Showing papers on "Sodium arsenite published in 2006"
TL;DR: The results indicate that arsenic causes testicular toxicity by germ cell degeneration and inhibits androgen production in adult male rats probably by affecting pituitary gonadotrophins.
Abstract: Background
Inorganic arsenic is a major water pollutant and a known human carcinogen that has a suppressive influence on spermatogenesis and androgenesis in male reproductive system. However, the actual molecular events resulting in male reproductive dysfunctions from exposure to arsenic remain unclear. In this context, we evaluated the mode of action of chronic oral exposure of sodium arsenite on hypothalamo-pituitary- testicular activities in mature male albino rats.
281 citations
TL;DR: It was interesting to observe that during combined exposure the toxic effects were less pronounced compared to the effects of arsenic or fluoride alone, and in some cases antagonistic effects were noted following co-exposure to arsenic and fluoride.
132 citations
TL;DR: The results represent an attempt to establish an animal model for in vivo studies of diabetogenic effects of chronic arsenic exposure and the levels of total glutathione and lipoperoxidation in pancreas increased significantly relative to the control group indicating the presence of stress and oxidative damage.
115 citations
TL;DR: The present study demonstrates the effect of acute arsenic administration at three different doses in liver and brain of Wistar rats and observed significant changes in lipid peroxidation and glutathione peroxidase activity, as well as dose-dependent histopathological changes.
Abstract: Arsenic is a well established human carcinogen and is ubiquitous in the environment. The present study demonstrates the effect of acute arsenic administration at three different doses in liver and brain of Wistar rats. Sodium arsenite was administered orally at doses of 6.3 mg/kg, 10.5 mg/kg and 12.6 mg/kg of body weight on the basis of a lethal dose 50% (LD50) for 24 hr. After administration of arsenites, liver and brain were analyzed for various parameters of oxidative stress, histopathological changes and caspase-3 activity. Glutathione levels were decreased significantly in the liver at all doses. In liver the following biochemical changes were observed, a significant lipid peroxidation and cytochrome-P450 induction along with significant decrease in catalase and superoxide dismutase was observed at 10.5 mg/kg and 12.6 mg/kg. The activity of glutathione peroxidase was increased significantly at all doses. In brain, no significant change was observed at 6.3 mg/kg. However, a significant increase in lipid peroxidation and glutathione peroxidase activity along with significant decrease in the activity of glutathione, catalase and superoxide dismutase was observed at 10.5 mg/kg and 12.6 mg/kg. The activity of glutathione-S-transferase was decreased significantly in both liver and brain at 10.5 and 12.6 mg/kg. No significant alteration in the activity of glucose-6-phosphate dehydrogenase and glutathione reductase was observed in either liver or brain at any dose. Dose-dependent histopathological changes, observed in both liver and brain are also described. A significant increase in caspase-3 activity was observed at all doses in liver and at 10.5 and 12.6 mg/kg in brain. Sodium arsenite caused DNA cleavage into fragments and manifested as “DNA laddering”, a hallmark of apoptosis.
112 citations
TL;DR: The data suggest that arsenic may contribute to the development of diabetes mellitus by impairing pancreatic β-cell functions, particularly insulin synthesis and secretion.
100 citations
TL;DR: Aerial parts (shoots) of maize seedlings fed hydroponically with 300 μM sodium arsenate or 250 h were analyzed for differentially expressed proteins by 2‐DE and digital image analysis and 7 proteins were identified that were completely repressed by As(V) and/or As(III), except protein kinase C inhibitor, which was newly detected after exposure to As( V).
Abstract: Aerial parts (shoots) of maize seedlings fed hydroponically with 300 muM sodium arsenate [As(V)] or 250 muM sodium arsenite [As(III)] for 24 h were analyzed for differentially expressed proteins by 2-DE and digital image analysis. About 15% of total detected proteins (74 out of 500) were up- or, mainly, down-regulated by arsenic, among which 14 were selected as being those most affected by the metalloid. These proteins were analyzed by MALDI-TOF MS and 7 of them were identified: translation initiation factor eIF-5A, ATP synthase, cysteine synthase, malate dehydrogenase, protein kinase C inhibitor, Tn10 transposase-like protein, and guanine nucleotide binding protein. Each of these proteins was completely repressed by As(V) and/or As(III), except protein kinase C inhibitor, which was newly detected after exposure to As(V).
90 citations
TL;DR: Results suggest that oxidative damage may be the main mechanism of toxicity induced by exposure of the peripheral nervous system to arsenite and that such damage could be attenuated by alpha-TOC-supplementation.
Abstract: Inorganic arsenic (iAs) exposure causes peripheral neuropathy. Oxidative effects caused by iAs exposure in peripheral nerves have been incompletely characterized. This study analyzed arsenic and lipid oxidative damage in the brain, spinal cord, and sciatic and sensory sural nerves following arsenite exposure. This study also explored whether alpha tocopherol (α-TOC) administration mitigates arsenite-induced oxidative damage. Thiobarbituric acid-reactive substance (TBARS) levels and distributions of iAs and its metabolites were evaluated in male Wistar rats following 30 d of sodium arsenite exposure (10 mg/kg bodyweight (bw)/d, by gavage). A second group also received α-TOC (125 mg/kg bw/d, by gavage) during the final 20 d of arsenite administration. Arsenite exposure caused increased TBARS levels within each region of the nervous system; oxidative stress was most pronounced in the sural and sciatic nerves. In addition there was a positive quadratic relationship between TBARS levels and the concentration of arsenicals found in the nervous system (r2 = 0.878, p
74 citations
TL;DR: Enhanced expression of MRP2 and lower expression of AQP3 are responsible for lower arsenic accumulation in arsenic-resistant R15 cells, which is suggested to be due to higher efflux and/or lower uptake of As(III).
74 citations
TL;DR: Distribution of inorganic arsenic and its metabolites, methyl arsenic and dimethyl arsenic, were determined in maternal and fetal tissues collected on gestational day 18 of exposure regimens, suggesting that a high tissue burden of arsenic affected formation or retention of methylated species in this organ.
66 citations
TL;DR: Chronic arsenic administration induces a specific pattern of apoptosis called post-mitotic apoptosis, which is suggestive of arsenic induced oxidative stress.
64 citations
TL;DR: Concomitant administration of zinc with arsenic showed remarkable protection against blood delta-aminolevulinic acid dehydratase (ALAD) activity as well as providing protection to hepatic biochemical variables indicative of oxidative stress and tissue injury.
TL;DR: The results indicate that the chemical agents that had a positive response in the present study are potentially genotoxic to mammalian cells.
Abstract: To assess the genotoxicity of 14 chemical agents used as locally applied agents in dental practice, the ability of these agents to elicit chromosome aberrations was examined using Syrian hamster embryo (SHE) cells. Chromosome aberrations in SHE cells were induced by treatment with three of eight chemical agents used as endodontic medicaments, i.e. ethylenediaminetetraacetic acid (EDTA), formocresol (a mixture of formalin and tricresol), and sodium arsenite. The other five chemical agents, i.e. chloramphenicol, p-chlorophenol, p-phenolsulfonic acid, sodium hypochlorite, and tetracycline hydrochloride exhibited a negative response for chromosome aberrations. Assessment of three dyes used for disclosing dental plaque showed chromosome aberrations induced by basic fuchsin but not by acid fuchsin and erythrosine B. Three local anesthetics, lidocaine hydrochloride, prilocaine hydrochloride, and procaine hydrochloride, were negative for chromosome aberrations. Among the ten chemical agents that exhibited a negative response in the assay, p-chlorophenol, sodium hypochlorite, and erythrosine B induced chromosome aberrations in SHE cells when treated in the presence of exogenous metabolic activation. The percentages of cells with polyploidy or endoreduplication were enhanced by formocresol, sodium arsenite, p-chlorophenol, p-phenolsulfonic acid, sodium hypochlorite, erythrosine B, prilocaine hydrochloride, and procaine hydrochloride in the absence or presence of exogenous metabolic activation. Our results indicate that the chemical agents that had a positive response in the present study are potentially genotoxic to mammalian cells.
TL;DR: IFN-gamma can protect against NaAs-induced acute renal injury, probably by maintaining Nrf2-mediated intrarenal MRP1 gene expression.
Abstract: Subcutaneous injection of sodium arsenite (NaAs, 12.5 mg/kg) into BALB/c [wild-type (WT)] mice causes acute renal dysfunction characterized by severe hemorrhages, acute tubular necrosis, and cast formation, with increases in serum blood urea nitrogen and creatinine levels. Concomitant enhancement in intrarenal interferon (IFN)-γ expression prompted us to examine its roles in this pathology. IFN-γ-deficient (IFN-γ−/−) mice exhibited higher serum blood urea nitrogen and creatinine levels and exaggerated histopathological changes, compared with WT mice. Eventually, IFN-γ−/− mice exhibited a high mortality (87.5%) within 24 hours after NaAs challenge, whereas most WT mice survived. The intrarenal arsenic concentration was significantly higher in IFN-γ−/− mice later than 10 hours after NaAs treatment, with attenuated intrarenal expression of multidrug resistance-associated protein (MRP) 1, a main transporter for NaAs efflux, compared with WT mice. NF-E2-related factor (Nrf) 2 protein, a transcription factor crucial for MRP1 gene expression, was similarly increased in the kidneys of both strains of mice after NaAs treatment. In contrast, the absence of IFN-γ augmented transforming growth factor-β-Smad3 signal pathway and eventually enhanced the expression of activating transcription factor 3, which is presumed to repress Nrf2-mediated MRP1 gene expression. Thus, IFN-γ can protect against NaAs-induced acute renal injury, probably by maintaining Nrf2-mediated intrarenal MRP1 gene expression.
TL;DR: It is demonstrated that arsenic not only inhibited the TCDD-induced CYP1A1 activation but also interfered with DRE-CALUX bioassay in human hepatoma cells, suggesting that extensive cleanup of sample for removal of any possible interfering factor is critical to guarantee the accuracy of dioxin-TEQ levels using DRE.
TL;DR: Data suggest that the pro-angiogenesis effect of arsenic is initiated at the plasma membrane integrin alphavbeta3, involves activation of the ERK1/2 pathway and is effectively reversed by various selenium-derived compounds.
Abstract: Inorganic arsenic (arsenite and arsenate) in drinking water hasbeen associated with skin cancers and increased incidence of car-diovascular diseases. Additionally, studies have demonstrated thepro-angiogenic effect of arsenite and its potential promotion oftumor angiogenesis and tumor progression. Furthermore, recentreports demonstrated reversal of skin co-carcinogenesis by anorganoselenium compound. The present study was undertakento determine the effect and mechanism on angiogenesis of arseniteat low level and its potential reversal by various selenium-derivedcompounds. The pro-angiogenesis effects and mechanisms of so-dium arsenite were determined using the chick chorioallantoicmembrane (CAM) model over 3 days and compared with stan-dard pro-angiogenesis factors, such as basic fibroblast growthfactor (b-FGF). Additionally, the potential effect of various sele-nium-derived compounds—such as dimethyl selenone, diphenylselenone, sodium selenite or Se-methyl selenocysteine—in revers-ing the pro-angiogenesis effect of arsenite or b-FGF was alsodetermined in the CAM model. The pro-angiogenesis effect ofarsenite or b-FGF was significantly (P , 0.01) blocked by di-methyl selenone, diphenyl selenone, sodium selenite or Se-methylselenocysteine. The pro-angiogenesis effect of either sodium arse-nite at 33 nM or b-FGF was blocked (P,0.01) by the extracellularsignal-regulated kinases 1 and 2 (ERK1/2) activation inhibitor, PD98059. Additionally, the pro-angiogenic effect of arsenic or b-FGFwas blocked as well (P , 0.01) by the avb3 antagonist, XT199.These data suggest that the pro-angiogenesis effect of arsenic isinitiated at the plasma membrane integrin avb3, involves activa-tion of the ERK1/2 pathway and is effectively reversed by variousselenium-derived compounds.IntroductionArsenic, an element that is found both in native and in combined form,has been used medicinally for over 2400 years. In the 19th century, itwas the mainstay of the materia medica. A solution of potassiumarsenite (Fowler’s solution) was used for a variety of systemic ill-nesses from the 18th until the 20th century. This multipurpose solu-tion was also the primary therapy for the treatment of chronicmyelogenous leukemia until it was replaced by radiation and cyto-toxic chemotherapy. The past 100 years have seen a precipitous de-cline in arsenic use; by the mid-1990s, the only recognized indicationwas the treatment of trypanosomiasis. Much of this decline was due toconcerns about the toxicity and potential carcinogenicity of chronicarsenic administration (1). Chinese physicians had been using arsenic-containing medicines, including arsenic trioxide, as part of a treatmentfor acute promyelocytic leukemia (APL). Their accumulated experi-ence showed that a stable solution of arsenic trioxide given by in-travenous infusion was remarkably effective both in patients withnewly diagnosed APL and in those with refractory and relapsedAPL (2). The mechanisms of action of arsenic derivatives in thisdisease and other malignancies are many and include induction ofapoptosis, inhibition of proliferation and inhibition of angiogenesis(2). Molecular studies and ongoing clinical trials suggest that, asa chemotherapeutic agent, arsenic trioxide shows great promise inthe treatment of malignant diseases (2).Arsenic trioxide can inhibit proliferation and induce apoptosis inmultiple myeloma cells in vitro and in vivo (3). However, low con-centrations of arsenic trioxide stimulate vascular cell proliferation incell culture and angiogenesis in vivo (4,5). Arsenite was shown tocause dose-dependent increase in vessel density in the chick chorio-allantoic membrane (CAM) assay (5). The threshold arsenic trioxideconcentration for this response was 0.033 lM, and inhibition of vesselgrowth was observed at concentrations .1 lM (5). Hence, arsenitemight have carcinogenic effect at low levels of exposure, which mightbe accelerated by its pro-angiogenesis effects.Data supported a potential anti-angiogenic effect of selenium inthe chemoprevention of cancer (6,7). With regard to tumor angio-genesis, the chemopreventive effect of increased selenium intake onchemically induced mammary carcinogenesis has been associatedwith reduced intratumoral microvessel density (6). Control of an-giogenesis is a complex process involving local release of vasculargrowth factors, the extracellular matrix, adhesion molecules andmetabolic factors (7–9). Mechanical forces within blood vesselsmay also play a role (7). The principal endogenous growth factorsimplicated in new blood vessel growth are the fibroblast growthfactor (FGF) family and vascular endothelial growth factor (VEGF)(10). The mitogen-activated protein kinase (MAPK) signal trans-duction cascade (extracellular signal-regulated kinases 1 and 2[ERK1/2]) is known to be involved both in VEGF gene expressionand in control of proliferation of vascular endothelial cells (10). Theavailability of a chick CAM model of angiogenesis (10–14) allowedus to define the effect of low levels of sodium arsenite and its po-tential mechanism of actions.In this report, we describe a pro-angiogenesis effect of arsenic tri-oxide that is comparable with that of basic FGF (b-FGF) or VEGF inthe CAM model. We also provide evidence that representative sele-nium compounds reverse the pro-angiogenesis effect of arsenic,which is initiated at the endothelial cell plasma membrane, involvesa plasma membrane integrin avb3 receptor and is mediated by acti-vation of the ERK1/2 signal transduction pathway.Materials and methods
TL;DR: It is suggested that melatonin acts as a protective agent against arsenic-induced cellular oxidative stress.
Abstract: The effects of melatonin on arsenic-induced changes on cellular antioxidant system were studied in male rats of the Wistar strain. Arsenic treatment (i.p. as sodium arsenite) was done at a dose of 5.55 mg/kg body weight (equivalent to 35% of LD50) per day for a period of 30 days, while melatonin supplementation (i.p.) was performed at a dose of 10 mg/kg body weight per day for the last 5 days prior to sacrifice. Melatonin supplementation reversed the arsenic-mediated changes in reduced glutathione (GSH) level and lipid peroxidation in liver and kidney. Arsenic-induced decreased glutathione reductase activity in liver and increased activity in kidney was appreciably counteracted by melatonin. Melatonin also inhibited arsenic-induced free hydroxyl radical production in the tissues. The decreased superoxide dismutase (SOD) activity in liver and kidney and that of catalase in liver due to arsenic treatment were also counteracted by melatonin. It is suggested that melatonin acts as a protective agent against arsenic-induced cellular oxidative stress.
TL;DR: The data suggest that arsenic may contribute to the development of diabetes mellitus by impairing pancreatic beta-cell functions, particularly insulin synthesis and secretion.
Abstract: Human studies have shown that chronic inorganic arsenic (iAs) exposure is associated with a high prevalence and incidence of type 2 diabetes. However, the mechanism(s) underlying this effect are not well understood, and practically, there is no information available on the effects of arsenic on pancreatic beta-cells functions. Thus, since insulin secreted by the pancreas plays a crucial role in maintaining glucose homeostasis, our aim was to determine if sodium arsenite impairs insulin secretion and mRNA expression in single adult rat pancreatic beta-cells. Cells were treated with 0.5, 1, 2, 5 and 10 microM sodium arsenite and incubated for 72 and 144 h. The highest dose tested (10 microM) decreased beta-cell viability, by 33% and 83%, respectively. Insulin secretion and mRNA expression were evaluated in the presence of 1 and 5 microM sodium arsenite. Basal insulin secretion, in 5.6 mM glucose, was not significantly affected by 1 or 5 microM treatment for 72 h, but basal secretion was reduced when cells were exposed to 5 microM sodium arsenite for 144 h. On the other hand, insulin secretion in response to 15.6 mM glucose decreased with sodium arsenite in a dose-dependent manner in such a way that cells were no longer able to distinguish between different glucose concentrations. We also showed a significant decrease in insulin mRNA expression of cells exposed to 5 microM sodium arsenite during 72 h. Our data suggest that arsenic may contribute to the development of diabetes mellitus by impairing pancreatic beta-cell functions, particularly insulin synthesis and secretion.
01 Jan 2006
TL;DR: It was found that survivin was overexpressed in ATL, especially in acute-type ATL, and sodium arsenite was shown to down-regulate the expression of survivin through the NF-kappaB pathway, thus inhibiting cell growth and promoting apoptosis of ATL cells.
Abstract: Patients with acute- or lymphoma-type adult T-cell leukemia (ATL) have a poor outcome because of the intrinsic drug resistance to chemotherapy. Protection from apoptosis is a common feature involved in multidrug-resistance of ATL. IAP (inhibitor of apoptosis) family proteins inhibit apoptosis induced by a variety of stimuli. In this study, we investigated the expression of IAP family members (survivin, cIAP1, cIAP2, and XIAP) in the primary leukemic cells from patients with ATL. We found that survivin was overexpressed in ATL, especially in acute-type ATL. Sodium arsenite was shown to down-regulate the expression of survivin at both the protein and RNA levels in a time- and dose-dependent manner, thus inhibiting cell growth, inducing apoptosis, and enhancing the caspase-3 activity in ATL cells. Nuclear factor-κB (NF-κB) enhances the transcriptional activity of survivin. Sodium arsenite suppressed the constitutive NF-κB activation by preventing the IκB-α degradation and the nuclear translocation of NF-κB. These findings suggest that survivin is an important antiapoptotic molecule that confers drug resistance on ATL cells. Sodium arsenite was shown to down-regulate the expression of survivin through the NF-κB pathway, thus inhibiting cell growth and promoting apoptosis of ATL cells.
TL;DR: Data support a role for perturbed cell cycle progression in As3+ mediated neurodevelopmental toxicity in embryonic primary rat midbrain neuroepithelial cells over 48 h.
TL;DR: In this article, the authors investigated the expression of IAP family members (Survivin, cIAP1, CIAP2, XIAP) in the primary leukemic cells from patients with acute-or lymphoma-type adult T-cell leukemia (ATL).
TL;DR: Sodium arsenite was able to induce both DNA-strand breaks and protein-DNA adducts in arsenic exposed MRC-5 cells, depending on the concentrations of arsenic salts tested.
TL;DR: It is highly suggestive that CAT gene expression and protein levels are affected by arsenic.
TL;DR: Electrophoretic mobility shift assays showed that arsenite stimulated binding of the transcription factors, AP1 and CREBP to their respective binding motifs within 3 days, which supports a mechanism of oncogenesis based on persistent upregulation of D type cyclins leading to a concomitant loss of G1/S checkpoint control.
TL;DR: D-MEKK1, the fly orthologue of mammalian MEKK4/MTK1, and Hemipterous/D-MKK7 mediates the activation of D-JNK by cadmium and arsenite, thus providing a simpler model system to study JNK signaling.
Abstract: The family of c-Jun NH2-terminal kinases (JNK) plays important roles in embryonic development and in cellular responses to stress. Toxic metals and their compounds are potent activators of JNK in mammalian cells. The mechanism of mammalian JNK activation by cadmium and sodium arsenite involves toxicant-induced oxidative stress. The study of mammalian signaling pathways to JNK is complicated by the significant degree of redundancy among upstream JNK regulators, especially at the level of JNK kinase kinases (JNKKK). Using Drosophila melanogaster S2 cells, we demonstrate here that cadmium and arsenite activate Drosophila JNK (D-JNK) via oxidative stress as well, thus providing a simpler model system to study JNK signaling. To elucidate the signaling pathways that lead to activation of D-JNK in response to cadmium or arsenite, we employed RNA interference (RNAi) to knock down thirteen upstream regulators of D-JNK, either singly or in combinations of up to seven at a time. D-MEKK1, the fly orthologue of mammalian MEKK4/MTK1, and Hemipterous/D-MKK7 mediates the activation of D-JNK by cadmium and arsenite.
TL;DR: Strong effects of sodium arsenite treatment on upregulation of TRAIL-mediated apoptosis in human and mouse melanomas are observed and AKT overactivation increased melanoma survival in cell culture and dramatically accelerated growth of melanoma transplant in vivo, highlighting a role of AKT suppression for effective anticancer treatment.
TL;DR: The therapeutic effect of arsenic is the induction of apoptosis by modulating the gene expression profile of pro- and anti-apoptotic genes including the wt1 gene, which is up-regulated in acute myeloid leukemia (AML) and a variety of leukemia cell lines.
Abstract: Arsenic trioxide (As2O3) induces remission in patients with acute promyelocytic leukemia (APL). To better understand molecular mechanisms of arsenic actions, this study investigated the effect of two different arsenic compounds on gene expression of apoptosis and cellular proliferation related genes. The Wilms' tumor gene (wt1) is up-regulated in acute myeloid leukemia (AML) and a variety of leukemia cell lines. The expression of wt1 in these cells is proposed to have an anti-apoptotic effect. HL-60 and K562 were treated with arsenic trioxide (As2O3) and sodium arsenite (NaAsO2) at concentrations between 0 - 10 microM for up to 48 h. The induction of apoptosis was accompanied by down-regulation of hTERT and wt1 mRNA and protein expression but up-regulation of par-4. Low concentrations of 0.1 microM arsenic induced expression of the anti-apoptotic bcl-2 gene in both cell lines HL-60 and K562. There were no major differences encountered between compounds. After arsenic treatment of the leukemia cell lines HL-60 and K562 the up-regulation of par-4 may contribute to the induction of apoptosis rather than down-regulation of bcl-2. The therapeutic effect of arsenic is the induction of apoptosis by modulating the gene expression profile of pro- and anti-apoptotic genes including the wt1 gene.
TL;DR: The results presented here indicate that relatively low concentrations of arsenic and cadmium, close to those occuring in nature, may interfere with radiation effects.
Abstract: In the field of radiation protection the combined exposure to radiation and other toxic agents is recognised as an important research area. To elucidate the basic mechanisms of simultaneous exposure, the interaction of the carcinogens and environmental toxicants cadmium and two arsenic compounds, arsenite and arsenic trioxide, in combination with gamma-radiation in human lymphoblastoid cells (TK6) were investigated. Gamma-radiation induced significant genotoxic effects such as micronuclei formation, DNA damage and apoptosis, whereas arsenic and cadmium had no significant effect on these indicators of cellular damage at non-toxic concentrations. However, in combination with gamma-radiation arsenic trioxide induced a more than additive apoptotic rate compared to the sum of the single effects. Here, the level of apoptotic cells was increased, in a dose-dependent way, up to two-fold compared to the irradiated control cells. Arsenite did not induce a significant additive effect at any of the concentrations or radiation doses tested. On the other hand, arsenic trioxide was less effective than arsenite in the induction of DNA protein cross-links. These data indicate that the two arsenic compounds interact through different pathways in the cell. Cadmium sulphate, like arsenite, had no significant effect on apoptosis in combination with gamma-radiation at low concentrations and, at high concentrations, even reduced the radiation-induced apoptosis. An additive effect on micronuclei induction was observed with 1muM cadmium sulphate with an increase of up to 80% compared to the irradiated control cells. Toxic concentrations of cadmium and arsenic trioxide seemed to reduce micronuclei induction. The results presented here indicate that relatively low concentrations of arsenic and cadmium, close to those occuring in nature, may interfere with radiation effects. Differences in action of the two arsenic compounds were identified.
TL;DR: Results indicate that in the cow, arsenic acid is absorbed and excreted rapidly in the urine, and there is little storage in the tissues, and these low levels are rapidly depleted in a feed-off period and represent ''transit'' rather than true storage arsenic.
Abstract: Results indicate that in the cow, arsenic acid is absorbed and excreted rapidly in the urine. As a result, there is little storage in the tissues, and these low levels are rapidly depleted in a feed-off period and represent ''transit'' rather than true storage arsenic. Preliminary studies show that this tissue-bound arsenic is entirely in the pentavalent form, and that there is no evidence that it is partially reduced to the trivalent form. At no time was there any arsenic excreted in the milk when fed arsenic acid, sodium arsenite, or cacodylic acid. The marked difference between the metabolism of arsenic in the rat and any other animal makes it necessary to revise present concepts of arsenic compounds as cumulative poisons. 8 references, 7 tables.
TL;DR: Results are promising with respect to the use of thiabendazole-containing pesticides as alternatives to currently used pesticides for control of esca in vines.
TL;DR: It is concluded that DNA-damaging effects of NaAsO2 cannot adequately be interpreted if the comet assay is not accompanied by separate analysis of early endpoints for induction of apoptosis.
Abstract: To assess genotoxic effects of sodium arsenite (NaAsO2) the single-cell gel electrophoresis (comet assay) had been conducted in various studies indicating genotoxicity. However, DNA fragmentation due to NaAsO2-induced apoptosis may constitute a bias in the interpretation of the results. Apoptotic cells can show typically large and diffuse comets, which are usually excluded during genotoxicity analysis. It is controversial whether there is a time-window in which the apoptotic process generates comets that would falsely be interpreted to be the result of genotoxic DNA damage. Therefore, we evaluated frequency histograms for single-cell measures of tail DNA (% DNA in comet tail) in 30-min intervals after incubation of mouse lymphoma L5178Y cells with sodium arsenite (NaAsO2). In parallel, we evaluated apoptosis by measuring annexin V-positive cells with flow cytometry, and visualized apoptotic cells on slides by Hoechst bisbenzimide 33258 staining. The first observed effect at 30 min after treatment was an increase in annexin V-positive cells. At about 60 min the number of cells with moderate DNA migration increased in the comet-assay analysis. After 90 min, an increase in the number of cells with high levels of DNA migration was observed, which resulted in a bimodal distribution of cells with moderate and high levels of DNA migration. Hoechst-stained apoptotic cells could only be observed at later times (> or = 120 min). This means that the treatment would have been considered to be genotoxic if analysed at 120 min even if the cells with high levels of DNA migration would have been excluded. The occurrence of annexin V-positive cells preceded the appearance of cells with moderate levels of DNA migration. We hypothesize that these cells were early apoptotic cells and not indicative of genotoxic damage. We conclude that DNA-damaging effects of NaAsO2 cannot adequately be interpreted if the comet assay is not accompanied by separate analysis of early endpoints for induction of apoptosis.