illness in individuals, with or without skin lesions, as a result of exposure through drinking water, contaminated with arsenic to similar extent. Exposed study population belongs to the districts of North 24 Parganas and Nadia, West Bengal, India. A total of 725 exposed (373 with skin lesions and 352 without skin lesions) and 389 unexposed individuals were recruited as study participants. Participants were clinically examined and interviewed. Arsenic content in drinking water, urine, nail and hair was estimated. Individuals with skin lesion showed significant retention of arsenic in nail and hair and lower amount of urinary arsenic compared to the group without any skin lesion. Individuals with skin lesion also showed higher risk for conjunctivitis ((odd's ratio) OR: 7.33, 95% CI: 5.05-10.59), peripheral neuropathy (OR: 3.95, 95% CI: 2.61-5.93) and respiratory illness (OR: 4.86, 95% CI: 3.16-7.48) compared to the group without any skin lesion. The trend test for OR of the three diseases in three groups was found to be statistically significant. Again, individuals without skin lesion in the exposed group showed higher risk for conjunctivitis (OR: 4.66, 95% CI: 2.45-8.85), neuropathy (OR: 3.99, 95% CI: 1.95-8.09), and respiratory illness (OR: 3.21, 95% CI: 1.65-6.26) when compared to arsenic unexposed individuals. Although individuals with skin lesions were more susceptible to arsenic-induced toxicity, individuals without skin lesions were also subclinically affected and are also susceptible to arsenic-induced toxicity and carcinogenicity when compared to individuals not exposed to arsenic.

Adolescent↗
PubMed2004

Arsenic induces human keratinocyte apoptosis by the FAS/FAS ligand pathway, which correlates with alterations in nuclear factor-kappa B and activator protein-1 activity.

Epidemiologic studies demonstrated that long-term exposure to arsenic induces arsenical skin cancers, including Bowen's disease. Immunohistochemically, Bowen's disease shows proliferating and apoptotic characteristics. The transcription factors nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1) functionally regulate cell proliferation, transformation, and apoptosis. To investigate the mechanism of arsenic-induced apoptosis and related alterations in NF-kappa B and AP-1 activity, we exposed cultured human foreskin keratinocytes to different concentrations of sodium arsenite. At lower concentrations (< or =1 microM), arsenic induced keratinocyte proliferation and enhanced both NF-kappa B and AP-1 activity. At higher concentrations (> or =5 microM), arsenic induced keratinocyte apoptosis by the Fas/Fas ligand (FasL) pathway. At apoptosis induction concentrations, NF-kappa B activity was not enhanced; however, AP-1 activity was further enhanced. These results indicated that upregulation of NF-kappa B at lower arsenic concentrations was correlated with keratinocyte proliferation. In contrast, higher concentrations of arsenic enhanced AP-1 and induced Fas/FasL-associated apoptosis. The concentration-dependent arsenic effects on transcription factors activity can help to clarify the mechanisms in arsenic-induced proliferation and apoptosis in keratinocytes.

Adult↗
PubMed2002

Arsenic induces tumor necrosis factor alpha release and tumor necrosis factor receptor 1 signaling in T helper cell apoptosis.

Long-term exposure to arsenic induces arsenical cancers in human beings. Arsenic has been shown to induce apoptosis in a variety of cell systems. Previous studies revealed that patients with arsenic-induced Bowen's disease showed a defective cell-mediated immunity and decreased percentages of T cell and T helper cell subpopulations in peripheral mononuclear cells. The purpose of this study was to investigate the effects of arsenic on T cell survival and function in mononuclear cells. Arsenic concentrations higher than 1 micro M induced tumor necrosis factor alpha release from mononuclear cells and caused a cytotoxic effect on T cells. When exposed to higher concentrations of arsenic, apoptosis was induced. CD4+ cells were the major apoptoic population in mononuclear cells. Tumor necrosis factor receptor 1 expression on CD4+ cells, but not Fas/FasL, was significantly enhanced by arsenic treatment compared to other mononuclear cells. Increased expressions of tumor necrosis factor receptor 1 related death domain proteins and activated caspases were observed. These findings indicate that tumor necrosis factor receptor 1 signaling is the major pathway in arsenic-induced T helper cell apoptosis.

Adult↗
PubMed1996

The role of arsenic-thiol interactions in metalloregulation of the ars operon.

The ars operon of the Escherichia coli plasmid R773 that confers arsenical and antimonial resistance is negatively regulated by the ArsR repressor. ArsR residues Cys-32 and Cys-34 were previously identified as involved in induction by arsenite and antimonite, suggesting coordination between As(III) and the two cysteine thiolates. However, in small molecule thiolate-As(III) complexes, arsenic is frequently three-coordinate. A site-directed mutagenic approach was employed in a search for a third arsenic ligand. ArsR proteins with C32G, C34G, and C32G/C34G substitutions were active repressors, but were not inducible in vivo. In vitro, the altered repressor-ars DNA complexes could not be dissociated by inducers. Alteration of Cys-37 and Ser-43, residues located in or near the putative helix-turn-helix DNA-binding region of the protein, had no effect on the inducibility of the operon. While these results indicated that neither the thiolate of Cys-37 nor the hydroxyl oxygen of Ser-43 is required for induction, they did not eliminate either atom as a potential arsenic ligand. Another approach involved reaction with an alternative inducer, phenylarsine oxide, which can form only two coordinations. Phenylarsine oxide was shown to be as effective as or more effective than arsenite or antimonite in induction in vivo. In vitro, the organic arsenical was more effective than either arsenite or antimonite in dissociating the repressor-promoter complex. Thus, two ArsR-arsenic bonds are sufficient for induction. The interaction of ArsR proteins with As(III) was examined using a phenylarsine oxide affinity resin. ArsR proteins containing any two of the three cysteine residues Cys-32, Cys-34, and Cys-37 bound to the resin. Alteration of any two of the three resulted in loss of binding. Arsenic X-ray absorption spectroscopy of ArsR treated stoichiometrically with arsenite confirmed the average arsenic coordination as AsS3 These results suggest that all three cysteine thiolates are arsenic ligands, but binding to only two, the Cys-32 and Cys-34 thiolates, is required to produce the conformational change that results in release of the repressor from the DNA and induction.

Amino Acid Sequence↗
PubMed2003

Oxidative stress contributes to arsenic-induced telomere attrition, chromosome instability, and apoptosis.

The environmental contaminant arsenic causes cancer, developmental retardation, and other degenerative diseases and, thus, is a serious health concern worldwide. Paradoxically, arsenic also may serve as an anti-tumor therapy, although the mechanisms of its antineoplastic effects remain unclear. Arsenic exerts its toxicity in part by generating reactive oxygen species. We show that arsenic-induced oxidative stress promotes telomere attrition, chromosome end-to-end fusions, and apoptotic cell death. An antioxidant, N-acetylcysteine, effectively prevents arsenic-induced oxidative stress, telomere erosion, chromosome instability, and apoptosis, suggesting that increasing the intracellular antioxidant level may have preventive or therapeutic effects in arsenic-induced chromosome instability and genotoxicity. Embryos with shortened telomeres from late generation telomerase-deficient mice exhibit increased sensitivity to arsenic-induced oxidative damage, suggesting that telomere attrition mediates arsenic-induced apoptosis. Unexpectedly, arsenite did not cause chromosome end-to-end fusions in telomerase RNA knockout mouse embryos despite progressively damaged telomeres and disrupting embryo viability. Together, these findings may explain why arsenic can initiate oxidative stress and telomere erosion, leading to apoptosis and anti-tumor therapy on the one hand and chromosome instability and carcinogenesis on the other.

Acetylcysteine↗
PubMed2006

Arsenic induces NAD(P)H-quinone oxidoreductase I by disrupting the Nrf2 x Keap1 x Cul3 complex and recruiting Nrf2 x Maf to the antioxidant response element enhancer.

The ubiquitous toxic metalloid arsenic elicits pleiotropic adverse and adaptive responses in mammalian species. The biological targets of arsenic are largely unknown at present. We analyzed the signaling pathway for induction of detoxification gene NAD(P)H-quinone oxidoreductase (Nqo1) by arsenic. Genetic and biochemical evidence revealed that induction required cap 'n' collar basic leucine zipper transcription factor Nrf2 and the antioxidant response element (ARE) of Nqo1. Arsenic stabilized Nrf2 protein, extending the t(1/2) of Nrf2 from 21 to 200 min by inhibiting the Keap1 x Cul3-dependent ubiquitination and proteasomal turnover of Nrf2. Arsenic markedly inhibited the ubiquitination of Nrf2 but did not disrupt the Nrf2 x Keap1 x Cul3 association in the cytoplasm. In the nucleus, arsenic, but not phenolic antioxidant tert-butylhydroquinone, dissociated Nrf2 from Keap1 and Cul3 followed by dimerization of Nrf2 with a Maf protein (Maf G/Maf K). Chromatin immunoprecipitation demonstrated that Nrf2 and Maf associated with the endogenous Nqo1 ARE enhancer constitutively. Arsenic substantially increased the ARE occupancy by Nrf2 and Maf. In addition, Keap1 was shown to be ubiquitinated in the cytoplasm and deubiquitinated in the nucleus in the presence of arsenic without changing the protein level, implicating nuclear-cytoplasmic recycling of Keap1. Our data reveal that arsenic activates the Nrf2/Keap1 signaling pathway through a distinct mechanism from that by antioxidants and suggest an "on-switch" model of Nqo1 transcription in which the binding of Nrf2 x Maf to ARE controls both the basal and inducible expression of Nqo1.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Arsenic in breast milk during the first 3 months of lactation.

Increased concentrations of arsenic were found in soil and ground water from a military training area in Munster, Lower Saxony, Germany, where chemical weapons were dumped after World War II. In order to assess the possible impact of this contamination for nursing new-borns and infants, samples from breast milk of 36 women were analysed with respect to arsenic content. Study participants came from three different regions: the city of Hamburg, the rural area of Soltau, Lower Saxony, and from Munster, the potentially contaminated area. Breast milk samples were collected immediately before and after nursing on days 2, 5, 15, 30, 45, 60, 75, and 90 post partum. At least 10 ml were required for measurements of arsenic, and 187 samples were of that volume. Samples were analysed with a Perkin-Elmer Type 403 hydride-generation atomic absorption spectrometer, equipped with an arsenic EDL-lamp. Arsenic was not detectable, i.e. below 0.3 microgram/l, in 154 of 187 samples. The highest concentration of 2.8 micrograms/l was measured in a sample from the rural area of Soltau. Geometric means of arsenic concentrations were comparable in the three regions. Concentrations did neither differ in samples obtained before and after nursing nor with respect to age of the infant. The calculated daily intake of arsenic was in the range of 0.02 to 0.06 microgram per kg body weight, which is far below the lower limit of daily permissible intake for adults (WHO/JECFA recommendation 1993) of 15 micrograms/kg/wk. In conclusion, we found concentrations of arsenic in breast milk within the reported safety limits. This was also true for samples from women living in a region which has previously been shown to be contaminated with arsenic from chemical weapons.

Adult↗